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The present review demonstrates the major tumor suppressor genes, including TP53, CDKN2A and SMAD4, associated with pancreatic cancer. Each genes role, prevalence and impact on tumor development and progression are analyzed, focusing on the intricate molecular landscape of pancreatic cancer. In addition, this review underscores the prognostic significance of specific mutations, such as loss of TP53, and explores some potential targeted therapies tailored to these molecular signatures. The findings highlight the importance of genomic analyses for risk assessment, early detection and the design of personalized treatment approaches in pancreatic cancer. Overall, this review provides a comprehensive analysis of the molecular intricacies of pancreatic tumors, paving the way for more effective and tailored therapeutic interventions.

Early cancer diagnosis strongly relies on finding appropriate materials for the detection of respected biomarkers. For the first time, we have theoretically investigated the capability of the MoSe2 monolayer to detect three lung cancer biomarkers, including hexanal, nonanal, and p-cresol. To this end, adsorption performance, bandgap alteration, and charge transfer of the MoSe2 monolayer upon exposure to the three biomarkers were studied using density functional theory. The results, in all cases, indicate that the charge transfer is from the monolayer to the adsorbed biomarkers, and the adsorption of biomarkers decreases the bandgap of the monolayer, approving the p-type sensing character of the MoSe2 monolayer. This is in complete agreement with the band structure analysis of the material and the previous reports in the literature. Our findings demonstrated the appropriate performance of the MoSe2 monolayer in terms of the physisorption of the lung cancer biomarkers and desirable recovery times in the desorption process. Further performance enhancement of MoSe2 as a lung cancer biosensor can be the subject of future studies. [ABSTRACT FROM AUTHOR]

In Burkitt's lymphoma (BL), Epstein–Barr virus-encoded microRNAs (EBV miRNAs) are emerging as crucial regulatory agents that impact cellular and viral gene regulation. This review investigates the multifaceted functions of EBV miRNAs in the pathogenesis of Burkitt lymphoma. EBV miRNAs regulate several cellular processes that are essential for BL development, such as apoptosis, immune evasion, and cellular proliferation. These small, non-coding RNAs target both viral and host mRNAs, finely adjusting the cellular environment to favor oncogenesis. Prominent miRNAs, such as BART (BamHI-A rightward transcript) and BHRF1 (BamHI fragment H rightward open reading frame 1), are emphasized for their roles in tumor growth and immune regulation. For example, BART miRNAs prevent apoptosis by suppressing pro-apoptotic proteins, whereas BHRF1 miRNAs promote viral latency and immunological evasion. Understanding the intricate connections among EBV miRNAs and their targets illuminates BL pathogenesis and suggests novel treatment approaches. Targeting EBV miRNAs or their specific pathways offers a feasible option for developing innovative therapies that aim to disrupt the carcinogenic processes initiated by these viral components. future studies should focus on precisely mapping miRNA‒target networks and developing miRNA-based diagnostic and therapeutic tools. This comprehensive article highlights the importance of EBV miRNAs in Burkitt lymphoma, indicating their potential as biomarkers and targets for innovative treatment strategies. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer is a public health issue and was the third leading cause of cancer-related death worldwide in 2022. Early diagnosis can improve prognosis, making screening a central part of colorectal cancer management. Blood-based screening, diagnosis and follow-up of colorectal cancer patients are possible with the study of cell-free circulating tumor DNA. This study aimed to identify novel DNA methylation biomarkers of colorectal cancer that can be used for the follow-up of patients with colorectal cancer. Methods: A DNA methylation profile was established in the Gene Expression Omnibus (GEO) database (n = 507) using bioinformatics analysis and subsequently confirmed using The Cancer Genome Atlas (TCGA) database (n = 348). The in silico profile was then validated on local tissue and cell-free DNA samples using methylation-specific digital PCR in colorectal cancer patients (n = 35) and healthy donors (n = 35). Results: The DNA methylation of COL25A1 and METAP1D was predicted to be a colorectal cancer biomarker by bioinformatics analysis (ROC AUC = 1, 95% CI [0.999–1]). The two biomarkers were confirmed with tissue samples, and the combination of COL25A1 and METAP1D yielded 49% sensitivity and 100% specificity for cell-free DNA. Conclusion: Bioinformatics analysis of public databases revealed COL25A1 and METAP1D DNA methylation as clinically applicable liquid biopsies DNA methylation biomarkers. The specificity implies an excellent positive predictive value for follow-up, and the high sensitivity and relative noninvasiveness of a blood-based test make these biomarkers compatible with colorectal cancer screening. However, the clinical impact of these biomarkers in colorectal cancer screening and follow-up needs to be established in further prospective studies. [ABSTRACT FROM AUTHOR]

Objective To observe the effects of transarterial chemoembolization (TACE) combined with radiofrequency ablation (RFA) on tumor-associated serum biomarkers in patients with primary hepato- cellular carcinoma, aiming to provide a scientific reference for the treatment of related clinical diseases. Methods Using a random number table method, 78 patients with primary hepatocellular carcinoma treated from February 2019 to February 2021 were divided into the control group (39 patients, treated with TACE) and the combined group (39 patients, treated with TACE-RFA). The short-term efficacy, related serum biomarkers [serum E-cadherin (EC), alpha-fetoprotein (AFP), matrix metallopeptidase-9 (MMP-9), vascular endothelial growth factor (VEGF), alanine aminotransferase (ALT), total bilirubin (TBIL), gamma-glutamyl transferase (GGT), and carbohydrate antigen 199 (CA199)], and survival rates were compared between the two groups. Results The total effective rate of the combined group was significantly higher than that of the control group (P<0.05). No significant difference was observed in disease control rates between the two groups (P> 0.05). At the end of the treatment, the expression levels of serum EC, VEGF, MMP-9, AFP, ALT, TBIL, CA199, and GGT decreased in both groups, with the combined group showing significantly lower levels than the control group (P<0.05). There was no significant difference in the 6-month and 1-year survival rates be- tween the two groups (P>0.05), but the 2-year survival rate was higher in the combined group, with a statistically significant difference (P<0.05). Conclusion The combination of TACE and RFA in treating primary hepatocellular carcinoma is beneficial in improving short-term therapeutic effects, reducing serum tumor markers, and enhancing safety, and can increase the 2-year survival rate of patients. [ABSTRACT FROM AUTHOR]

Background: Few studies have explored the expression profile of RPL3 in breast cancer (BRCA). Our research provided an in-depth analysis of RPL3 expression patterns in BRCA, highlighting its significance for therapy prediction and prognosis. Methods: RPL3 was notably elevated in malignant cells, and its expression level was closely associated with tumor size and overall survival outcomes. Our study also identified RPL3-related terms and pathways and revealed a strong correlation between RPL3 expression and breast carcinoma immunity, demonstrating inconsistent expression levels in various immune cell lines. In addition, we examined the relationship between RPL3 expression and tumor mutational burden (TMB) in BRCA. To assess the clinical implications of BRCA chemotherapy, we investigated the correlation between RPL3 expression levels and drug sensitivity. Results: Our findings suggest that RPL3 plays a critical role in the BRCA process and is associated with immune infiltration, indicating its potential as a novel immunotherapy target in BRCA treatment. Conclusions: In summary, our research underscores the importance of RPL3 expression levels in tumorigenesis and its potential for guiding BRCA immunotherapy. [ABSTRACT FROM AUTHOR]

Objective: Testicular tumor (TT) is a uncommon disease posing serious health problem. There are differences in some aspects between adult and pediatric TT. The study was to compare their differences of clinical and histological characteristics through the analysis of the long-term experiences in TT patients from two institutions. Materials and methods: The clinical data of hospitalized patients was collected and analyzed retrospectively from January 2014 to January 2024 at a pediatric and an adult institution, respectively. The data included composition, gender, age, initial presentation, tumor size, tumor markers, pathological diagnosis. Results: A total of 195 hospitalized patients were included. There were 135 children and 60 adult with TT, respectively. Of these children, patients were aged from 1 month to 14 years, with a mean age of 2.32 years. More cases (37.04%) were diagnosed at age younger than 1 years. 69 cases were left-sided, 65 cases were right-side and only 1 case was bilateral. Pediatric TTs mainly included 82 prepubertal teratomas, 37 had prepubertal yolk sac tumors and 3 mixed malignant germ tumors. Testicular surgeries included testicular-sparing surgery (TSS) (n = 73), radical orchiectomy (n = 60), and testicular biopsy (n = 2). There were 24 patients receiving postoperative chemotherapy. Adult TTs mainly contained 17 seminomas, 10 prepubertal teratomas,7 postpubertal teratomas, 6 stromal tumors and 3 embryonal carcinomas. The average age was 34.08 years. There were 29 right-sided, 27 left-sided and 4 bilateral tumors. TSS (n = 26), radical orchiectomy (n = 33), and testicular biopsy (n = 1) were performed in these TT patients. Only 6 patients received postoperative chemotherapy. The most common symptom was a painless scrotal mass at initial diagnosis in both groups. In addition, we found that significant differences were explored between histological type and age, tumor size (P < 0.05). Yolk sac tumor and seminoma were the most common malignant TT in pediatric and adult population, respectively. After two year follow-up, two children with yolk sac tumor and 4 adults with seminoma died of their diseases. Conclusions: The majority of pediatric cases were benign compared to adult. The most common type was prepubertal teratoma and yolk sac tumor. Pediatric TTs often occurred under the age of 1 year. Seminomas and prepubertal teratomas were commonly found in adult TTs, especially for young adult. We found that pediatric tumor type was associated with age and tumor size. TSS should be considered for benign TTs based on frozen biopsy findings in children. [ABSTRACT FROM AUTHOR]

Tumor‐derived extracellular vesicles (EVs) are potential biomarkers for tumors, but their reliable molecular targets have not been identified. The previous study confirms that ubiquitin‐specific protease 22 (USP22) promotes lung adenocarcinoma (LUAD) metastasis in vivo and in vitro. Moreover, USP22 regulates endocytosis of tumor cells and localizes to late endosomes. However, the role of USP22 in the secretion of tumor cell‐derived EVs remains unknown. In this study, it demonstrates that USP22 increases the secretion of tumor cell‐derived EVs and accelerates their migration and invasion, invadopodia formation, and angiogenesis via EV transfer. USP22 enhances EV secretion by upregulating myosin IB (MYO1B). This study further discovers that USP22 activated the SRC signaling pathway by upregulating the molecule KDEL endoplasmic reticulum protein retention receptor 1 (KDELR1), thereby contributing to LUAD cell progression. The study provides novel insights into the role of USP22 in EV secretion and cell motility regulation in LUAD. [ABSTRACT FROM AUTHOR]

Objective Patients and Methods Results Conclusions To assess recurrence‐free survival (RFS) in patients with undetectable tumour‐informed circulating tumour DNA (ctDNA) before radical cystectomy (RC) and evaluate if those who converted from detectable to undetectable ctDNA status after RC have similar RFS outcomes as those with persistently undetectable ctDNA status.Patients who underwent RC had prospectively and longitudinally collected tumour‐informed ctDNA analyses during 2021–2023. ctDNA status was informed from the pre‐RC specimen. The minimal residual disease (MRD) window was defined as the initial 90 days after RC. RFS was evaluated using the Kaplan–Meier method. Cox regression analysis was performed to find predictors of disease recurrence.The cohort included 135 patients with 647 ctDNA analyses. The median (interquartile range [IQR]) age was 71 (63–77) years. Over a median (IQR) follow‐up of 11 (7–18) months, 41 patients (30%) had a recurrence. Pre‐RC undetectable ctDNA status was found in 54 patients (40%). The RFS rates at 6, 12, and 21 months were 98%, 93%, and 82%, respectively. Of 77 patients with undetectable ctDNA status at the MRD window available for conversion dynamics analysis, 43 had persistently undetectable ctDNA status (both at pre‐RC and MRD window) and 31 converted from pre‐RC detectable to MRD undetectable status (conversion group). The persistently undetectable group had significantly better RFS than the conversion group (log‐rank, P < 0.001), with 12‐month RFS rates of 97% vs 51%, and 18‐month RFS rates of 88% vs 51%, respectively. On Cox multivariate analysis, only the conversion group status predicted disease recurrence.Patients with undetectable pre‐RC ctDNA status have a favourable prognosis and may be candidates for treatment de‐escalation. Those with persistently undetectable ctDNA had superior RFS compared to the conversion group. Pre‐RC ctDNA status should be incorporated into trials examining ctDNA use in clinical decision‐making. [ABSTRACT FROM AUTHOR]

(1) Background: The Mixed lineage leukemia 1 (MLL1) gene, located on chromosome 11q23, plays a pivotal role in histone lysine-specific methylation and is consistently associated with various types of leukemia. Non-synonymous Single Nucleotide Polymorphisms (nsSNPs) have been tied to numerous diseases, including cancers, and have become valuable cancer biomarkers. There's a notable gap in studies probing the influence of SNPs on MLL1 protein structure, function, and subsequent modifications; (2) Methods: We utilized an array of bioinformatics tools, including PredictSNP, InterPro, ConSurf, I-Mutant2.0, MUpro, Musitedeep, Project HOPE, RegulomeDB, Mutpred2, and both CScape and CScape Somatic, to meticulously analyze the consequences of nsSNPs in the MLL1 gene; (3) Results: Out of 2,097 nsSNPs analyzed, 62 were determined to be significantly pathogenic by the PredictSNP tool, with ten crucial MLL1 functional domains identified using InterPro. Additionally, 50 of these nsSNPs had high conservation scores, hinting at potential effects on protein structure and function, while 32 were found to undermine MLL1 protein stability. Notably, four nsSNPs were deemed oncogenic, with two identified as cancer drivers. The nsSNP, D2724G, between the MLL1 protein's FY-rich domains, could disrupt proteolytic cleavage, altering gene expression patterns and potentially promoting cancer; (4) Conclusions: Our research provides a comprehensive assessment of nsSNPs' impact in the MLL1 protein structure and function and consequently on leukemia development, suggesting potential avenues for personalized treatment, early detection, improved prognosis, and a deeper understanding of hematological malignancy genesis. [ABSTRACT FROM AUTHOR]

Exosomes are critical tumor biomarkers, which can be detected by label‐free sensing of plasmonic metasurfaces with expensive antibody functionalization. Due to their low cost and small size, aptamers should be promising to replace antibodies in plasmonic metasensing of exosomes. However, research on aptamer‐based plasmonic metasensing of exosomes is still unexplored. Here, the optical near‐field sensing mechanism of aptamer‐based plasmonic metasurface (APM) is investigated. Based on the study of the evanescent field of APM, using thiol‐modified aptamer boosts the utilization rate of resonance wavelength shift from 27.5% to 83.3% compared to biotinylated aptamers, attributed to a significant reduction in the near‐field occupation of the biofunction layer. Moreover, APM biosensors effectively detect clinical serum exosomes for breast cancer (BC) diagnosis and classification. The receiver operating characteristic analysis shows an area under the curve of 99.3% for APM diagnosis, surpassing the 79.1% for hematological tests of the conventional BC biomarker CA153. The results also indicate that APM biosensors can be a noninvasive tool for molecular classification of BC with great distinguishment of P < 0.0001. The research demonstrates that APM biosensors are enabling a reliable and convenient platform to facilitate clinical hematological tests of exosomes for auxiliary diagnosis of cancer. [ABSTRACT FROM AUTHOR]

Glycoproteins are a class of key biomacromolecules in the human body, which participate in a wide range of biological processes. Glycoproteins have emerged as important biomarkers in clinical diagnosis. Notably, some common tumor markers under clinical screening include glycoproteins such as alpha-fetoprotein (AFP). The elevated AFP concentration in serum has been widely regarded as an indicator of hepatocellular carcinoma. The human AFP contains one N-glycan, which consists of GlcNAc, mannose, sialic acid and galactose. Wheat-germ agglutinin (WGA), one of the representative lectins, can bind GlcNAc and has been chosen as a capable bio-recognition element in fabricating a potentiometric biosensor for AFP determination. The fabricated potentiometric biosensor relies on the surface blocking of the polymeric membrane ion-selective electrode by the AFP glycoprotein, which leads to a change in the ion flux of the tetrabutylammonium chloride marker ion under zero-current conditions. The WGA-based potentiometric biosensor was successfully exploited in quantifying AFP within the range of 0.01 to 100 ng mL−1, yielding a limit of detection as low as 5 pg mL−1. Outstanding specificity, reproducibility and repeatability were observed for the fabricated potentiometric biosensor. Furthermore, the potentiometric biosensor was subjected to measurements within real mouse serum samples via spiking by varying the AFP amounts. Excellent recoveries were obtained, which indicated the potentiometric biosensor's capability to determine glycoproteins within complex matrices. Note that the proposed biosensor provides a feasible and specific method of quantifying glycoprotein biomacromolecules under the potentiometric mode, which effectively expands the potentiometric toolbox to enable the detection of a wide variety of analytes, not being limited to common ions. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion Colorectal cancer is the third most common cancer worldwide. Micropapillary carcinoma (MPC) is increasingly identified as a poor prognostic marker in various cancers, including breast, bladder and lung. It remains an under recognized subtype in colorectal cancer. The aim of this study is to evaluate the prevalence, implications and impact on survival of MPC in colorectal cancer in an Australian cohort.A retrospective review of all colorectal cancer resections in two tertiary centres in Sydney Australia was performed, between 2019 and 2024. MPC was identified on histolopathology as per standard guidelines of the resected specimens. Variables collected included age, sex, TNM, site, lymphovascular invasion (LVI), and lymph node involvement.Of 597 colorectal cancer resections during the study period, 21 cases of MPC were identified (3.5%). Mean age was 60 years (SD 15 years). Twenty patients (95%) had T3–T4 tumours, 19 (90%) had positive lymph node involvement, 18 (86%) had confirmed or suspected LVI, and 4 (19%) had distant metastatic disease. Overall 1‐year survival was 90% and 3‐year survival was 76%.MPC is associated with high risk features in colorectal adenocarcinoma. Accurate histopathological diagnosis of these more aggressive cancers should guide prognostication, individualized adjuvant treatment and close surveillance. [ABSTRACT FROM AUTHOR]

Background: Today, breast cancer is the most diagnosed cancer worldwide. There are many different clinical presentations, radiological characteristics, and histological types of breast cancer. HER2 is overexpressed in a significant number of breast cancer cases reaching 20% of all breast cancers, and its overexpression is seen directly proportionate with a poor outcome and prognosis. Methods: We started this cross-sectional research from January 2022–December 2023 on 202 breast cancer patients who had 220 lesions. The molecular subtypes of the different lesions were determined in all the included cases. Magnetic resonance imaging (MRI) studies were conducted in all included cases. The MRI parameters included conventional MRI, diffusion-weighted analysis, and dynamic post-contrast T1-weighted imaging. Results: The prevalence of irregular margins (P < 0.001), linear and segmental distribution (P = 0.044), heterogeneous pattern (P < 0.001), and type 2 curve was statistically significantly higher in the HER2-positive lesions. Nipple infiltration incidence showed statistically significant elevation in the HER2-positive lesions (P = 0.017). The lesions' ADC and perilesional ADC in the HER2-positive lesions were also statistically significantly elevated. The best cutoff point of ADC to detect lesions with positive HER2 expression was > 0.885 × 10–3 mm2/s, with 65.7% sensitivity and 60% specificity, with a statistically significant value (p = 0.005). Conclusions: Magnetic resonance imaging of breast imaging is a promising noninvasive method for identifying breast tumors with the HER2 molecular subtype. Combining various radiological features by MRI may provide a conclusion for recognizing positive HER2 lesions. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) is a disease highly associated with epigenetic modification, and arginine methylation is particularly important in its genetic regulation. However, the role of arginine methylation related lncRNAs in breast cancer has not been studied. First, we identified the related lncRNAs (from TCGA database) according to the differentially expressed genes related to arginine methylation in breast cancer. Then the lncRNAs related to protein arginine methylation were obtained by regression analysis, and the risk score model was constructed. Finally, the cell experiment and subcutaneous tumor model verified that the arginine methylation related lncRNA z68871.1 in the model had a significant effect on the proliferation and invasion of breast cancer cells. In conclusion, we successfully constructed an arginine methylation related lncRNA model, which has strong predictive ability. At the same time, this study provides an experimental basis for exploring the mechanism of arginine methylation in BC and helps to find new biomarkers of BC. [ABSTRACT FROM AUTHOR]

Introduction: The apparent diffusion coefficient (ADC) is a quantitative parameter that facilitates the detection and reliable differentiation of rectal cancer. MR differentiation between rectal carcinoma, post-radiation proctitis, and normal rectal wall with the ADC values and their comparison depending on the level of tumor markers and pathohistological characteristics of rectal carcinoma. Methods: The retrospective study performed at the Oncology Institute of Vojvodina included 300 patients, 100 each with rectal cancer, post-radiation proctitis, and normal rectum. Mean ADC values were obtained by measuring the region of interest (ROI) of the rectal wall. Results: Rectal cancer showed lower ADC values (0.665 ± 0.086 x 10-3mm2/s) compared to both post-radiation proctitis (1.648 ± 0.268 x 10-3mm2/s) and normal rectum (1.180 ± 0.110 x 10-3mm2/s) (p<0.001). No significant differences in ADC values were observed between different grades of rectal cancer (p=0.874; p>0.05), depending on the presence of metastases in the lymph nodes (p=0.357; p>0.05), different TN stage (p=0.196; p>0.05), local spread of the tumor (p=0.312; p>0.05), the presence of RAS mutation (p=0.829; p>0.05) and the value of tumor markers (p=0.923; p>0.05). ADC values below 1.013 x 10-3mm2/s with 100% sensitivity and 96% specificity indicate the presence of rectal cancer in relation to normal wall, with a positive predictive value of 96.1% and a negative of 100%. ADC values below 1.255 x 10-3mm2/s with 100% sensitivity and 95% specificity indicate rectal cancer in relation to post-radiation proctitis. ADC values above 1.339 x 10-3mm2/s with 87% sensitivity and 89% specificity indicate post-radiation proctitis in relation to normal wall. Discussion: The ADC is a useful marker in differentiating between rectal cancer, post-radiation proctitis, and normal rectal wall with high sensitivity and specificity, but it cannot be used to distinguish the histological grades of rectal cancer, nor other pathohistological parameters. [ABSTRACT FROM AUTHOR]

Cancer, the world’s second leading cause of death after cardiovascular diseases, is characterized by hallmarks such as uncontrolled cell growth, metastasis, angiogenesis, hypoxia, and resistance to therapy. Autophagy, a cellular process that can both support and inhibit cancer progression, plays a critical role in cancer development and progression. This process involves the formation of autophagosomes that ultimately fuse with lysosomes to degrade cellular components. A key regulator of this process is Sirtuin 1 (SIRT1), which significantly influences autophagy. This review delves into the role of SIRT1 in modulating autophagy and its broader impacts on carcinogenesis. SIRT1 regulates crucial autophagy mediators, such as AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR), effectively promoting or suppressing autophagy. Beyond its direct effects on autophagy, SIRT1’s regulatory actions extend to other cell death processes, including apoptosis and ferroptosis, thereby influencing tumor cell proliferation, metastasis, and chemotherapy responses. These insights underscore the complex interplay between SIRT1 and autophagy, with significant implications for cancer therapy. Targeting SIRT1 and its associated pathways presents a promising strategy to manipulate autophagy in cancer treatment. This review underscores the potential of SIRT1 as a therapeutic target, opening new avenues for enhancing cancer treatment efficacy. [ABSTRACT FROM AUTHOR]

The connections between cancer stem cells (CSCs) and epithelial-mesenchymal transition (EMT) is critical in cancer initiation, progression, metastasis, and therapy resistance, making it a focal point in cancer theragnosis. This review provides a panorama of associations and regulation pathways between CSCs and EMT, highlighting their significance in cancer. The molecular mechanisms underlined EMT are thoroughly explored, including the involvement of key transcription factors and signaling pathways. In addition, the roles of CSCs and EMT in tumor biology and therapy resistance, is further examined in this review. The clinical implications of CSCs-EMT interplay are explored, including identifying mesenchymal-state CSC subpopulations using advanced research methods and developing targeted therapies such as inhibitors and combination treatments. Overall, understanding the reciprocal relationship between EMT and CSCs holds excellent potential for informing the development of personalized therapies and ultimately improving patient outcomes. [ABSTRACT FROM AUTHOR]

Accurate prostate cancer (PCa) patient diagnosis and risk assessment are key to ensure the best outcome. Currently, low- and favorable intermediate-risk PCa patients may be offered AS due to the indolent nature of the disease. Nonetheless, deciding between active surveillance and curative-intent treatment remains an intricate task, as a subset of these patients may eventually progress, enduring poorer prognosis. Herein, we sought to construct risk calculators based on cancer biomarkers, enabling more accurate discrimination among patients which may benefit from active interventions. Ki67 immunoscore, GSTP1 and KLF8 promoter methylation levels (me) were assessed in PCa tissues. Study endpoints included overall and biochemical recurrence-free (BCR) survival. Combination with relevant clinicopathological parameters allowed for construction of graphical calculating tools (nomograms). Higher Ki67 index correlated with worse BCR-free survival, whereas higher KLF8me levels were associated with improved overall survival, especially in patients with lower-grade tumors. GSTP1me levels had no prognostic value. Among prognostic models tested, a BCR-risk calculator – ProstARK (including Ki67 and clinicopathologic parameters) – disclosed 79.17% specificity, 66.67% sensitivity, 55% positive predictive value, 86% negative predictive value, and 75.76% accuracy. Similar results were found using an independent PCa biopsy cohort, validating its prognostication ability. Combining clinicopathologic features and Ki67 index into a risk calculator enables easy and accurate implementation of a novel PCa prognostication tool. This nomogram may be useful for a more accurate selection of patients for active surveillance protocols. Nonetheless, validation in a larger, multicentric, set of diagnostic PCa biopsies is mandatory for further confirmation of these results. [ABSTRACT FROM AUTHOR]

Chronic liver disease is closely linked to dietary intake factors, such as high consumption of simple carbohydrates including sucrose. In this study, the influence of sucrose on the development of hepatocellular carcinoma (HCC), the most common primary liver malignancy, was explored. Using the hepatocarcinogen diethylnitrosamine (DEN) to induce HCC in the rat, we co-administered sucrose with DEN. The co-administration significantly modified body, liver and pancreas weight, as well as, serum fatty acids and triglycerides. DEN caused liver structural alteration, fibrosis, and tumor formation; surprisingly, co-administration with sucrose restored hepatic lipids, improved liver architecture, and reduced fibrosis and tumor development. Sucrose intake negatively regulated tumor markers and cell proliferation, and reduced the expression of genes associated with lipid metabolism and oxidative stress response. These findings highlight a hepatoprotective effect of sucrose during DEN-induced hepatocarcinogenesis, underlining an intriguing role of high sucrose consumption during HCC development and providing new insights as well as possible pathways of cellular protection under sucrose intake on hepatocarcinogenesis. [ABSTRACT FROM AUTHOR]

ABSTRACT Only a limited number of tumour biomarkers are currently available in veterinary medicine, particularly in cats. Cell‐free DNA (cfDNA) is an extracellular DNA fragment released upon cell death and is considered a minimally invasive biomarker for the diagnosis and monitoring of various human malignancies. This study aimed to clarify the utility of circulating cfDNA as a liquid biopsy for various feline tumours. Plasma samples were collected from 44 cats with various tumours, 24 cats with other diseases and 10 healthy controls. A follow‐up study was conducted in three tumour‐bearing patients. All cfDNA concentrations were quantified via real‐time polymerase chain reaction (PCR), which provided short and long fragments of a newly identified feline LINE‐1 gene. We found that cfDNA levels were significantly higher in cats with various tumours than in those with other diseases or healthy controls. The cfDNA concentration was not correlated with serum amyloid A (SAA) levels. Cats with tumours exhibited elevated cfDNA levels that predicted tumour‐bearing with a sensitivity and specificity of 50.5% and 91.2%, respectively (AUC 0.736; p < 0.001). In lymphoma cases, cats with high cfDNA levels had significantly shorter survival times than those with low cfDNA levels (median: 33 days vs. 178 days; p = 0.003). In addition, the cfDNA levels of the three patients correlated with clinical status during follow‐up. Collectively, these findings indicate the potential of cfDNA as a useful biomarker for the diagnosis, therapeutic monitoring and prognostic assessment of tumours in cats. [ABSTRACT FROM AUTHOR]

Background: Gastric cancer stands as one of the most prevalent malignancies globally, conventional endoscopic specimens have been the primary means of diagnosing preoperative gastric histopathology, however, their limitations in capturing intra-tumor heterogeneity compromise their efficacy in evaluating angiogenesis. Perfusion Computed Tomography (P-CT) emerges as a pivotal functional imaging modality, facilitating objective assessment of tissue perfusion, serving as a marker of angiogenesis. So, our research objective was to evaluate the efficacy of CT perfusion imaging in the prediction of histological grades of gastric tumors using quantitative perfusion parameters such as permeability surface (PS), blood flow (BF), mean transient time (MTT), and blood volume (BV), in addition to the qualitative scoring system then comparing the findings with the histopathological results. Results: PS and BF were statistically significant predictors of the grade of differentiation, their odds ratio (OR) was (1.05, 95% CI 1.02–1.09, for each of them) (P = 0.004, P = 0.009, respectively). MTT also emerged as a significant predictor of the grade of differentiation with an OR of 0.76 (95% CI 0.57–0.93, P = 0.025). Using multivariate logistic regression model, PS was the most potent individual P-CT predictor of differentiation of the grade and the diagnosis of poorly differentiated tumors at ≥ 39 mL/100 g/min cut off point, followed by BF at ≥ 82.2 mL/100 g/min, and MTT at < 8.4 s. Regarding the qualitative scoring system P-CT, poorly differentiated tumors generally received higher scores of PS (P < 0.001), BF (P < 0.001), and BV (P = 0.017), than well and moderately differentiated tumors, however, MTT showed that poorly differentiated tumors were more frequently scored as low compared to well and moderately differentiated tumors (P < 0.001). Conclusions: P-CT is an innovative, non-invasive biomarker for predicting gastric cancer grade by quantitative and qualitative assessment by P-CT parameters (PS, BF and MTT) with particular role of PS as the strongest individual P-CT predictor of differentiation grade followed by BF and MTT at specific cut off points. [ABSTRACT FROM AUTHOR]

Background: Enhancing the prognosis and treatment outcomes of oral cancer relies heavily on its early detection. This study aims to establish a connection between serum and salivary dipeptidyl peptidase-4 (DPP-4) levels and oral squamous cell carcinoma (OSCC), comparing them with oral potentially malignant lesions (OPMLs) and control subjects and validating salivary DPP-4 as a diagnostic marker for the early detection of oral cancer. Methodology: Forty-five systemically healthy individuals were categorized into three groups: Group I consisted of 15 patients diagnosed with OSCC, Group II comprised 15 patients with OPMLs (including leukoplakia and oral lichen planus), and Group III included 15 participants without any oral mucosal lesions. Serum and whole unstimulated salivary samples were collected from all participants to assess DPP-4 levels using an enzyme-linked immunosorbent assay (ELISA) kit. Receiver operating characteristic (ROC) analysis was conducted to determine the area under the curve (AUC), sensitivity, specificity, and diagnostic accuracy of DPP-4. Results: Both serum and salivary DPP-4 levels were highest in the healthy group, followed by OPMLs, and lowest in the OSCC group, with statistically significant differences observed. ROC analysis demonstrated excellent diagnostic accuracy of salivary DPP-4 in distinguishing OSCC from healthy individuals, OPMLs from healthy individuals, and OSCC from OPMLs, with accuracies of 100%, 100%, and 96.67%, respectively. Salivary DPP-4 levels also exhibited a statistically significant correlation with OSCC grades. Conclusions: DPP-4 appears to play a protective, anti-oncogenic role in maintaining oral tissue health. The remarkable diagnostic accuracy of both serum and salivary DPP-4 in discriminating between OSCC, OPMLs, and healthy controls suggests its potential utility as a well-established marker for early oral cancer diagnosis. Salivary DPP-4, being non-invasive, could serve as a convenient chair-side diagnostic tool for the early detection of OSCC. Clinical trial registration: The study was retrospectively registered on clinicaltrial.gov with NCT06087042, date of registration (first posted date): 17/10/2023 [ABSTRACT FROM AUTHOR]

Background: As the emergence of technologies such as sequencing and gene mapping, significant advancements have been made in understanding the landscape of tumors. However, the effective treatment of tumors continues to pose a tremendous challenge in clinical practice, which highlights the importance of predicting tumor markers and studying drug resistance mechanisms. The prognosis and differential expression of STARD7 in human pan-cancer were investigated by bioinformatic methods and experimental verification. Methods: The expression, diagnostic, and prognostic significance of the STARD7 gene were comprehensive analyzed using bioinformatics techniques. Furthermore, we validated our projected outcomes in liver cancer through experimental methodologies, including the use of qRT-PCR, CCK8 and transwell assays. Results: The STARD7 gene exhibits differential expression in 25 tumors, with high expression observed in 22 tumors. These distinct expression patterns within different tumor types are closely associated with poor prognosis and diagnosis. Furthermore, the STARD7 gene plays a role in regulating the tumor immune microenvironment. Methylation levels of STARD7 vary among 20 types of tumors and are correlated with survival outcomes. Furthermore, the experiment results demonstrated that STARD7 is highly expressed in hepatocellular carcinoma cells. Suppression of STARD7 significantly impedes the proliferation, migration, and invasion of HepG-2 and SMMC-7721 cells. Conclusions: STARD7 has the potential to function as a crucial prognostic biomarker and exhibit correlation with tumor immunity in various types of human cancers. The implications of our findings extend to informing cancer immune-therapy and promoting the advancement of precision immune-oncology. [ABSTRACT FROM AUTHOR]

Introduction: Almost all cases of malignant acanthosis nigricans with oral manifestations occurred in older age groups. Here, we report a case of malignant acanthosis nigricans in a young female presented with chief complaints of oral mucosal hyperplasia, who had previously been diagnosed with allergies. Case presentation: A 30-year-old female developed oral hyperplasia and rash following seafood consumption, with subsequent resolution of the rash but persistent oral lesions and the appearance of pigmentation on her hands, neck, and axillae. Clinical examination revealed papillomatosis, hyperemia, and velvety hyperplasia in the oral cavity. Biopsy results confirmed papillary hyperplasia. Despite the patient’s belief in good health, she was advised to undergo further systemic examinations. Elevated serum tumor markers and histologic analysis of an endoscopic biopsy confirmed gastric cancer with duodenal infiltration, leading to the diagnosis of malignant acanthosis nigricans. Unfortunately, the patient passed away due to heart failure during chemotherapy treatment. Conclusions: The majority of patients with malignant acanthosis nigricans present with oral lesions before the underlying malignancy is detected, emphasizing the importance of timely comprehensive systemic examination. Furthermore, our case suggests that age may not be a restrictive factor for the development of malignant acanthosis nigricans, and the presence of a rash can potentially obscure the cutaneous manifestations associated with this condition. [ABSTRACT FROM AUTHOR]

Background: The most prevalent subtype of non-Hodgkin lymphoma is diffuse large B-cell lymphoma (DLBCL). Germinal center B-cell (GCB) and non-germinal center B-cell (non GCB) are the two main biologically different molecular subtypes identified utilizing an immunohistochemistry-based approach. Aim: Our objective in this study is to analyze the impact of immunohistochemical subtypes of DLBCL (GCB or non GCB) on demographic and clinicopathological parameters, response to chemotherapy and survival outcomes. Subjects and methods: This is a retrospective study including 106 cases of DLBCL collected in the department of pathology, Hassan II university hospital, Fez (Morocco), over a period of 12 years (January 2010-September 2022). The subtypes of DLBCLs were defined according to Hans algorithm, using immunohistochemistry by three biomarkers (CD10, BCL6, MUM1). Statistical analysis used: Independent t tests and analyses of variance were used for the comparison of mean values. We employed the SPSS 26.0 program to achieve this. A statistically significant value was set at P <.05. Results: Seventy-five patients (71%) were non-GCB subtype, while thirty-one patients (29%) had the GCB immunosubtype. We have found a significant (P <.05) correlations between DLBCL immunosubtypes and treatment responses on one hand and survival in the other hand. In the GCB subtype, the response rate and survival were significantly improved. A significant association was found between Ki 67 expression and survival on univariate analysis. On multivariate analysis, we note a correlation between Ki 67 expression, DLBCL immunohistochemical subtypes and survival outcome. Conclusion: Non GCB subtype is associated with poor response to treatment and inferior survival outcome compared to GCB subtype in Moroccan context, especially when combined with high expression of Ki 67 marker. [ABSTRACT FROM AUTHOR]

Solid tumours are complex and heterogeneous systems, which exist in a dynamic biophysical microenvironment. Conventional cancer research methods have long relied on two-dimensional (2D) static cultures which neglect the dynamic, three-dimensional (3D) nature of the biophysical tumour microenvironment (TME), especially the role and impact of interstitial fluid flow (IFF). To address this, we undertook a transcriptome-wide analysis of the impact of IFF-like perfusion flow using a spheroid-on-chip microfluidic platform, which allows 3D cancer spheroids to be integrated into extracellular matrices (ECM)-like hydrogels and exposed to continuous perfusion, to mimic IFF in the TME. Importantly, we have performed these studies both in experimental (normoxia) and pathophysiological (hypoxia) oxygen conditions. Our data indicated that gene expression was altered by flow when compared to static conditions, and for the first time showed that these gene expression patterns differed in different oxygen tensions, reflecting a differential role of spheroid perfusion in IFF-like flow in tumour-relevant hypoxic conditions in the biophysical TME. We were also able to identify factors primarily linked with IFF-like conditions which are linked with prognostic value in cancer patients and therefore could correspond to a potential novel biomarker of IFF in cancer. This study therefore highlights the need to consider relevant oxygen conditions when studying the impact of flow in cancer biology, as well as demonstrating the potential of microfluidic models of flow to identify IFF-relevant tumour biomarkers. [ABSTRACT FROM AUTHOR]

While it is recognized that early diagnosis of cancer-related biomarkers can become an effective avenue for timely treatment and successfully improve patient survival, it remains challenging to get accurate inspection results. Currently, most reported cancer biomarker sensing methods are focused on the quantitative detection of a single type of biomarker, which makes accurate medical diagnostics difficult. In this work, we constructed a DNA walker nanomachine aptasensor based on gold nanoparticles for the simultaneous sensing of dual cancer biomarkers. The aptamers, labelled with a fluorophore, hybridized with complementary strands on the gold nanoparticle surface, serve as a walking track. Target analytes bind to their specific aptamers, leading to the dissociation of the unstable double-strand spherical nucleic acid. Exonuclease I (Exo I) selectively digested the aptamers bound with the target analytes, then the released targets go back to the next apamers on the gold nanopareticles surface for walking. The use of spherical nucleic acid probes improved the sensitivity of analyte detection. Exo I provided a driving power for target recycling and considerably improved the sensitivity of the aptasensor as well. The DNA walker nanomachine aptasensor was successfully applied for the detection of carcinoembryonic antigen (CEA) in the range of 0.167 to 3.34 ng mL−1, and mucin-1 (MUC-1) in the same range. Moreover, we used the two aptamers to construct the DNA walker nanomachine and achieved the simultaneous detection of CEA and MUC-1, thus having great potential for biomolecular logic gate construction and early disease diagnosis. [ABSTRACT FROM AUTHOR]

AbstractBackgroundMethodsResultsConclusionColorectal cancer (CRC) ranks among the most aggressive types of cancer globally. Currently, clinical tumor prognostic biomarkers still lack accuracy. Mitotic spindle positioning (MISP) protein connects microtubules to the actin cytoskeleton and adhesive plaques, playing a critical role in spindle positioning, orientation, and the process of cell division. MISP can regulate the malignant biological functions of pancreatic cancer and intrahepatic cholangiocarcinoma and it acts as biomarker for prognosis, but its role in CRC remains unclear.This study has collected 37 CRC tissue samples and 37 corresponding adjacent nontumor tissue samples, and 57 additional CRC tissues samples. Clinical data were obtained from the patients with CRC. MISP mRNA and protein expression levels were analyzed in normal control and CRC tissues using the GEPIA and Human Protein Atlas website. MISP protein levels in the collected tissues were analyzed using immunohistochemistry.MISP mRNA and protein expression levels were significantly increased in CRC tissues compared to adjacent nontumor tissues. Higher MISP protein levels were associated with distant metastasis, recurrence, and lower survival rates. Kaplan–Meier analysis showed that high expression levels of MISP protein were associated with recurrence and death in CRC patients. In addition, a high expression level of MISP protein, lymph node metastasis, and distance metastasis were risk factors for recurrence and a poor prognosis in patients with CRC.Elevated MISP protein correlated with tumor metastasis, recurrence, and lower survival rates in patients with CRC, and thus, MISP has the potential to become a prognostic marker for CRC. [ABSTRACT FROM AUTHOR]

Objective: To explore the efficacy of argon-helium cryoablation (AHC) combined with chemotherapy in the treatment of advanced non-small cell lung cancer (NSCLC). Methods: A retrospective study was carried out between February 2020 to June 2022 of 85 patients with advanced NSCLC admitted to Tianjin Cancer Hospital Airport Hospital. Patients were categorized into two groups based on whether they had received AHC: patients received chemotherapy treatment alone (chemotherapy group, n=41); patients received chemotherapy combined with AHC (combined group, n=44). Tumor control rate, serum tumor marker levels, quality of life, and median survival time between the two groups were compared. Results: Tumor control rate in the combined group (86.36%) was significantly higher than that in the chemotherapy group (68.29%) (P<0.05). After treatment, the levels of serum cytokeratin 19 fragment (CYFRA21-1), carcinoembryonic antigen (CEA) and glycoprotein antigen 125 (CA125) in the two groups were significantly lower than those before the treatment, and significantly lower in the combined group compared to the chemotherapy group (P<0.05). After the treatment, the quality of life of patients in both groups was significantly higher than before the treatment. Quality of life in the combined group was significantly higher than in the chemotherapy group (P<0.05). One year after treatment, the median survival time of the combined group (10.5 months; 95% CI: 9.775-11.225) was significantly higher than that of the chemotherapy group (9.4 months; 95% CI: 8.55-10.323) (P=0.045). Conclusions: Compared with chemotherapy alone, conventional chemotherapy combined with AHC in the treatment of advanced NSCLC can significantly reduce the levels of serum tumor markers and improve overall treatment efficacy, quality of life and 1-year overall survival rate. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the clinical effects of intraperitoneal chemohyperthermia (IPCH) in the treatment of postoperative patients with advanced stage ovarian cancer, and its impacts on tumor markers and immune functions. Methods: This is a retrospective study. One hundred and twenty patients with advanced stage ovarian cancer received in Shanghai 7th People’s Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from May 10, 2022 to June 10, 2023 were selected and randomly divided into control and study groups (n=60 each group). Patients in the control group were administered routine intravenous chemotherapy, the study group underwent IPCH besides routine intravenous chemotherapy based on the control group. Comparatively analyzed the clinical effects, adverse reaction occurrence rates, and variations in relevant observation targets, the tumor marker after and before the treatment. Results: Total efficacy in the study and control groups are proved to be with statistically significant differences. The occurrence of adverse reactions proved that no significant differences is seen between both groups. After the treatment, CEA, CA19-9, and CA125 levels in patients of the study group are apparently lower than those in the control group, showing statistically significant differences; expression levels of CD3+, CD4+ and CD4+/CD8+, in the study group were enormously above those in the control group after the treatment, with statistically significant differences. Conclusions: IPCH has the potential to effectively enhance comprehensively clinical therapeutic effects among postoperative patients with ovarian cancer, significantly improve patients’ immune states, and evidently reduce expression levels of various tumor markers. [ABSTRACT FROM AUTHOR]

Background: Melanoma is the most aggressive skin cancer with ability to recur also after early‐stage tumor surgery. The aim was to identify early‐stage melanoma patients at high risk of recurrence using liquid biopsy, estimating of mutated BRAF ctDNA and the level of tumor marker S100B in plasma. Methods: Eighty patients were enrolled in the study. BRAF V600E mutation was determined in FFPE tissue and plasma samples using ultrasensitive ddPCR with pre‐amplification. The level of S100B was determined in plasma by immunoassay chemiluminescent method. Results: The best prediction of melanoma recurrence after surgery was observed in patients with combined high level of S100B (S100Bhigh) and ctDNA BRAFV600E (BRAFmut) in preoperative (57.1% vs. 12.5%, p = 0.025) as well as postoperative blood samples (83.3% vs. 14.3%, resp., p = 0.001) in comparison with low S100B and BRAF wild‐type. Similarly, patients with preoperative and postoperative S100Bhigh and BRAFmut experienced worse prognosis (DFI p = 0.05, OS p = 0.131 and DFI p = 0.001, OS = 0.001, resp.). Conclusion: We observed the benefit of the estimation of combination of S100B and ctDNA BRAFmut in peripheral blood for identification of patients at high risk of recurrence and unfavorable prognosis. Significance: There is still no general consensus on molecular markers for deciding the appropriateness of adjuvant treatment of early‐stage melanoma. We have shown for the first time that the combined determination of the ctDNA BRAFmut oncogene (liquid biopsy) and the high level of tumor marker S100B in pre‐ and postoperative plasma samples can identify patients with the worst prognosis and the highest risk of tumor recurrence. Therefore, modern adjuvant therapy would be appropriate for these patients with resectable melanoma, regardless of disease stage. [ABSTRACT FROM AUTHOR]

Background: FOXC1 and ERK1‐2 are proteins implicated in aggressive biological behavior of various malignancies including lymphomas. Material and Methods: We investigate the additive prognostic value of stromal FOXC1 expression and tumor phosphorylated ERK1‐2 (pERK1‐2) expression to the established National Comprehensive Cancer Network International Prognostic Index (NCCN‐IPI), in 92 diffuse large B‐cell lymphoma (DLBCL) cases. Multidimensional analysis using statistics and machine learning (ML) models assessed prognostic value of established clinicopathologic variables with stromal FOXC1 and tumor pERK1‐2 expressions. Results: Both high FOXC1 stroma group and high pERK1‐2 tumor group were significantly associated with shorter progression‐free survival (PFS) and overall survival (OS) compared with low group (p = 0.015, 0.034 and p = 0.025, 0.025 each respectively). In multivariable analysis, high FOXC1 stromal expression was an independent prognostic factor of OS (p = 0.037). The addition of stromal FOXC1 and tumor pERK1‐2 to the NCCN‐IPI score significantly improved prediction of time to death compared with NCCN‐IPI score alone (Harrell's C‐index = 0.801 vs. 0.764; p = 0.030). ML models reconfirmed the addition of stromal FOXC1 expression and tumor pERK1‐2 to NCCN‐IPI score had the highest C‐index (0.952) among combinations. Stromal FOXC1 and tumor pERK1‐2 were determinants of DLBCL prognosis, whose addition significantly improved prognostic performance of the NCCN‐IPI. [ABSTRACT FROM AUTHOR]

Background: Lung cancer (LC) is the leading cause of cancer-related deaths. Although low-dose computed tomography (LD-CT) reduces mortality, its clinical use is limited by cost, radiation, and false positives. Therefore, there is an urgent need for non-invasive and cost-effective biomarkers. The Raf Kinase Inhibitor Protein (RKIP) plays a crucial role in cancer development and progression and may also contribute to regulating the tumor–immune system axis. This protein has recently been described in biological fluids. Therefore, we conducted a pilot case–control study to assess RKIP and phosphorylated RKIP (pRKIP) levels in the urine and blood of LC patients. Methods: A novel enzyme linked immunosorbent assay (ELISA) assay was used to measure RKIP and pRKIP levels in urine and blood samples of two cohorts of LC patients and healthy controls (HSs). Furthermore, the biomarkers levels were correlated with tumor characteristics. Results: Serum, but not urine, levels of RKIP were significantly elevated in LC patients, distinguishing them from low- and high-risk healthy subjects with 93% and 74% accuracy, respectively. The RKIP/pRKIP ratio (RpR score) showed an accuracy of 90% and 79% in distinguishing LC patients from HS and HR-HS, respectively. Additionally, the RpR score correlated better with dimension, stage, and lymph node involvement in the tumor group. Conclusions: The serum RKIP and pRKIP profile may be a promising novel biomarker for early-stage LC. [ABSTRACT FROM AUTHOR]

C10orf90, a tumor suppressor, can inhibit the occurrence and development of tumors. Therefore, we investigated the gene function of C10orf90 in various tumors using multiple pan-cancer datasets. Pan-cancer analysis results reveal that the expression levels of C10orf90 vary across different tumors and hold significant value in the clinical diagnosis and prognosis of patients with various tumors. In some cancers, the expression level of C10orf90 is correlated with CNV, DNA methylation, immune subtypes, immune cell infiltration, and drug sensitivity in the tumors. In particular, in COAD, the C10orf90 gene is implicated in multiple processes associated with COAD. Cell experiments demonstrate that C10orf90 suppresses the proliferation and migration of colon cancer cells while promoting apoptosis. In summary, C10orf90 plays a role in the onset and progression of various cancers and could potentially serve as an effective diagnostic and prognostic marker for cancer patients. Notably, in COAD, C10orf90 inhibits the proliferation and migration of colon cancer cells, induces apoptosis, and is linked to the advancement of colon cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: T-cell lymphomas are hematologic cancers that are difficult to manage due to their aggressive nature and poor response to traditional chemotherapies. Response rates are unpredictable even in the era of novel therapeutics, and there has yet to be a clinically validated cellular marker associated with response rates or treatment outcomes. CD5 is a cellular marker that has been associated with poor outcomes in other cancers but has not been well established in T-cell lymphoma. This study confirmed that CD5 has a high prevalence in T-cell lymphomas and is associated with poor prognostic markers such as advanced age, bone marrow involvement, and poor functional status. Additionally, CD5 was associated with inferior survival in T-follicular cell lymphoma and adult T-cell lymphoma. These results suggest that CD5 is associated with worse prognosis in T-cell lymphomas and may be a potential therapeutic target in future studies. Background: T-cell lymphomas (TCLs) are a group of heterogenous cancers with poor rates and duration of response. There remains a great challenge in risk stratification of these cancers. Cluster of differentiation (CD) 5 has shown prognostic implication in many subtypes of B-cell lymphoma; however, its role in TCLs is not known. Methods: We performed a single-institution retrospective analysis of newly diagnosed patients with TCL. CD5 positivity was determined based on positive results via immunohistochemistry and/or flow cytometry. We used univariate and multivariable analysis of biological factors to assess their association with survival outcomes. Results: A total of 194 patients with TCL spanning 14 subtypes were identified. CD5 positivity was noted in 63% of patients, with the highest proportion of CD5 expression in TFH TCL (93.9%), PTCL-NOS (82.9%), and ATLL (77.8%) (p = 0.00004). Older age at diagnosis (p = 0.001), stage III or IV disease (p = 0.05), and bone marrow involvement (p = 0.003) were also associated with CD5 expression. Complete response rates were numerically lower in patients with CD5+ TCL across all subtypes. OS/PFS was not statistically associated with CD5 status in the overall cohort; however there was significantly decreased OS in CD5+ TFH TCL (p = 0.04) and CD5+ ATLL (p = 0.04) patients. Conclusions: This study represents the first to examine CD5 expression as a prognostic biomarker for outcomes in TCL. The frequent expression of CD5 in the most common nodal TCL in the Western world underpins its potential as an attractive target for cellular therapies. Confirmation of these findings in a larger cohort and investigation of potential pathophysiological mechanisms explaining our observations are planned. [ABSTRACT FROM AUTHOR]

Simple Summary: This study assessed the prognostic impact of sarcopenic obesity (SO) in colorectal cancer patients. Among 211 sarcopenic patients, those with obesity (SO group) demonstrated significantly shorter cancer-related relapse-free survival (CRRFS) compared to their non-obese counterparts (non-SO group). While cancer-specific survival (CSS) was also poorer in the SO group, this difference did not reach statistical significance. Additionally, there was no significant difference in overall survival (OS) between the two groups. Multivariate analysis identified sarcopenic obesity, elevated CEA levels, and unfavorable histological types as independent predictors of poor CRRFS. These findings underscore the importance of routine assessment of both sarcopenia and obesity in clinical practice. Moreover, they highlight the potential benefits of interventions aimed at increasing muscle mass and reducing visceral fat to enhance patient outcomes. Background: Sarcopenia, the age-related loss of muscle mass, is a negative prognostic factor in gastrointestinal cancer. Sarcopenia combined with visceral obesity (sarcopenic obesity) is associated with poor outcomes. We explored the influence of obesity and other factors on the prognosis of patients with colorectal cancer diagnosed with sarcopenia. Methods: We enrolled 211 patients with colorectal cancer diagnosed with preoperative sarcopenic obesity who underwent radical resection at Osaka University Hospital between January 2009 and January 2012. Muscle mass was assessed using the psoas muscle mass index. Obesity was evaluated by measuring the visceral fat area in the umbilical region. Patients were categorized into two groups: sarcopenia with obesity (SO) and sarcopenia without obesity (non-SO). Overall survival, cancer-specific survival, and cancer-related relapse-free survival (CRRFS) were compared between the two groups. Patient characteristics, including age, sex, body mass index, serum albumin, C-reactive protein, tumor markers, prognostic nutritional index (PNI), modified Glasgow prognostic score (mGPS), and geriatric nutritional risk index (GNRI), were also analyzed. Results: CRRFS was significantly shorter in the SO group than in the non-SO group (p = 0.028). PNI, mGPS, and GNRI were not identified as significant prognostic factors for CRRFS. Multivariate analysis highlighted sarcopenic obesity, elevated carcinoembryonic antigen levels, and unfavorable histological types as significant predictors of poor CRRFS outcomes. Conclusions: Sarcopenic obesity is an independent predictor of poor prognosis in patients with CRC. Thus, interventions aimed at increasing muscle mass and reducing visceral fat could potentially improve the prognosis of these patients. [ABSTRACT FROM AUTHOR]

Simple Summary: In this study, we developed an mRNA cancer vaccine by encapsulating melanoma-associated antigen A3 (MAGE-A3) mRNA in lipid nanoparticles made of O,O′-dimyristyl-N-lysyl aspartate (DMKD) and phosphatidylserine (PS). These nanoparticles demonstrated stability, preserving mRNA integrity even after extended refrigeration. Immunization with this vaccine significantly inhibited tumor growth in mice and activated strong immune responses. This suggests that the MAGE-A3 mRNA vaccine using DMKD-PS nanoparticles could provide both therapeutic and preventive benefits for tumors associated with this antigen. Cancer causes over 10 million deaths annually worldwide and remains a significant global health challenge. This study investigated advanced immunotherapy strategies, focusing on mRNA vaccines that target tumor-specific antigens to activate the immune system. We developed a novel mRNA vaccine using O,O′-dimyristyl-N-lysyl aspartate (DMKD) to improve stability and phosphatidylserine (PS) to enhance antigen presentation to immune cells. This vaccine, containing melanoma-associated antigen A3 (MAGE-A3) mRNA encapsulated within lipid nanoparticles (LNPs), was evaluated for its therapeutic potential against colorectal cancer. Our findings demonstrated that MAGE-A3 mRNA-containing DMKD-PS LNPs significantly reduced tumor size and weight, effectively combating metastatic cancer. The vaccine elicited a robust immune response, increasing specific immunoglobulin and cytokine levels without causing histotoxicity in major organs. These results confirm that the DMKD-PS-based MAGE-A3 mRNA vaccine holds promise for cancer prevention and treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: Brachytherapy is a form of internal radiation therapy where radioactive sources are placed directly in or near tumors. This paper shows how brachytherapy can be personalized using new technologies like 3D-printed applicators, advanced imaging techniques, and artificial intelligence to make treatment more precise and effective. The authors also explore the role of genetic tests and biomarkers for choosing the best treatments for each patient, as well as future approaches such as combining brachytherapy with immunotherapy and developing new ways to shape radiation doses using shielding. By tailoring treatments to individual patients, personalized brachytherapy aims to effectively treat cancer while reducing treatment-related side effects. Brachytherapy offers a highly conformal and adaptive approach to radiation therapy for various oncologic conditions. This review explores the rationale, applications, technological advances, and future directions of personalized brachytherapy. Integration of advanced imaging techniques, 3D-printed applicators, and artificial intelligence are rapidly enhancing brachytherapy delivery and efficiency, while genomic tests and molecular biomarkers are refining patient and dose selection. Emerging research on combining brachytherapy with immunotherapy offers unique synergistic potential, and technologies such as intensity-modulated and shielded brachytherapy applicators present novel opportunities to further optimize dose distributions. Despite these promising advances, the field faces challenges including a need to train more practitioners and develop new approaches to treating a broader range of malignancies. As personalized medicine evolves, brachytherapy's ability to deliver highly targeted, individualized treatments positions it as a critical component in future cancer care. [ABSTRACT FROM AUTHOR]

Simple Summary: Although immunotherapy is well established for treating pleural mesothelioma, it has not shown a breakthrough in improving the overall survival of these patients. A detailed study of the tumor microenvironment could lead to a better understanding of the factors that influence tumor growth to optimize treatment. In our cohort, T cell infiltrate differences were strongly associated with overall survival. Background: Immunotherapy has significantly improved overall survival in patients with pleural mesothelioma, yet this benefit does not extend to those with the epithelioid subtype. Tumor growth is believed to be influenced by the immune response. This study aimed to analyze the tumor microenvironment to gain a better understanding of its influence on tumor growth. Methods: The tumor immune cell infiltration of 188 patients with pleural mesothelioma was characterized by multiplex immunofluorescence staining for CD3+ cells (CD3+), CD4+ cells (CD3+/CD4+), CD8+ cells (CD3+/CD8+), Treg (CD3+/CD4+/CD8-/CD163-/Foxp3+), PD1 cells (PD1+), and T helper cells (CD3+/CD4+/CD8-/CD163-/FoxP3-). The distribution of specific immune cells was correlated with clinical parameters. Results: A total of 188 patients with pleural mesothelioma (135 epithelioid, 9 sarcomatoid, 44 biphasic subtypes) were analyzed. The median age was 64.8 years. Overall survival was significantly longer in the epithelioid subtype than in the non-epithelioid subtype (p = 0.016). The presence of PD-L1 expression had a negative effect on overall survival (p = 0.041). A high ratio of CD4+ cells to regulatory T cells was associated with a significantly longer overall survival of more than 12 months (p = 0.015). The ratio of CD4+ cells to regulatory T cells retained its significant effect on overall survival in the multivariate analysis. Conclusions: Distinct differences in the T cell immune infiltrates in mesothelioma are strongly associated with overall survival. The tumor microenvironment could therefore serve as a source of prognostic biomarkers. [ABSTRACT FROM AUTHOR]

Simple Summary: The OncoIndx® platform is an NGS assay designed and developed to identify critical mutations that help in therapeutic decision-making. The OncoIndx® panel targets major exons and a few selected introns of 1080 cancer-associated and actionable genes. The test analyzes complex biomarkers such as single nucleotide variants (SNVs), copy number alterations (CNAs), specific gene fusions, and many more. This study validates the overall sensitivity and efficiency of the test using standard references, clinical samples, and U.S. Food and Drug Administration (FDA)-approved cross-laboratory samples. The ultimate goal of this research is to benchmark the assay against the current guidelines and increase the reliability of the test, thus increasing the confidence of medical professionals for better personalized therapeutic intervention. Comprehensive next-generation sequencing (NGS) assays enable the identification of clinically relevant mutations, enhancing the capability for targeted therapeutic interventions. In addition, genomic alterations driving the oncogenic roadmap and leading to resistance mechanisms are reshaping precision oncology. We report the workflow and clinical and technical validation of the OncoIndx® NGS platform—a comprehensive genomic profiling (CGP)-based assay for pan-cancer investigation. We evaluated the concordance between the OncoIndx® test findings and clinically established hotspot detection using SeraSeq reference standards. OncoIndx is a hybridization capture-based NGS assay for the targeted deep sequencing of all exons and selected introns of 1080 cancer-related genes. We show the outcome in the form of tier I and tier II single nucleotide variants (SNVs), copy number alterations (CNAs), and specific gene fusions. OncoIndx® also informs genome-wide tumor mutational burden (TMB), microsatellite instability (MSI), homologous recombination deficiency (HRD), and genomic loss of heterozygosity (gLOH). A total of 63 samples were utilized for validation with reference standards, clinical samples, and orthogonal assessment for genomic alterations. In addition, 49 cross-laboratory samples were validated for microsatellite instability (MSI), and for the tumor mutation burden (TMB), 18 samples as reference standards, 6 cross-laboratory samples, and 29 TCGA samples were utilized. We show a maximum clinical sensitivity of 98% and a positive predictive value (PPV) of 100% for the clinically actionable genomic variants detected by the assay. In addition, we demonstrate analytical validation with the performance of the assay, limit of detection (LoD), precision, and orthogonal concordance for various types of SVs, CNAs, genomic rearrangements, and complex biomarkers like TMB, MSI, and HRD. The assay offers reliable genomic predictions with the high-precision detection of actionable variants, validated by established reference standards. [ABSTRACT FROM AUTHOR]

Simple Summary: The tumor microenvironment (TME) refers to the area immediately surrounding a cancerous tumor that influences the tumor's behavior and how the immune system reacts to it. Central to the TME environment are special immune cells—tumor-associated macrophages (TAMs)—that, rather than restrict the tumor, actually facilitate tumor growth and metastasis. Thus, targeting these TAMs can help to eliminate cancer. In this article, we review the biology of TAMs and delve into the signaling mechanisms underlying the polarization of macrophage phenotypes, their plasticity, and therapeutic implications. Within the tumor microenvironment, myeloid cells constitute a dynamic immune population characterized by a heterogeneous phenotype and diverse functional activities. In this review, we consider recent literature shedding light on the increasingly complex biology of M2-like immunosuppressive tumor-associated macrophages (TAMs), including their contribution to tumor cell invasion and metastasis, stromal remodeling (fibrosis and matrix degradation), and immune suppressive functions, in the tumor microenvironment (TME). This review also delves into the intricate signaling mechanisms underlying the polarization of diverse macrophage phenotypes, and their plasticity. We also review the development of promising therapeutic approaches to target these populations in cancers. The expanding knowledge of distinct subsets of immunosuppressive TAMs, and their contributions to tumorigenesis and metastasis, has sparked significant interest among researchers regarding the therapeutic potential of TAM depletion or phenotypic modulation. [ABSTRACT FROM AUTHOR]

Simple Summary: This research was conducted to evaluate the impact of ipilimumab treatment in patients with metastatic melanoma when monotherapy with PD-1 inhibitors has failed. In particular, the aim was to evaluate the efficacy of ipilimumab in this setting based on the presence or absence of BRAF or NRAS mutations. The present study could allow us to understand when salvage treatment with ipilimumab would have the best impact, although an analysis on a larger patient cohort would be necessary. Background: When monotherapy with PD-1 inhibitors in metastatic melanoma fails, there are currently no standard second-line choices. In case of the unavailability of clinical trials, ipilimumab represents a possible alternative treatment. Methods: We collected data of 44 patients who received ipilimumab after the failure of PD-1 inhibitors from July 2017 to May 2023 at our Institute. Overall survival (OS), progression-free survival (PFS), and post-progression survival (PPS) based on BRAF or NRAS mutation status, sex, and the presence of brain metastases were estimated using the Kaplan–Meier method. Cox regression was used to evaluate independence in multivariate analysis. The objective response rate (ORR) was estimated based on RECIST 1.1. Results: Among the 44 patients enrolled in this study, 28 BRAF-wildtype, 9 BRAF-mutated, and 7 NRAS-mutated patients were identified. OS analysis showed a significant difference between wildtype and BRAF- or NRAS-mutated patients: 23.2 months vs 5.3 and 4.59, respectively, p = 0.017. The presence of brain metastases and BRAF or NRAS mutation were independent factors for mortality in multivariate analysis. Conclusions: In case of failure to enroll patients in innovative clinical trials, second-line ipilimumab still represents an effective therapy in patients with metastatic wildtype melanoma and in the absence of brain metastases. [ABSTRACT FROM AUTHOR]

Simple Summary: The characterization of molecular alterations is continuously gaining relevance in pathology as it can contribute to explaining tumors' pathogenesis and address specific targeted therapies. As for the kidney, in recent years, much scientific research has been focused on the MiTF family genes, particularly on the TFE3 gene. In this setting, while initially just accustomed to a subtype of renal cell carcinoma, currently classified as TFE3-rearranged renal cell carcinoma, TFE3 fusions have been identified in a few mesenchymal neoplasms of the kidney viewed as PEComas. In this work, we gather the available data regarding the key clinical and pathological features of these TFE3-rearranged renal epithelial and mesenchymal neoplasms. We seek to propose a comprehensive solution regarding their pathogenesis and sort out their classification conundrum. Background: Identical translocations involving the TFE3 gene and various partners have been found in both renal and soft tissue tumors, like alveolar soft part sarcoma (ASPSCR1), ossifying fibromyxoid tumor (PHF1), epithelioid hemangioendothelioma, and the clear cell stromal tumor of the lung (YAP1). Methods: Herein, we review in detail the clinicopathologic and molecular data of TFE3-rearranged renal tumors and propose our perspective, which may shed light on this emerging conundrum. Results: Among the kidney tumors carrying TFE3 translocations, most are morphologically heterogeneous carcinomas labeling for the tubular marker PAX8. The others are mesenchymal neoplasms known as PEComas, characterized by epithelioid cells co-expressing smooth muscle actin, cathepsin-K, melanogenesis markers, and sometimes melanin pigment deposition. Over the past 30 years, numerous TFE3 fusion partners have been identified, with ASPL/ASPSCR1, PRCC, SFPQ/PSF, and NONO being the most frequent. Conclusions: It is not well understood why similar gene fusions can give rise to renal tumors with different morpho-immunophenotypes, which may contribute to the recent disagreement regarding their classification. However, as these two entities, respectively, epithelial and mesenchymal in nature, are widely recognized by the pathology community and their clinicopathologic features well established, we overall believe it is still better to retain the names TFE3-rearranged renal cell carcinoma and TFE3-rearranged PEComa. [ABSTRACT FROM AUTHOR]

Simple Summary: There has recently been an interest in drugs that work across the pan-cancer spectrum and show antitumor activity based on biomarkers rather than histology. In this article, we discuss one of these biomarkers, NTRK fusions, which, if present, can predict sensitivity to treatment with inhibitors of the NTRK molecular pathway. Currently, there are three drugs that have been approved by the United States Food and Drug Administration (FDA) in patients with NTRK fusions, regardless of the tumor tissue of origin. These are larotrectinib, entrectinib, and repotrectinib. Herein, we discuss what NTRK fusions are and how to detect them, alongside data on each drug, from a clinical perspective. NTRK fusions are oncogenic drivers for multiple tumor types. Therefore, the development of selective tropomyosin receptor kinase (TRK) inhibitors, including larotrectinib and entrectinib, has been transformative in the context of clinical management, given the high rates of responses to these drugs, including intracranial responses in patients with brain metastases. Given their promising activity in pan-cancer cohorts, larotrectinib and entrectinib received U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) approval for tissue-agnostic indications in patients with advanced solid tumors harboring NTRK fusions. The safety profiles for both drugs are quite manageable, although neurotoxicity driven by the on-target inhibition of normal NTRK can be a concern. Also, on- and off-target resistance mechanisms can arise during therapy with TRK inhibitors, but they can be addressed with the use of combination therapy and next-generation TRK inhibitors. More recently, the FDA approved the use of repotrectinib, a second-generation TRK inhibitor, in patients with NTRK fusions, based on data suggesting clinical efficacy and safety, which could offer another tool for the treatment of NTRK-altered cancers. In this review, we summarize the current evidence related to the use of TRK inhibitors in the tissue-agnostic setting. We also elaborate on the safety profiles and resistance mechanisms from a practical perspective. [ABSTRACT FROM AUTHOR]

Simple Summary: Pancreatic cancer is surrounded by a dense fibrotic environment due to the activity of pancreatic stellate cells (PSCs). This hinders the effectiveness of treatment by limiting drug penetration and oxygen delivery. To better understand this, PSCs and cancer cells were studied in laboratory models using radiotracer imaging techniques. The results indicated that while glucose uptake and hypoxia were similar between cancer cells alone and in combination with PSCs, a specific marker of fibrosis (FAPα) was significantly higher in PSC-rich environments. In mice, the marker in question decreased in tumors with only PSCs, indicating that the cells had died. Conversely, the biomarker increased over time in tumors containing both cancer cells and PSCs, suggesting that mouse cells had invaded. This study sheds light on how the tumor environment influences metabolism and thus provides insights for more targeted theranostic applications. In turn, this approach supports the development of more reliable models. Background/Objective Pancreatic stellate cells (PSCs) in pancreatic adenocarcinoma (PDAC) are producing extracellular matrix, which promotes the formation of a dense fibrotic microenvironment. This makes PDAC a highly heterogeneous tumor-stroma-driven entity, associated with reduced perfusion, limited oxygen supply, high interstitial fluid pressure, and limited bioavailability of therapeutic agents. Methods In this study, spheroid and tumor xenograft models of human PSCs and PanC-1 cells were characterized radiopharmacologically using a combined positron emission tomography (PET) radiotracer approach. [18F]FDG, [18F]FMISO, and [18F]FAPI-74 were employed to monitor metabolic activity, hypoxic metabolic state, and functional expression of fibroblast activation protein alpha (FAPα), a marker of activated PSCs. Results In vitro, PanC-1 and multi-cellular tumor spheroids demonstrated comparable glucose uptake and hypoxia, whereas FAPα expression was significantly higher in PSC spheroids. In vivo, glucose uptake as well as the transition to hypoxia were comparable in PanC-1 and multi-cellular xenograft models. In mice injected with PSCs, FAPα expression decreased over a period of four weeks post-injection, which was attributed to the successive death of PSCs. In contrast, FAPα expression increased in both PanC-1 and multi-cellular xenograft models over time due to invasion of mouse fibroblasts. Conclusion The presented models are suitable for subsequently characterizing stromal cell-induced metabolic changes in tumors using noninvasive molecular imaging techniques. [ABSTRACT FROM AUTHOR]

Simple Summary: Breast cancer is diagnosed in 2.3 million women each year and kills 685,000 (~30% of patients) worldwide. The most dangerous breast cancer is triple-negative breast cancer (TNBC). TNBC is very diverse, with 12 underlying subtypes. This great deal of patient diversity, along with the lack of broad-application targetable mechanistic markers (such as ER, PR, and HER2, which are present in other breast cancer subtypes but missing in TNBC), gives TNBC patients the worst outcomes of any breast cancer type. We aim to remedy this by exploring the molecular mechanisms across TNBC samples and subtypes. Molecular mechanisms are potentially targetable for treatment. We explore these options as part of our RNA-sequencing analysis. Our novel findings include highly accurate mechanistic markers identified using machine learning methods, including CIDEC (97.1% accuracy alone). Additionally, we found TNBC subtype-differentiating mechanistic markers, including PDE3B, CFD, IFNG, and ADM, which are targets with known therapeutics and potential for drug repurposing. Background/Objectives: Breast cancer is diagnosed in 2.3 million women each year and kills 685,000 (~30% of patients) worldwide. The prognosis for many breast cancer subtypes has improved due to treatments targeting the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). In contrast, patients with triple-negative breast cancer (TNBC) tumors, which lack all three commonly targeted membrane markers, more frequently relapse and have lower survival rates due to a lack of tumor-selective TNBC treatments. We aim to investigate TNBC mechanistic markers that could be targeted for treatment. Methods: We performed a secondary TNBC analysis of 196 samples across 10 publicly available bulk RNA-sequencing studies to better understand the molecular mechanism(s) of disease and predict robust mechanistic markers that could be used to improve the mechanistic understanding of and diagnostic capabilities for TNBC. Results: Our analysis identified ~12,500 significant differentially expressed genes (FDR-adjusted p-value < 0.05), including KIF14 and ELMOD3, and two significantly modulated pathways. Additionally, our novel findings include highly accurate mechanistic markers identified using machine learning methods, including CIDEC (97.1% accuracy alone), CD300LG, ASPM, and RGS1 (98.9% combined accuracy), as well as TNBC subtype-differentiating mechanistic markers, including the targets PDE3B, CFD, IFNG, and ADM, which have associated therapeutics that can potentially be repurposed to improve treatment options. We then experimentally and computationally validated a subset of these findings. Conclusions: The results of our analyses can be used to better understand the mechanism(s) of disease and contribute to the development of improved diagnostics and/or treatments for TNBC. [ABSTRACT FROM AUTHOR]

Simple Summary: Adjuvant chemotherapy (AC) using S-1 has demonstrated favorable outcomes for patients with pancreatic cancer (PC). However, the current S-1 completion rate is insufficient to achieve its benefits. Moreover, an absence of dependable markers to forecast S-1 completion warrants C-reactive protein-to-albumin ratio (CAR) investigation as a potential predictive factor related to nutritional status. Previously, we revealed that a postoperative CAR value of ≥0.05 serves as a marker predicting S-1 AC treatment non-completion due to adverse events (AEs) in the Ehime study. Thus, this study aims to substantiate the correlation between postoperative CAR and S-1 therapy non-completion due to AEs using an alternative cohort from another institution (the Dokkyo study). Background: S-1 in adjuvant chemotherapy (AC) administration after pancreatic cancer (PC) surgery has been standardized in Japan. The Ehime study confirmed that a postoperative higher C-reactive protein-to-albumin ratio (CAR) value predicted the risk of adverse event (AE)-related S-1 non-completion as an AC in patients with PC after curative surgery. This study aimed to investigate the index to predict S-1 tolerance among patients who underwent curative surgery for PC (the Dokkyo study). Methods: This retrospective validation cohort study included 172 patients at the Department of Hepato-Biliary Pancreatic Surgery, Dokkyo Medical University, Japan, from January 2010 to December 2022. All patients underwent nutritional screening using the postoperative CAR. S-1 completion status and its effect on prognosis were systematically followed up and investigated. We conducted a statistical analysis of predictive markers to investigate their association with S-1 completion. Results: Patients were categorized into the S-1 completion (N = 91) and non-completion (N = 81) groups. The S-1 completion group demonstrated a significantly lower CAR than the S1 non-completion group. Moreover, the current study revealed a significant difference in the S-1 completion rate, applying the CAR cutoff value of 0.05 established in the Ehime study. Additionally, univariate and multivariate analyses confirmed that a CAR of <0.05 was significantly associated with S-1 completion. Conclusions: The Dokkyo study confirmed the results observed in the Ehime study. Consequently, an increased postoperative CAR value appeared as a universal applicable marker for the risk factor of AE-related S-1 non-completion after curative surgery for patients with PC. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer affects millions worldwide, with gastrointestinal cancers being notably common. This review explores the potential of telomeres and telomerase as biomarkers for diagnosing and predicting these cancers. Telomeres are protective caps at chromosome ends that shorten with cell division, while telomerase helps extend them. Changes in these markers could indicate cancer risk and progression. Despite efforts to prevent cancer through lifestyle changes, gastrointestinal cancers such as colorectal and gastric cancer remain prevalent. Current detection methods like endoscopy are invasive, driving interest in non-invasive alternatives. By consolidating research on telomere length and telomerase activity, this review aims to highlight how these biomarkers could enhance early diagnosis and monitoring. Understanding these mechanisms better could lead to improved diagnostic tools and therapeutic strategies, potentially refining how gastrointestinal cancers are managed and improving patient outcomes. Gastrointestinal (GI) cancers, such as colorectal and gastric cancers, pose significant global health challenges due to their high rates of incidence and mortality. Even with advancements in treatment and early detection, many patients still face poor outcomes, highlighting the critical need for new biomarkers and therapeutic targets. Telomere length (TL) and telomerase activity (TA) have gained attention in this context. Telomeres, protective nucleotide sequences at chromosome ends, shorten with each cell division, leading to cellular aging. Telomerase, a ribonucleoprotein enzyme, counteracts this shortening by adding telomeric repeats, a process tightly regulated in normal cells but often dysregulated in cancer. This review critically evaluates the role of TL and TA in the pathogenesis of GI cancers, examining their potential as diagnostic, prognostic, and predictive biomarkers. It explores how alterations in telomere biology contribute to the initiation and progression of GI tumors and assesses the therapeutic implications of targeting telomerase. By integrating findings from diverse studies, this review aims to elucidate the intricate relationship between telomere dynamics and gastrointestinal carcinogenesis, offering insights into how TL and TA could be leveraged to enhance the early detection, treatment, and prognosis of GI cancers. [ABSTRACT FROM AUTHOR]

Simple Summary: This study aimed to identify prognostic factors by combining clinicopathologic parameters with tumor microenvironment (TME) biomarkers in patients with locally advanced rectal cancer (LARC) who underwent surgery following neoadjuvant chemoradiotherapy (nCRT). We analyzed CD8+ T cells, CXCR3, CXCL10, and α-SMA using immunohistochemical staining and incorporated AI-powered digital pathology to assess the spatial TME. Our findings showed that high expression of CD8+ T cells, CXCR3 in tumor-infiltrating lymphocytes (TILs), and an inflamed phenotype were associated with better recurrence-free survival (RFS). However, these factors were not predictive of overall survival (OS). Patients with an immune-desert phenotype had a poor prognosis regardless of pathologic stage or the administration of postoperative chemotherapy. These results suggest that CD8+ T cells and AI-powered immune phenotypes, together with clinical factors, can guide personalized treatment strategies in LARC patients post-nCRT and highlight the potential benefits of modifying the tumor immune microenvironment (TiME) to reduce recurrence after surgery. Background/Objectives: The tumor microenvironment (TME) has emerged as a significant prognostic factor. This study aimed to identify prognostic factors by combining clinicopathologic parameters and the TME biomarkers in patients who underwent surgery following neoadjuvant chemoradiotherapy (nCRT) for locally advanced rectal cancer (LARC). Methods: CD8+ T cells, CXCR3, CXCL10, and α-smooth muscle actin (α-SMA) were analyzed via immunohistochemical staining. We also incorporated AI-powered digital pathology to assess the spatial TME. The associations between these biomarkers, clinicopathologic parameters, and survival outcomes were evaluated. Results: CD8+ T cell expression, CXCR3 expression in tumor-infiltrating lymphocytes (TILs), and immune phenotypes were correlated. LARC patients with a high expression of CD8+ T cells, CXCR3 in TILs, and an inflamed phenotype had a significantly better prognosis than their counterparts did. In the multivariate analysis, the expression of CD8+ T cells and the inflamed/immune-excluded phenotype were significant tumor immune microenvironment (TiME) biomarkers for recurrence-free survival (RFS) but not for overall survival (OS). Notably, patients with the immune-desert phenotype had a poor prognosis regardless of pathologic stage, even if postoperative chemotherapy was administered (p < 0.001). Conclusions: CD8+ T cells and AI-powered immune phenotypes, alongside clinical factors, can guide personalized treatment in LARC patients receiving nCRT. A therapeutic strategy to modify the TiME after nCRT could help reduce recurrence after surgery. [ABSTRACT FROM AUTHOR]