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Abstract DNA damage is considered to be a potentially unifying driver of ageing, and the stalling of DNA damage repair accelerates the cellular senescence. However, augmenting DNA repair has remained a great challenge due to the intricate repair mechanisms specific for multiple types of lesions. Herein, we miniaturized our modified detecting system for homologous recombination (HR) into a 96-well-based platform and performed a high-throughput chemical screen for FDA-approved drugs. We uncovered that amodiaquine could significantly augment HR repair at the noncytotoxic concentration. Further experiments demonstrated that amodiaquine remarkably suppressed stress-induced premature cellular senescence (SIPS), as evidenced by senescence-associated beta-galactosidase (SA-β-gal) staining or senescence‐related markers p21WAF1 and p16ink4a, and the expression of several cytokines. Mechanistic studies revealed that the stimulation of HR repair by amodiaquine might be mostly attributable to the promotion of SIRT1 at the transcriptional level. Additionally, SIRT1 depletion abolished the amodiaquine‐mediated effects on DNA repair and cellular senescence, indicating that amodiaquine delayed the onset of SIPS via a SIRT1-dependent pathway. Taken together, this experimental approach paved the way for the identification of compounds that augment HR activity, which could help to underscore the therapeutic potential of targeting DNA repair for treating aging-related diseases.

Abstract This study was to determine the involvement of long non‐coding RNA C7orf13 in nasopharyngeal carcinoma (NPC) and its underlying mechanism. Real‐time quantitative PCR results indicated that C7orf13 was overexpressed in NPC and associated with malignant features. C7orf13 knockdown significantly suppressed the proliferation, migration and invasion of NPC cells. Furthermore, we found that C7orf13 sequestered miR‐449c and miR‐28‐5p in NPC cells by dual‐luciferase reporter assays and RNA immunoprecipitation analysis. Sequent experiments showed that C7orf13 has a positive relationship with formin‐like 2 (FMNL2) in NPC tissues. Moreover, C7orf13 knockdown weakened FMNL2‐mediated cell invasion and migration. Finally, functional experiments revealed that the positive effect of C7orf13 on cell migration and invasion was mediated by the miR‐449c/miR‐28‐5p‐FMNL2 axis. Generally, our study identifies the biological role of long non‐coding RNA C7orf13 in the malignant process of NPC, which may pave a new way for the diagnosis and treatment of NPC.

Background: Esophageal cancer (EC) remains a global health challenge due to its poor prognosis. China and the United States of America (USA) represent two distinct epicenters of EC burden. Understanding the EC disparities in these two countries is vital for tailoring prevention strategies, optimizing treatment, and enhancing outcomes in both countries. Yet, there lacks a comprehensive comparison of EC characteristics between the two countries. Methods: In this multicenter, retrospective hospital-based study, we enrolled primary EC patients who received their initial treatment at one of 23 hospitals in China during 2016–2017. Using electronic medical records and cancer registration records, information on demographics, lifestyle, and clinicopathological characteristics (including tumor site, pathology, stage, metastases, differentiation, and treatment) were collected. Additionally, we compared these data with the clinicopathological information of invasive EC patients diagnosed in 2016–2017 from the Surveillance, Epidemiology, and End Results (SEER) database in the USA. Results: A total of 6,658 EC patients in China and 8,555 EC patients in the USA were included finally. 85.5% (n = 5,694) of EC were esophageal squamous cell carcinoma (ESCC) in China, while esophageal adenocarcinoma (EAC) was prominent in the USA (58.9%, n = 5,041). Among EC patients with known staging, the proportion of early stage was higher in China compared to the USA (48.3% vs. 30.5%). Among ESCC patients, early-stage cases were higher in China than in the USA (49.8% vs. 31.8%), while among EAC patients, late-stage cases were higher in China than in the USA (77.3% vs. 68.5%) (all P < 0.001). In China, EC mainly occurred in the middle third (60.2%) of the esophagus, whereas in the USA, it was more common in the lower third (59.9%) of the organ. Compared with EC patients with known metastatic status in the USA, China had fewer cases of lymph node metastases (51.4% vs. 57.7%) and distant metastases (7.9% vs. 33.8%). Regarding treatment, China had more surgical therapy (53.7% vs. 22.6%), less radiotherapy (35.6% vs. 53.3%), and less chemotherapy (46.7% vs. 59.7%) compared to the USA. Conclusions: This study reveals notable disparities in EC between China and the USA, encompassing epidemiological, clinicopathological, and treatment dimensions. These findings provide insight for tailored strategies addressing regional variations in clinicopathological and therapeutic characteristics.

Background and objective: Systemic treatments involving immunotherapy-tyrosine kinase inhibitor (IO-TKI) combinations and TKI monotherapy have significantly improved outcomes for patients with metastatic clear-cell renal cell carcinoma (mccRCC). However, there are no biomarkers for predicting the efficacy of these treatments. Our aim was to investigate the prognostic and therapeutic significance of serum immunoglobulin G (IgG) in patients with mccRCC patients receiving systemic therapy. Methods: We included 318 patients with mccRCC who received TKI or IO-TKI therapy. Patients were classified into groups according to whether they had an increase or decrease in serum IgG after systemic treatment. The association between baseline serum IgG and the objective response rate (ORR) was compared between the groups using a t test. The association of the change in serum IgG with progression-free survival (PFS) and overall survival (OS) was evaluated via Cox proportional-hazards regression, and survival curves were generated using the Kaplan-Meier method. Key findings and limitations: Baseline serum IgG was not significantly associated with ORR (p = 0.055). After 3-mo systemic therapy, 133 patients (42%) exhibited an increase in serum IgG. The group with an IgG increase had significantly poorer median PFS (5.6 vs 16.2 mo; hazard ratio [HR] 3.36, 95% confidence interval [CI] 2.58–4.36; p

Background and objective: Ureteral stones are currently treated with holmium:yttrium-aluminum-garnet (Ho:YAG) laser lithotripsy using rigid and flexible ureteroscopes. This study aims to evaluate the efficacy and safety of semirigid ureteroscopy combined with Ho:YAG laser lithotripsy for treating proximal ureteral stones in real-world studies. Methods: The PubMed, Embase, and Web of Science databases were searched systematically to retrieve all relevant studies up to April 2024. A meta-analysis of the retrieved studies was performed using Stata 14.0 software and expressed as rate, mean difference, and 95% confidence interval (CI). The main outcomes of this meta-analysis were stone-free rate (SFR) and perioperative outcomes including operation time, hospital stay, postoperative ureteral stent placement, auxiliary procedures, and intra- or postoperative complications. Key findings and limitations: A total of 24 studies were included in this study, including 2058 patients with proximal ureteral stones. According to the results of the combined analysis, the SFR of semirigid ureteroscopy combined with Ho:YAG laser lithotripsy for the treatment of proximal ureteral stones was 78% (95% CI [75%, 82%]), operation time was 51.03 min (95% CI [43.5, 58.56]), hospital stay was 1.62 d (95% CI [1.54, 1.70]), auxiliary procedure rate was 20% (95% CI [15%, 25%]), and postoperative complication rate was 16% (95% CI [12%, 22%]). Conclusions and clinical implications: The results of this study show that semirigid ureteroscopic Ho:YAG laser lithotripsy is a commonly used treatment for proximal ureteral calculi, but its efficacy and safety need to be improved further, and its efficacy is not related to the diameter of the endoscope. Patient summary: This study showed that Ho:YAG laser lithotripsy with semirigid ureteroscopes is commonly used for treating ureteral stones. However, its efficacy and safety need to be improved further, and future research should focus on these.

Abstract Background Patients with non‐small‐cell lung cancer (NSCLC) receiving immunotherapy face a potential risk of developing checkpoint inhibitor‐related pneumonitis (CIP). However, there is no clear understanding of the specific link between interstitial lung abnormality (ILA) and CIP in patients with small‐cell lung cancer (SCLC). In addition, the prognosis of SCLC patients with ILA who receive chemoimmunotherapy is uncertain. Our study aimed to investigate the effect of ILA on the occurrence of CIP in SCLC patients receiving first‐line chemoimmunotherapy and to assess its relationship with prognosis. Methods We conducted a retrospective analysis of SCLC patients who received chemoimmunotherapy as a first‐line treatment between January 2018 and April 2024. The diagnosis of ILA was assessed by two experienced pulmonologists based on pretreatment chest computed tomography images. We investigated independent risk factors for CIP using logistic regression analysis and factors affecting PFS and OS using Cox regression analysis. Results A total of 128 patients with SCLC were included in the study. ILA was present in 41 patients (32.03%), and CIP occurred in 16 patients (12.50%). In multivariate logistic regression analysis, previous ILA (OR, 5.419; 95% CI, 1.574–18.652; p = 0.007) and thoracic radiation therapy (TRT) (OR, 5.259; 95% CI, 1.506–18.365; p = 0.009) were independent risk factors for CIP. ILA (HR, 2.083; 95% CI, 1.179–3.681; p = 0.012) and LDH (HR, 1.002; 95% CI, 1.001–1.002; p

The fibroblast growth factor receptor (FGFR) is a crucial receptor tyrosine kinase involved in essential biological processes, including growth, development, and tissue repair. However, FGFR gene mutations, including amplification, fusion, and mutation, can disrupt epigenetics, transcriptional regulation, and tumor microenvironment interactions, leading to cancer development. Targeting these kinase mutations with small molecule drugs or antibodies has shown clinical benefits. For example, erdafitinib is approved for treating locally advanced or metastatic urothelial cancer patients with FGFR2/FGFR3 mutations, and pemigatinib is approved for treating cholangiocarcinoma with FGFR2 fusion/rearrangement. Effective screening of FGFR variant patients is crucial for the clinical application of FGFR inhibitors. Various detection methods, such as polymerase chain reaction, next-generation sequencing, fluorescence in situ hybridization, and immunohistochemistry, are available, and their selection should be based on diagnostic and treatment decision-making needs. Our developed expert consensus aims to standardize the diagnosis and treatment process for FGFR gene mutations and facilitate the practical application of FGFR inhibitors in clinical practice.

Background The AQP4-AS1/miR-4476-ALOX15 regulatory axis was discovered in previous studies. We aimed to investigate the regulatory mechanism of the ferroptosis-related regulator ALOX15 by AQP4-AS1 and miR-4476 in lung adenocarcinoma (LUAD) and find new targets for clinical treatment.

Abstract Background The tumor microenvironment (TME) plays a crucial role in tumorigenesis and tumor progression. This study aimed to identify novel TME-related biomarkers and develop a prognostic model for patients with non-small-cell lung cancer (NSCLC). Methods After downloading and preprocessing data from The Cancer Genome Atlas (TCGA) data portal and Gene Expression Omnibus (GEO) datasets, we classified the molecular subtypes using the “NMF” R package. We performed survival analysis and quantified immune scores between clusters. A Cox proportional hazards model was then constructed, and its formula was produced. We assessed model performance and clinical utility. A prediction nomogram was also constructed and validated. Additionally, we explored the potential regulatory mechanisms of our TME gene signature using Gene Set Enrichment Analysis (GSEA). Results From data processing and univariate Cox regression analysis, 57 TME-related prognostic genes were identified, and two significantly distinct clusters were established. Using Cox regression and Lasso regression, an 18-gene TME-related prognostic model was developed. Patients were stratified into high- and low-risk groups based on the risk score, with survival analysis showing that the low-risk group had significantly better outcomes than the high-risk group (P

Abstract Background Cancer survivors face many challenges in long-term health management, including malnutrition, systemic inflammation, and sleep issues, which significantly affect their survival and quality of life. Methods A prospective cohort study was derived from the National Health and Nutrition Examination Survey from 2005–2018 harboring 1,908 cancer survivors (weighted population, 11,453,293), of whom 688 deaths (220 from cancer mortality, 468 from non-cancer mortality). The Advanced Lung Cancer Inflammation Index (ALI) was used as a measure of nutritional status and systemic inflammation in cancer patients. Weighted multivariable Cox proportional hazards regression models were utilized to explore the independent and combined effects of ALI and sleep quality on mortality outcomes. Results The participants with a high ALI were more likely to be female, aged 40 to 64 years, non-Hispanic white, and have a higher BMI. We observed that elevated ALI levels were associated with decreased risks of all-cause mortality (Hazard ratio [HR] = 0.601, 95% Confidence interval [CI] = 0.521–0.695, P

Abstract Background Cutaneous malignant melanoma is a very aggressive and metastatic form of skin cancer, typically linked with poor outcomes. Advances in genomic analysis have underscored the crucial role of T cells in tumor immunity. Immune checkpoint inhibitors have notably transformed melanoma treatment by boosting T cell activity. Studies of gene expression have found that the phosphatidylinositol-4-phosphate kinase 2A (PIP4K2A) gene is abnormally expressed in various tumors, indicating its potential role in tumor progression. Utilizing single-cell sequencing and machine learning, researchers can now explore the complex interactions between T cells and melanoma cells at a genomic level. This study aimed to investigate the role of the PIP4K2A gene in cutaneous malignant melanoma, with a focus on its influence on T cell-mediated immune responses. Methods Samples from cutaneous melanoma patients were analysed by single-cell transcriptome for differentially expressed genes and signalling pathways associated with cutaneous melanoma. Then, genes were identified and predictive models were built based on the transcriptomic data using machine learning models to assess whether the expression level of PIP4K2A could effectively predict the malignancy and prognosis of cutaneous melanoma. In addition, we also performed drug therapy predictive analysis and immunotherapy analysis.Finally, the critical role of PIP4K2A in cutaneous melanoma was further confirmed by immunohistochemistry. Results The PIP4K2A gene exhibited a significantly elevated expression level in cutaneous malignant melanoma, showing a strong correlation with the clinical stage and patient prognosis. At the therapeutic level, high PIP4K2A expression is less responsive to immunotherapy, and this gene is a risk factor for drug therapy in cutaneous malignant melanoma. Additionally, our experimental outcomes validated this observation. Conclusions The PIP4K2A gene could be a crucial prognostic marker for cutaneous malignant melanoma, as it significantly affects T cell activity within the tumor microenvironment. This study offers essential insights into melanoma pathogenesis and assists in pinpointing new early diagnostic markers and therapeutic targets. Utilizing advanced genomic tools and computational techniques, the research enhances our understanding of T cell dynamics in melanoma, facilitating the development of personalized medicine and more effective immunotherapy strategies.

Abstract Background LncRNAs play essential roles in multiple tumors. However, research on genome-wide lncRNA alterations and their functions in cervical cancer (CC) is limited. This study aims to explore key lncRNAs in CC progression and uncover the molecular mechanisms involved in the development of CC. Methods In this study, we analyzed 30 tissues from CC, cervical intraepithelial neoplasia (CIN), and normal (NOR) using transcriptome sequencing and weighted gene co-expression network analysis to establish gene modules related to the NOR-CIN-CC transition. Machine learning diagnostic models were employed to investigate the role of lncRNAs in this transition. Molecular biological experiments were conducted to elucidate the potential mechanisms of CARMN in CC, with a particular focus on its transcriptional and post-transcriptional regulation of abnormal expression in CC. Results CARMN was identified as a hub gene in two modules significantly associated with the NOR-CIN-CC transition. Analysis using ten machine learning models confirmed its critical role in this progression. The results of RNA-seq, qPCR and RNAScope performed in another cohort of 83 cervical tissues all showed that CARMN was significantly downregulated in CC. CARMN significantly enhanced the interaction between Keap1 and Nrf2, leading to increased ROS levels. The elevated ROS levels suppressed the Akt/mTOR signaling pathway, leading to autophagy arrest via autophagic flux blockade. Additionally, CARMN interacted with TFAP2α to repress MAPK13 transcription, further inhibiting the MAPK cascade. A promoter SNP (rs12517403) was found to increase CC risk (OR = 1.34, 95% CI = 1.11–1.61) and reduce CARMN expression by decreasing SP1 binding. Furthermore, the RNA binding proteins that could modulate CARMN RNA stability were also determined using RNA-pulldown assay. The results demonstrated that YBX1, a component of the coding region instability determinant (CRD)-mediated mRNA stabilization complex, promoted CARMN RNA stability. DHX9, another component of complex, acted as a scaffold to bridge YBX1 and CARMN. Conclusions CARMN exerts an anti-cancer effect in CC progression by inhibiting the Akt-mTOR and MAPK signaling pathways. rs12517403 and the YBX1/DHX9 complex are key mechanisms influencing its transcription and stability in CC cells. CARMN represents a promising biomarker for CC diagnosis and therapeutic target.

Abstract Background The efficacy of immune checkpoint blockade therapy in patients with hepatocellular carcinoma (HCC) remains poor. Although serine‐ and arginine‐rich splicing factor (SRSF) family members play crucial roles in tumors, their impact on tumor immunology remains unclear. This study aimed to elucidate the role of SRSF10 in HCC immunotherapy. Methods To identify the key genes associated with immunotherapy resistance, we conducted single‐nuclear RNA sequencing, multiplex immunofluorescence, and The Cancer Genome Atlas and Gene Expression Omnibus database analyses. We investigated the biological functions of SRSF10 in immune evasion using in vitro co‐culture systems, flow cytometry, various tumor‐bearing mouse models, and patient‐derived organotypic tumor spheroids. Results SRSF10 was upregulated in various tumors and associated with poor prognosis. Moreover, SRSF10 positively regulated lactate production, and SRSF10/glycolysis/ histone H3 lysine 18 lactylation (H3K18la) formed a positive feedback loop in tumor cells. Increased lactate levels promoted M2 macrophage polarization, thereby inhibiting CD8+ T cell activity. Mechanistically, SRSF10 interacted with the 3′‐untranslated region of MYB, enhancing MYB RNA stability, and subsequently upregulating key glycolysis‐related enzymes including glucose transporter 1 (GLUT1), hexokinase 1 (HK1), lactate dehydrogenase A (LDHA), resulting in elevated intracellular and extracellular lactate levels. Lactate accumulation induced histone lactylation, which further upregulated SRSF10 expression. Additionally, lactate produced by tumors induced lactylation of the histone H3K18la site upon transport into macrophages, thereby activating transcription and enhancing pro‐tumor macrophage activity. M2 macrophages, in turn, inhibited the enrichment of CD8+ T cells and the proportion of interferon‐γ+CD8+ T cells in the tumor microenvironment (TME), thus creating an immunosuppressive TME. Clinically, SRSF10 could serve as a biomarker for assessing immunotherapy resistance in various solid tumors. Pharmacological targeting of SRSF10 with a selective inhibitor 1C8 enhanced the efficacy of programmed cell death 1 (PD‐1) monoclonal antibodies (mAbs) in both murine and human preclinical models. Conclusions The SRSF10/MYB/glycolysis/lactate axis is critical for triggering immune evasion and anti‐PD‐1 resistance. Inhibiting SRSF10 by 1C8 may overcome anti‐PD‐1 tolerance in HCC.

Abstract The aim of this study was to investigate the key targets and signaling pathways of paeoniflorin (PF) for the treatment of gastric cancer (GC). First, the differentially expressed genes (DEGs) of gastric cancer were obtained by analyzing GSE118916 Gene Chip, and then the active components of paeoniflorin and their targets of action were found. And the intersection genes of the two were analyzed for target and pathway analysis. In addition, cell viability after PF intervention was detected by CCK-8. Clone formation assay, wound scratch assay, transwell assay were used to detect cell migration and invasion. The qRT-PCR and Western blot methods were used to verify the mechanism of action. The results showed that a total of 286 paeoniflorin targets and 1799 DEGs were obtained. Secondly, we found that PF could treat gastric cancer through RAS/MAPK signaling pathway. In addition, through in vitro cellular experiments, we also found that PF had a significant therapeutic effect on gastric cancer. Therefore, we believe that PF inhibits the proliferation and metastasis of gastric cancer, and its effect may be exerted by regulating the RAS/MAPK signaling pathway. PF is a promising drug for the treatment of gastric cancer. Combined with the in vitro experiments, we found that the therapeutic effect of PF is related to the regulation of the RAS/MAPK signaling pathway, and the results of the present study preliminarily revealed its complex mechanism, which will lay the foundation for future clinical treatment.

Jiajing Li,1 Qi Liu,2 Ting Zhang,2 Qian Du3 1The Diagnostics Laboratory, Affiliated Hospital to Zunyi Medical University, Zunyi, Guizhou, 563000, People’s Republic of China; 2Affiliated Hospital to Zunyi Medical University, Zunyi, Guizhou, 563000, People’s Republic of China; 3Department of Endoscopy and Digestive System, Guizhou Provincial People’s Hospital, Guiyang, Guizhou, 550002, People’s Republic of ChinaCorrespondence: Qian Du, Email DuqianL5@163.comIntroduction: Hepatocellular carcinoma (HCC), a prevalent and aggressive form of cancer, poses significant challenges due to its limited therapeutic options. This study aims to leverage multi-omics data from liver cancer to identify potential therapeutic targets for HCC.Methods: We employed an integrative approach by analyzing various omics datasets related to liver cancer. Through comprehensive data mining and analysis, we identified key genes that are significantly associated with HCC. To gain insights into their biological roles and underlying mechanisms, we constructed gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway networks. Specifically, we focused on genes that exhibited high expression levels in HCC and were correlated with poor patient prognosis. Among these, CDK1 and DLGAP5 emerged as promising candidates and were further investigated for their potential involvement in tumor immune cell infiltration and HCC progression.Results: Our analysis revealed that CDK1 and DLGAP5 are highly expressed in HCC tissues compared to normal liver tissues, and their elevated expression is associated with unfavorable clinical outcomes. Furthermore, through GO and KEGG pathway analyses, we found that these genes are implicated in critical biological processes and signaling pathways relevant to HCC pathogenesis. Notably, CDK1 and DLGAP5 were shown to be associated with tumor immune cell infiltration, suggesting their potential role in modulating the tumor microenvironment and promoting HCC progression.Discussion: These findings provide valuable insights into the development of novel therapeutic approaches for HCC.Keywords: Hepatocellular carcinoma, bioinformatics analysis, DLGAP5, CDK1, immune cell infiltration

Erb‐b2 receptor tyrosine kinase 2 (ERBB2)‐activating mutations are therapeutically actionable alterations found in various cancers, including metastatic breast cancer (MBC). We developed multiplex digital PCR assays to detect and quantify ERBB2 mutations in circulating tumor DNA from liquid biopsies. We studied the plasma from 272 patients with hormone‐receptor‐positive, human epidermal growth factor receptor 2‐negative (HR+/HER2−) MBC to detect 17 ERBB2 mutations using a screening assay. The assay was developed on the three‐color Crystal dPCR™ naica® platform with a two‐step strategy for precise mutation identification. We found that nine patients (3.3%) harbored at least one ERBB2 mutation. The mutation rate was higher in patients with lobular histology (5.9%) compared to invasive breast carcinoma of no special type (2.6%). A total of 12 mutations were found with the following frequencies: L755S (25.00%), V777L (25.00%), S310Y (16.67%), L869R (16.67%), S310F (8.33%), and D769H (8.33%). Matched tumor samples from six patients identified the same mutations with an 83% concordance rate. In summary, our highly sensitive multiplex digital PCR assays are well suited for plasma‐based monitoring of ERBB2 mutational status in patients with MBC.

Abstract Objective The objective of this study is to develop a novel therapeutic approach for the treatment of ovarian cancer while investigating the role of tumor-infiltrating lymphocytes (TILs) in the context of ovarian cancer therapy. The primary aim is to establish a technical procedure for the isolation of tumor cells, lymphocytes, and dendritic cells (DCs) derived from ovarian cancer tissues or ascites. Subsequently, the focus lies on the generation of dendritic cell-tumor infiltrating lymphocytes (DC-TILs) exhibiting specific cytotoxic capabilities aimed at targeted therapeutic interventions. The cytotoxic impact of DC-TIL interactions on tumor cells was investigated through in vitro experimentation. This research aims to provide fundamental experimental insights for the future clinical advancement of TIL therapy in ovarian cancer. Methods The experimental samples included fresh surgical specimens and ascites specimens procured from three patients (ranging in age from 32 to 75), sourced from the Department of Gynecology at the Third Bethune Hospital of Jilin University. TILs were extracted through in vitro isolation from solid tumor tissues, while primary tumor cells and DCs were obtained from ascites specimens. Tumor-specific antigens derived from patient tumor cells were utilized to stimulate the maturation of DCs. TILs were subsequently co-cultured with antigen-stimulated DC cells. Subsequently, TILs with specific killing effects were obtained, and the cytotoxic impact of DC-TILs on tumor cells was detected in vitro. Results (1) TILs were successfully obtained through expansion from the tumor tissue of a patient diagnosed with ovarian cancer. (2) DCs were successfully induced from ascites cells harvested from patients diagnosed with ovarian cancer. (3) TILs significantly enhanced the cytotoxicity of tumor cells following DC stimulation. Conclusion TILs have the capacity to augment the cytotoxicity directed towards tumor cells following DC stimulation.

Abstract Objective To evaluate the efficacy of sentinel lymph node biopsy (SLNB) in cT1/2N0 minor salivary gland cancer (mSGC) located within the oral cavity. Methods A retrospective analysis was conducted on patients diagnosed with cT1/2N0 oral mSGC, who were categorized into two groups based on neck management approaches. The impact of SLNB versus observation on regional control and overall survival was assessed using a Cox model. Results A total of 177 patients were included in the study, with 53 cases undergoing SLNB. All patients had at least one sentinel lymph node, with the majority having two sentinel lymph nodes. The sentinel lymph nodes were predominantly situated in level I, followed by level II. Four patients had positive sentinel lymph nodes, all of whom had primary tumors in the tongue or the floor of the mouth, and were classified as cT2 stage. This yielded a sensitivity and specificity of 100%, a false negative rate of 0%, and a negative predictive value of 100% for SLNB in predicting occult metastasis. In terms of regional control, SLNB exhibited a reduced hazard ratio of 0.90 (95% confidence interval: 0.64–0.96) compared to observation. However, SLNB did not confer a superior overall survival benefit compared to observation. Conclusion In patients with cT1/2N0 oral mSGC, SLNB proved to be both technically feasible and oncologically safe. When contrasted with observation, SLNB was associated with enhanced regional control, particularly recommending its use for cases of cT2 mSGC arising from the tongue or the floor of the mouth.

Abstract Background The biological significance of cancer-associated fibroblasts (CAFs) in bladder urothelial carcinoma (BUC) warrants further investigation. There is an urgent need to explore the predictive utility of CAF-related genes for prognosis in BUC. Methods The transcriptome and clinical data of 407 BUC patients in The Cancer Genome Atlas (TCGA) database were analyzed and a prognostic model was established. A total of 476 BUC cases from the E-MTAB-4321 database were used for validation. A risk model was constructed utilizing CAF-related genes through LASSO Cox regression, investigating its association with prognosis, gene mutations, immune cell infiltration, and drug sensitivity in BUC. Results We identified five CAF-related genes (EGFL6, NRSN2, SEMA3D, TM4SF1 and TPST1) in both the TCGA and E-MTAB-4321 datasets, and established a prognostic model using LASSO Cox regression. The high-risk group showed a significant correlation with poor survival. Furthermore, the low-risk group exhibited higher tumor mutational burden and lower levels of immune cell infiltration, and this model holds promise for guiding drug selection in BUC patients. Conclusions These findings underscore the pivotal role of CAF-related genes in prognostic prediction for BUC patients. Clinical decision-making and tailored therapeutics stand to benefit from these results, providing a valuable reference for future research endeavors.

Abstract The incidence of patients diagnosed with either breast cancer (BC) or inflammatory bowel disease (IBD) is increasing each year. IBD has been shown to be strongly associated with the development of a variety of solid tumors, but the relationship with breast cancer is not yet definitive. We explored the causative relationship between IBD and BC using a Mendelian randomization (MR) strategy. MR-Egger regression, weighted median (WM), simple median (SM), maximum likelihood (ML), and inverse variance weighting (IVW) methods were among the analytical techniques used in this work. The examination of heterogeneity was conducted by the use of Cochran's Q test and Rucker's Q test. The sensitivity analysis in this study used the IVW and MR-Egger methodologies. The results of our investigation suggested that IBD had a beneficial impact on estrogen receptor-negative (ER-) breast cancer (odds ratio (OR) = 0.92, P = 0.02). The study did not find a significant association between IBD and the risk of developing overall breast cancer (OR = 0.99, P = 0.60), as well as estrogen receptor-positive (ER+) breast cancer (OR = 1.02, P = 0.60) specifically. In addition, our study findings indicated that there was a detrimental association between ER+ breast cancer and IBD as determined using reverse MR analysis (OR = 1.07, P = 0.04). Furthermore, this analysis failed to observe any significant association between overall breast cancer (OR = 1.07, P = 0.07) or ER- breast cancer (OR = 0.99, P = 0.89) and IBD. Our bidirectional MR study yielded a correlation between IBD and some specific hormone receptor status of BC.

Abstract Chimeric antigen receptor (CAR)-T cell therapy demonstrates substantial efficacy in various hematological malignancies. However, its application in solid tumors is still limited. Clinical studies report suboptimal outcomes such as reduced cytotoxicity of CAR-T cells and tumor evasion, underscoring the need to address the challenges of sliding cytotoxicity in CAR-T cells. Despite improvements from fourth and next-generation CAR-T cells, new challenges include systemic toxicity from continuously secreted proteins, low productivity, and elevated costs. Recent research targets genetic modifications to boost killing potential, metabolic interventions to hinder tumor progression, and diverse combination strategies to enhance CAR-T cell therapy. Efforts to reduce the duration and cost of CAR-T cell therapy include developing allogenic and in-vivo approaches, promising significant future advancements. Concurrently, innovative technologies and platforms enhance the potential of CAR-T cell therapy to overcome limitations in treating solid tumors. This review explores strategies to optimize CAR-T cell therapies for solid tumors, focusing on enhancing cytotoxicity and overcoming application restrictions. We summarize recent advances in T cell subset selection, CAR-T structural modifications, infiltration enhancement, genetic and metabolic interventions, production optimization, and the integration of novel technologies, presenting therapeutic approaches that could improve CAR-T cell therapy’s efficacy and applicability in solid tumors.

Abstract Background Breast cancer remains a leading cause of mortality among women worldwide, necessitating innovative prognostic models to enhance treatment strategies. Methods Our study retrospectively enrolled 9,439 breast cancer patients from 12 independent datasets and single-cell data from 12 patients (64,308 cells). Moverover, 30 in-house clinical cohort were collected for validation. We employed a comprehensive approach by combining ten distinct machine learning algorithms across 108 different combinations to scrutinize 88 pre-existing signatures of breast cancer. To affirm the efficacy of our developed model, immunohistochemistry assays were performed. Additionally, we investigated various potential immunotherapeutic and chemotherapeutic interventions. Results This study introduces an Artificial Intelligence-aided Redox Signature (AIARS) as a novel prognostic tool, leveraging machine learning to identify critical redox-related gene signatures in breast cancer. Our results demonstrate that AIARS significantly outperforms existing prognostic models in predicting breast cancer outcomes, offering a robust tool for personalized treatment planning. Validation through immunohistochemistry assays on samples from 30 patients corroborated our results, underscoring the model’s applicability on a wider scale. Furthermore, the analysis revealed that patients with low AIARS expression levels are more responsive to immunotherapy. Conversely, those exhibiting high AIARS were found to be more susceptible to certain chemotherapeutic agents, including vincristine. Conclusions Our study underscores the importance of redox biology in breast cancer prognosis and introduces a powerful machine learning-based tool, the AIARS, for personalized treatment strategies. By providing a more nuanced understanding of the redox landscape in breast cancer, the AIARS paves the way for the development of redox-targeted therapies, promising to enhance patient outcomes significantly. Future work will focus on clinical validation and exploring the mechanistic roles of identified genes in cancer biology.

Abstract Purpose To determine the effects of anti-B cell surface marker CD20 antibody on the occurrence and progression of endometrial cancer to provide insights into clinical treatment in the future. Methods We performed a two-sample Mendelian randomization analysis (MR) to analyze the causal relationship between EC and immune cell markers. The genome-wide association study (GWAS) data of MS4A1 single nucleotide polymorphism encoding gene of CD20 were collected, and a drug target MR analysis was performed to detect the causal relationship between anti-CD20 antibody and the risk of EC. The risk of follicular lymphoma was used as a positive control, and EC was used as the outcome. Results EC exerted an effect on 28 immunophenotypes, predominantly on CD20. CD20 in immunoglobulin D+ CD38− B cells, memory B cells, and unsw memory B cells increased after EC onset. In addition, we detected one immunophenotype that exerted a dangerous effect on EC, i.e., CD3/TD CD4+ (mature stage of the T cell group). Simultaneously, CD20 could be used as both a risk factor and a protective factor for EC (P > 0.05). Anti-CD20 antibodies significantly reduced the risk of follicular lymphoma, including two GWAS pooled datasets. In addition, anti-CD20 antibodies exerted a protective effect on EC in two GWAS pooled datasets (P > 0.05). Conclusion Our study confirms the close relationship between CD20 and EC. Anti-CD20 antibodies may exert a protective effect on EC and reduce the risk of EC morbidity, providing a reference for future clinical diagnosis and treatment. However, further clinical verification of our results is warranted.

Introduction Although a substantial body of research has analyzed the effectiveness of cigarette package warning labels in tobacco control, the very general health warnings messages (HWMs) on cigarette packaging in China have shown limited effectiveness in deterring youth from smoking. Therefore, this study investigates the impact of specific and more detailed warning text messages on Chinese young people’s risk perception of smoking and their intention to quit. Methods We employed a randomized survey experiment to examine the impact of specific text-based warning labels on Chinese young people’s risk perception of smoking and intention to quit. The total effective sample size was 1064 participants. The subjects were divided into three groups: the first group served as the control group, which was shown the existing cigarette package warning labels; the second group was shown cigarette package warning labels related to cardiovascular, digestive, and respiratory diseases; and the third group was shown cigarette package warning labels related to sexual dysfunction. Results The respiratory disease-related warnings significantly increased young people’s awareness of smoking-related respiratory risks (p

Introduction The global rise in e-cigarette use among adolescents is alarming, with associated socioeconomic inequalities posing potential public health risks. This study examined trends in the socioeconomic inequality in e-cigarette use among South Korean adolescents to inform future regulatory directions. Methods Socioeconomic inequalities in e-cigarette use among Korean adolescents were assessed using data from the Korea Youth Risk Behavior Web-based Survey (KYRBS) from 2011 to 2023. The Concentration Index, a well-established method for measuring health inequalities, was employed. Additionally, this study investigated how the smoking behaviors of family members and friends influence socioeconomic inequality in e-cigarette use among Korean adolescents, using a decomposition analysis. Results The Concentration Index values showed a clear, fluctuating downward trend over 13 years, from -0.12 (95% CI: -0.13 – -0.10) in 2011 to -0.24 (95% CI: -0.26 – -0.21) in 2023. Decomposition analysis revealed that smoking among peer groups, including friends and siblings, was the primary contributor to socioeconomic inequality in e-cigarette use, followed by maternal smoking. Conclusions Socioeconomic inequalities in adolescent e-cigarette use in South Korea are widening, particularly among low socioeconomic status groups. The impact of peer groups on socioeconomic inequalities in e-cigarette use among adolescents is concerning.

Abstract Background Small cell lung cancer (SCLC) stands as one of the most lethal malignancies, characterized by a grim diagnosis and prognosis. The emergence of multi-drug resistance poses a significant hurdle to effective therapy. Although previous studies have implicated the long noncoding RNA LYPLAL1-DT in the tumorigenesis of SCLC, the precise role of the highly expressed LYPLAL1-DT in SCLC chemoresistance and the underlying mechanism remain inadequately understood. Methods cDDP-, VP-16- and PTX-resistant SCLC cells lines were established. The viabilities of SCLC cells were assessed by CCK-8 assay in vitro and xenograft tumor formation assay in vivo. Apoptosis was evaluated by FACS, Western blot and JC-1 fluorescence staining, while autophagy was explored via autophagic flux detection under confocal microscopy and autophagic vacuole investigation under transmission electron microscopy (TEM). The functional role and mechanism of LYPLAL1-DT were further investigated by gain- and loss-of-function assays in vitro. Furthermore, the therapeutic efficacy of the combination of venetoclax and HCQ with cDDP, VP-16 or PTX was evaluated by cell line, cell-derived xenograft (CDX) and patient-derived xenograft (PDX) mice model. Results Our findings revealed that LYPLAL1-DT is upregulated in chemoresistant SCLC cell lines. Gain- and loss-of-function assays demonstrated that LYPLAL1-DT impairs sensitivity to cDDP, VP-16, or PTX both in vitro and in vivo. Overexpression of LYPLAL1-DT significantly enhanced autophagy and inhibited apoptosis in SCLC cells. Further analyses, including RIP and RNA pull-down assays, revealed that LYPLAL1-DT promotes the expression of BCL2 by sponging miR-204-5p and is implicated in the assembly of the autophagy-specific complex (BECN1/PtdIns3K complex). Combining venetoclax and HCQ with cDDP, VP-16, or PTX effectively mitigated chemoresistance in SCLC cells and suppressed tumor growth in CDX and PDX models without inducing obvious toxic effects. Conclusions Our findings demonstrate that upregulation of LYPLAL1-DT sequesters apoptosis through the LYPLAL1-DT/miR-204-5p/BCL2 axis and promotes autophagy by facilitating the assembly of the BECN1/PtdIns3K complex, thereby mediating multi-drug resistance of SCLC. The triple combination of venetoclax, HCQ, in conjunction with cDDP, VP-16 or PTX overcomes refractory SCLC, shedding light on a potential therapeutic target for combating SCLC chemoresistance.

Abstract Toxoplasma gondii is a significant zoonotic pathogen of toxoplasmosis in humans and animals. Here a live attenuated Toxoplasma vaccine of WH3 Δrop18 was developed. The results showed that all mice vaccinated with WH3 Δrop18 were able to survive when challenge with various strains of Toxoplasma, including RH (type I), ME49 (type II), WH3 or WH6 (type Chinese 1). No cysts, if few, in the brain of the vaccinated animals were seen after challenge with cyst forming strains of ME49 or WH6. Vaccination with the WH3 Δrop18 triggered a strong immune response, including significantly increased level of the cytokines (IFN-γ, IL-12, TNF-α and IL-10) and the activation of CD4+ and CD8+ T-lymphocytes and long term of specific antibodies against Toxoplasma. Our results strongly indicate that vaccine of WH3 Δrop18 might provide effective immune protection against a wide range strains of Toxoplasma infections and be a promising live attenuated vaccine candidate.

Abstract Diabetic cardiomyopathy (DCM) is a cardiovascular complication of diabetes mellitus with a poor prognosis and is the leading cause of death in diabetic patients. Sleep deficiency is not only recognized as an important risk factor for the development of type 2 DM, but is also associated with increased morbidity and mortality of cardiovascular disease. The underlying role and mechanisms of sleep restriction (SR) in DCM are far from clear. The KK/Upj-Ay mouse model of T2 DM was used as a study subject, and the small animal ultrasound imaging system was used to detect the function of the heart; immunopathological staining was used to clarify the histo-structural pathological alterations of the heart; and TUNEL staining, qPCR, transmission electron microscopy (TEM), and ELISA kits were used to detect apoptosis, oxidative stress, inflammation, and mitochondrial damage, and related molecular alterations. SR led to a significant increase in mortality, cardiac hypertrophy, necrosis, glycogen deposition and fibrosis further deteriorated in DM KK mice. SR increased cardiomyocyte death in KK mice through the Bax/Bcl2 pathway. In addition to this, SR not only exacerbated the inflammatory response, but also aggravated mitochondrial damage and promoted oxidative stress in KK mice through the PRDM16-PGC-1α pathway. Overall, SR exacerbates structural alterations and dysfunction through inflammation, oxidative stress, and apoptosis in DM KK mice, increasing the risk of death. Clinicians and diabetic patients are prompted to pay attention to sleep habits to avoid accelerating the transition of DCM to heart failure and inducing death due to poor sleep habits.

Abstract Background Hepatocellular carcinoma (HCC) is a malignant tumor characterized by a high mortality rate. The occurrence and progression of HCC are linked to oxidative stress. Glyoxalase-1 (GLO1) plays an important role in regulating oxidative stress, yet the underlying mechanism remains unclear. GLO1 may serve as a prognostic biomarker and therapeutic target for HCC. Methods Based on TCGA database hepatocellular carcinoma samples, we conducted a bioinformatics analysis to explore the correlation between GLO1 expression and HCC cell proliferation and viability. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that differentially expressed genes (DEGs) were mainly enriched in the cell cycle pathway. We analyzed the relationships between GLO1 and 24 genes enriched in the cell cycle pathway using a protein-protein interaction (PPI) network. Finally, experimental validation was performed to assess GLO1’s impact on the distribution of cells at different cell cycle stages and on the proliferation and migration of HCC cells. Results Our study demonstrated that GLO1 was overexpressed in HCC tissues and was associated with a poor prognosis. Data analysis indicated that overexpression of GLO1 activated the cell cycle pathway and positively correlated with expression of the majority of key cell cycle genes. Experimental validation showed that GLO1 expression affects the number of HCC cells in G2 and S phases and regulates HCC cell proliferation and migration. Conclusions GLO1 represents a promising therapeutic target for HCC, providing valuable insights into its role in the viability and proliferation of HCC cells.

Abstract Background There is a growing interest in utilizing a combination of brain radiotherapy (RT) and tyrosine kinase inhibitors (TKIs) for patients diagnosed with brain metastases (BM) in epidermal growth factor receptor (EGFR) mutation-positive lung adenocarcinoma (LAC). The current status of this treatment strategy remains a subject of debate. Methods We initiated our study by conducting a comprehensive literature search using the SCI-expanded database of Web of Science Core Collection (WoSCC). We utilized the VOSPviewer software to analyze various aspects of the research, including the year of publication, authorship, keywords, and country.Subsequently, we performed an extensive and systematic literature search on popular online databases. Our primary outcome measures were overall survival (OS) and intracranial progression-free survival (iPFS), both quantified by hazard ratios (HRs). Additionally, for data verification, we included data from patients in non-small cell lung cancer with brain metastasis who underwent therapeutic intervention at the Cancer Prevention and Treatment Center of Sun Yat-sen University and the Radiotherapy Department of Hanzhong Central Hospital between August 2012 and November 2021. Results The bibliometric analysis revealed an increasing trend in research focused on the combination of RT and TKIs for the management of lung cancer brain metastases over the previous decade. Then, nine studies consistent with the research direction were included for meta-analysis. The meta-analysis showed that the OS (HR = 0.81, 95% confidence interval: 0.69–0.94; P = 0.007) and iPFS (HR = 0.71, 95% confidence interval: 0.61–0.82; P

Abstract Purpose Heparan sulfate proteoglycans (HSPGs) are complex molecules found on the cell membrane and within the extracellular matrix, increasingly recognized for their role in tumor progression. This study aimed to investigate the involvement of Heparan sulfate proteoglycan 2 (HSPG2) in the progression of bladder cancer. Methods We identified HSPG2 as a promoter of bladder tumor progression using single-cell RNA sequencing and transcriptome analysis of sequencing data from seven patient samples obtained from the Gene Expression Omnibus (GEO) database (GSE135337). Transcript profiles of 28 normal tissues and 407 bladder tumor tissues were analyzed for HSPG2 expression and survival outcomes using the Sanger tools and cBioPortal databases. HSPG2-overexpressing T24 and Biu-87 cell lines were generated, and cell proliferation and migration were assessed using CCK-8 and Transwell assays. Western blotting and immunostaining were performed to evaluate the activation of Nidogen-1 (NID1)/protein kinase B (AKT) signaling. Mouse models with patient-derived tumor organoids (HSPG2high and HSPG2low) were established to assess anticancer effects. Results Our results demonstrated a marked upregulation of HSPG2 in malignant bladder tumors, which correlated significantly with poor patient prognosis. HSPG2 overexpression consistently enhanced bladder tumor cell proliferation and conferred chemotherapy resistance, as shown in both in vitro and in vivo experiments. Mechanistically, HSPG2 upregulated NID1 expression, leading to the activation of the AKT pro-survival signaling pathway and promoting sustained tumor growth in bladder cancer. Conclusion This study highlights the critical pro-tumor role of HSPG2/NID1/AKT signaling in bladder cancer and suggests its potential as a therapeutic target in clinical treatment.

Abstract In recent years, cell therapy research and commercialization have significantly accelerated, especially after the US FDA approved CAR-T therapy. While cell therapy now leads immuno-oncology in clinical trials, challenges such as redundant R&D, target clustering, and unmet clinical need remain. Since 2017, China has established a dual-track regulatory framework, facilitating rapid growth in its cell therapy pipeline, making it the second largest in the world. Despite this progress, China faces similar global challenges. Our study covers 2,794 registered cell therapy clinical trials in China, including 2,045 for immune cell, 683 for stem cell, and 66 for other somatic cell. It compares cell therapy products approved in China, the US, EU, and Japan, analyzes the evolving clinical trials landscape, and highlights the characteristics of investigator-initiated trials (IITs) and industry-sponsored trials (ISTs) in China. Our findings indicate that despite the high disease burden and unmet clinical needs for solid tumors in China, over 38% of trials between 2021 and 2023 focused on hematologic malignancies with established targets like CD19 and BCMA. Over 90% of trials are IITs, which show notable clinical differences from ISTs. We recommend that Chinese regulators establish specific guidelines to promote clinical-value-driven research. Stricter regulatory standards should also be implemented to minimize redundant R&D. Additionally, a value-based reimbursement system for within-class targeted cell therapy products may further reduce duplicated R&D efforts. Given the prevalence of IITs, specifying requirements for IITs could create a new pathway to accelerate product development and better address unmet clinical needs in China.

Abstract Background Immune checkpoint blockade (ICB) has been improving the patient outcome in multiple cancer types. However, not all patients respond to ICB. Biomarkers are needed for selecting appropriate patients to receive ICB. CD74 is an important chaperone that regulates antigen presentation for immune response. However, the relationship between CD74 expression and ICB response remains elusive. Methods The unified normalized pan-cancer dataset was downloaded from the UCSC database. Wilcoxon Rank Sum Rank Tests were used to analyze the expression differences between normal and tumor samples in each tumor type. Then, the prognostic value of CD74 was determined using univariable Cox proportional hazards regression analysis. The STRING database was utilized to construct the protein-protein interaction (PPI) network of CD74 and the signal pathways were analyzed as well. The correlation of CD74 expression with immune cells and immune regulating genes was investigated in the TIMER database. The TIDE framework was utilized to evaluate the relationship between CD74 expression and the response to immunotherapy. Moreover, the localization of CD74 in the tumor immune microenvironment was verified using multiplex immunohistochemistry. Clinically annotated samples from 38 patients with esophageal cancer treated with neoadjuvant chemotherapy combined with ICB were analyzed for CD74 expression using immunohistochemistry. Results In this study, we investigated the prognostic and predictive value of CD74 in different types of cancer. Compared with normal tissue, the expression of CD74 was higher in tumor tissue in various cancers. High expression of CD74 was associated with improved patient prognosis in the majority of cancers. CD74 and its interacting proteins were mainly enriched in the immune-related pathways. The expression of CD74 was significantly positively correlated with B cells, CD4 T-cells, CD8 T-cells, neutrophils, macrophages and dendritic cells. TIDE analysis showed that tumors with high CD74 expression may have better responses to immunotherapy and improved patient survival. In patients with esophageal cancer who had received ICB, higher intratumoral CD74 expression was associated with improved response to ICB. Conclusions The findings of this study suggest that the high expression of CD74 may be a potential predictive biomarker of response to ICB.

Jun Du,1,&ast; Zijie An,2,&ast; Kun Zhu2 1Department of Oncological Surgery, The First Affiliated Hospital of Bengbu Medical University, Bengbu, People’s Republic of China; 2Department of Orthopaedics, The First Affiliated Hospital of Bengbu Medical University, Bengbu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kun Zhu, Department of Orthopaedics, The First Affiliated Hospital of Bengbu Medical University, Bengbu, People’s Republic of China, Email zk19870128@163.comObjective: To investigate the therapeutic efficacy of totally laparoscopic total gastrectomy (TLTG) versus laparoscopy-assisted total gastrectomy (LATG) in gastric cancer (GC) treatment, as well as their effects on postoperative inflammation and glucose and lipid metabolic status.Methods: Clinical data of 68 individuals with GC who underwent LATG (n=31) and TLTG (n=37) from January 2020 to December 2022 were procured. This included intraoperative blood loss, operative time, incision length, number of lymph nodes dissected, postoperative complication rates, and recovery indicators, such as inflammation, glucose metabolism, and lipid metabolism.Results: The TLTG cohort demonstrated significant advantages in intraoperative blood loss, operative time, and incision length compared to the LATG cohort. Furthermore, TLTG was superior in reducing the incidence of complications. Nevertheless, no substantial variation was observed in the quantity of lymph nodes dissected. Additionally, TLTG showed benefits in postoperative recovery, including better control of the inflammatory response, reduction of complication risks, shorter hospital stay, and alleviation of postoperative pain. TLTG also exhibited a reduced impact on inflammation and demonstrated greater effectiveness in improving postoperative glucose and lipid levels.Conclusion: TLTG surgery is associated with superior clinical outcomes in the treatment of GC compared to LATG, particularly in reducing surgical trauma and accelerating postoperative recovery. Furthermore, TLTG facilitates the resolution of postoperative inflammatory responses and the amelioration of metabolic disorders. The findings from this investigation advocate for the broader adoption of TLTG in the surgical treatment of GC.Keywords: totally laparoscopic total gastrectomy, laparoscopy-assisted total gastrectomy, gastric cancer, inflammatory markers, glucose and lipid metabolism

Abstract Background Neoadjuvant chemoradiotherapy followed by total mesorectal excision is a standard treatment for locally advanced rectal cancer. Mismatch repair-deficient locally advanced rectal cancer (LARC) was highly sensitive to PD-1 blockade. However, most rectal cancers are microsatellite stable (MSS) or mismatch repair-proficient (pMMR) subtypes for which PD-1 blockade is ineffective. Radiation can trigger the activation of CD8 + T cells, further enhancing the responses of MSS/pMMR rectal cancer to PD-1 blockade. Radioimmunotherapy offers a promising therapeutic modality for rectal cancer. Progenitor T exhausted cells are abundant in tumour-draining lymph nodes and play an important role in immunotherapy. Conventional irradiation fields include the mesorectum and regional lymph nodes, which might cause considerable damage to T lymphocytes and radiation-induced fibrosis, ultimately leading to a poor response to immunotherapy and rectal fibrosis. This study investigated whether node-sparing modified short-course irradiation combined with chemotherapy and PD-1 blockade could be effective in patients with MSS/ pMMR LARC. Methods This was a open-label, single-arm, multicentre, prospective phase II trial. 32 LARC patients with MSS/pMMR will receive node-sparing modified short-course radiotherapy (the irradiated planned target volume only included the primary tumour bed but not the tumour-draining lymph nodes, 25 Gy/5f, 5 Gy/f) followed by CAPOX and tislelizumab. CAPOX and tislelizumab will be started two days after the completion of radiotherapy: oxaliplatin 130 mg/m2 intravenous infusion, day 1; capecitabine 1000 mg/m2 oral administration, days 1–14; and tislelizumab 200 mg, intravenous infusion, day 1. There will be four 21-day cycles. TME will be performed at weeks 14–15. We will collect blood, tumour, and lymphoid specimens; perform flow cytometry and in situ multiplexed immunofluorescence detection; and analyse the changes in various lymphocyte subsets. The primary endpoint is the rate of pathological complete response. The organ preservation rate, tumour regression grade, local recurrence rate, disease-free survival, overall survival, adverse effects, and quality of life will also be analysed. Discussion In our research, node-sparing modified radiotherapy combined with immunotherapy probably increased the responsiveness of immunotherapy for MSS/pMMR rectal cancer patients, reduced the occurrence of postoperative rectal fibrosis, and improved survival and quality of life. This is the first clinical trial to utilize a node-sparing radiation strategy combined with chemotherapy and PD-1 blockade in the neoadjuvant treatment of rectal cancer, which may result in a breakthrough in the treatment of MSS/pMMR rectal cancer. Trial registration This study was registered at www.clinicaltrials.gov . Trial registration number: NCT05972655. Date of registration: 31 July 2023.

Abstract Background & aims The benefit of postoperative adjuvant transcatheter arterial chemoembolization (pTACE) for patients with hepatocellular carcinoma (HCC), especially those with Child-Pugh (CP) B, remains controversial. This study aimed to assess the survival benefit of pTACE for HCC patients with CP B. Methods Data from 297 HCC patients with CP B7 or B8 were analyzed, dividing them into groups with and without pTACE (70, 23.6% vs. 227, 76.4%). Propensity score matching (PSM) was used to control for confounding bias, and competing-risk regression was applied to address bias from non-cancer-specific death (NCSD). Results Preliminary findings suggest that pTACE did not increase the incidence of severe complications in HCC patients with CP B7 or B8. Survival analysis indicated that the group receiving pTACE had better overall survival and recurrence-free survival than the group without pTACE after PSM. Furthermore, competitive risk analysis revealed that pTACE was an independent prognostic factor associated with reduced cancer-specific death incidence (subdistribution hazard ratio [SHR] 0.644, 95%CI: 0.378–0.784, P = 0.011) and recurrence (SHR 0.635, 95% CI: 0.379–0.855, P = 0.001). Importantly, pTACE did not increase NCSD. Subgroup analysis corroborated these results. Conclusion Adjuvant TACE demonstrates the potential to significantly enhance the long-term prognosis of HCC patients with CP B7 or B8 following hepatectomy, particularly those with multiple tumors, large tumor size, macrovascular or microvascular invasion, and narrow resection margin. Hence, pTACE should be considered for patients at high risk of recurrence following thorough evaluation.

Abstract There is limited research on the clinicopathological characteristics of combined hepatocellular-cholangiocarcinoma (cHCC-CCA) currently. The aim of this study is to summerize the clinicopathological factors and prognosis of cHCC-CCA, which could help us understand this disease. 72 cases of cHCC-CCA from West China Hospital of Sichuan University were collected. Tissue components were reviewed by pathologists. Immunohistochemistry was used to detect the status of mismatch repair (MMR) and human epidermal growth factor receptor 2 (HER2) in cHCC-CCA, as well as the quantity and distribution of CD3+ T cells and CD8+ T cells. Fluorescence in situ hybridization was used to detect fibroblast growth factor receptor 2 (FGFR2) gene alteration. COX univariate and multivariate analyses were used to evaluate risk factors, and survival curves were plotted. 49 cases were classified as classic type cHCC-CCA and 23 cases as intermediate cell carcinoma. The cut-off value for diagnosing classic type was determined to be ≥ 30% for the cholangiocarcinoma component based on prognostic calculations. All tumors were MMR proficient. The rate of strong HER2 protein expression (3+) was 8.3%, and the frequency of FGFR2 gene alteration was 26.4%. CD3+ T cells and CD8+ T cells were mainly distributed at the tumor margin, and were protective factors for patients with cHCC-CCA. The overall survival of the 72 patients was 18.9 months, with a median survival of 12 months. Tumor size, TNM stage, and serum AFP level were prognostic factors for cHCC-CCA. The proportion of cholangiocarcinoma component reaching the threshold of 30%, may provide a reference for future pathology diagnosis. FGFR2 gene alteration was 26.4%, providing a clue for anti-FGFR2 therapy. However, more data is needed for further verification.

Abstract Background Gallbladder cancer (GBC) is a highly aggressive malignancy, with limited survival profiles after curative surgeries. This study aimed to develop a practical model for predicting the postoperative overall survival (OS) in GBC patients. Methods Patients from three hospitals were included. Two centers (N = 102 and 100) were adopted for model development and internal validation, and the third center (N = 85) was used for external testing. Univariate and stepwise multivariate Cox regression were used for feature selection. A nomogram for 1-, 3-, and 5-year postoperative survival rates was constructed accordingly. Performance assessment included Harrell's concordance index (C-index), receiver operating characteristic (ROC) curves and calibration curves. Kaplan-Meier curves were utilized to evaluate the risk stratification results of the nomogram. Decision curves were used to reflect the net benefit. Results Eight factors, TNM stage, age-adjusted Charlson Comorbidity Index (aCCI), body mass index (BMI), R0 resection, blood platelet count, and serum levels of albumin, CA125, CA199 were incorporated in the nomogram. The time-dependent C-index consistently exceeded 0.70 from 6 months to 5 years, and time-dependent ROC revealed an area under the curve (AUC) of over 75% for 1-, 3-, and 5-year survival. The calibration curves, Kaplan-Meier curves and decision curves also indicated good prognostic performance and clinical benefit, surpassing traditional indicators TNM staging and CA199 levels. The reliability of results was further proved in the independent external testing set. Conclusions The novel nomogram exhibited good prognostic efficacy and robust generalizability in GBC patients, which might be a promising tool for aiding clinical decision-making.

Background and objective: Few studies on endoscopic management of primary obstructive megaureter (POM) in adult patients have been reported. Our objective was to describe our technique and long-term outcomes for endoscopic management of adult POM. Methods: We included 76 adult POM patients undergoing endoscopic management between September 2015 and January 2024. Under endoscopic control, the stricture was dilated to 24–30 Fr while maintaining a balloon pressure of 25–35 atm for 3 min. An additional incision of the stenotic ring using either an electrode or holmium laser was performed in 39 patients. Data for patient characteristics, intraoperative variables, surgical complications, and follow-up results were analyzed. A descriptive statistical analysis was performed. Surgical success was defined as no tubes or stents in the body, stable or improved symptoms and renal function, and the absence of reflux or obstruction during the follow-up period. Key findings and limitations: All procedures were completed without conversion to open or laparoscopic surgery. The median operative time was 45 min (range 16–165) with median estimated blood loss of 2 ml (range 0–150). The median postoperative hospital stay was 3 d (range 1–15). No intraoperative complication occurred. At median postoperative follow-up of 42 mo (range 3–100) the overall success rate was 92.1%. Restenosis of the vesicoureteral junction (Clavien-Dindo grade III) occurred in five patients (6.6%), and high-grade vesicoureteral reflux occurred in one patient (1.3%), all of whom required secondary reconstruction surgery. Conclusions and clinical implications: The results indicate that our endoscopic management for adult POM is safe and effective, with favorable long-term outcomes. This approach could potentially serve as a first-line treatment option for adult POM. Patient summary: Primary obstructive megaureter (POM) occurs when the flow of urine is blocked because of a narrow segment in the tube between the kidney and bladder (ureter), which causes widening of the ureter further up. For our minimally invasive technique, a telescope is inserted through the urethra and bladder to reach the ureter for surgical treatment. Our results show that this is a safe procedure for POM in adults.

Abstract Background tRNA-derived small RNAs (tsRNAs) are newly discovered non-coding RNA, which are generated from tRNAs and are reported to participate in several biological processes in diseases, especially cancer; however, the mechanism of tsRNA involvement in colorectal cancer (CRC) and 5-fluorouracil (5-FU) is still unclear. Methods RNA sequencing was performed to identify differential expression of tsRNAs in CRC tissues. CCK8, colony formation, transwell assays, and tumor sphere assays were used to investigate the role of tsRNA-GlyGCC in 5-FU resistance in CRC. TargetScan and miRanda were used to identify the target genes of tsRNA-GlyGCC. Biotin pull-down, RNA pull-down, luciferase assay, ChIP, and western blotting were used to explore the underlying molecular mechanisms of action of tsRNA-GlyGCC. The MeRIP assay was used to investigate the N(7)-methylguanosine RNA modification of tsRNA-GlyGCC. Results In this study, we uncovered the feature of tsRNAs in human CRC tissues and confirmed a specific 5’ half tRNA, 5’tiRNA-Gly-GCC (tsRNA-GlyGCC), which is upregulated in CRC tissues and modulated by METTL1-mediated N(7)-methylguanosine tRNA modification. In vitro and in vivo experiments revealed the oncogenic role of tsRNA-GlyGCC in 5-FU drug resistance in CRC. Remarkably, our results showed that tsRNA-GlyGCC modulated the JAK1/STAT6 signaling pathway by targeting SPIB. Poly (β-amino esters) were synthesized to assist the delivery of 5-FU and tsRNA-GlyGCC inhibitor, which effectively inhibited tumor growth and enhanced CRC sensitive to 5-FU without obvious adverse effects in subcutaneous tumor. Conclusions Our study revealed a specific tsRNA-GlyGCC-engaged pathway in CRC progression. Targeting tsRNA-GlyGCC in combination with 5-FU may provide a promising nanotherapeutic strategy for the treatment of 5-FU-resistance CRC. Graphical Abstract

Abstract Circular RNA (circRNA) is thought to mediate the occurrence and development of human cancer and usually acts as a tiny RNA (miRNA) sponge to regulate downstream gene expression. However, it is not clear whether and how circACVR2A (hsa_circ_0001073) is involved in the progression of HCC. The purpose of this study is to clarify the potential role and molecular mechanism of circACVR2A in regulating the progression of hepatocellular carcinoma cells (HCC). The abundance of related proteins in circACVR2A, microRNA (miR511-5p) and PI3K-Akt signaling pathway was determined by quantitative reverse transcriptase polymerase chain reaction (RT-PCR) or Western blotting. Cell viability, invasion and apoptosis were analyzed by CCK-8, Transwell analysis and Tunel staining, respectively. The interaction between circACVR2A and microRNA was evaluated by double luciferase reporter gene assay. The results showed that circACVR2A was highly expressed in hepatocellular carcinoma cell lines. Our in vivo and in vitro data showed that circACVR2A promoted the proliferation, migration and invasion of HCC. In terms of mechanism, we found that circACVR2A can directly interact with miR511-5p and act as a miRNA sponge to regulate the expression of related proteins in PI3K-Akt signaling pathway. In HCC, circACVR2A can mediate miR-511-5p/mRNA network to activate PI3K signal pathway. This shows that the molecular regulatory network with circACVR2A as the core is a new potential target for diagnosis and treatment of hepatocellular carcinoma.

Abstract Background and purpose Various deep learning auto-segmentation (DLAS) models have been proposed, some of which have been commercialized. However, the issue of performance degradation is notable when pretrained models are deployed in the clinic. This study aims to enhance precision of a popular commercial DLAS product in rectal cancer radiotherapy by localized fine-tuning, addressing challenges in practicality and generalizability in real-world clinical settings. Materials and methods A total of 120 Stage II/III mid-low rectal cancer patients were retrospectively enrolled and divided into three datasets: training (n = 60), external validation (ExVal, n = 30), and generalizability evaluation (GenEva, n = 30) datasets respectively. The patients in the training and ExVal dataset were acquired on the same CT simulator, while those in GenEva were on a different CT simulator. The commercial DLAS software was first localized fine-tuned (LFT) for clinical target volume (CTV) and organs-at-risk (OAR) using the training data, and then validated on ExVal and GenEva respectively. Performance evaluation involved comparing the LFT model with the vendor-provided pretrained model (VPM) against ground truth contours, using metrics like Dice similarity coefficient (DSC), 95th Hausdorff distance (95HD), sensitivity and specificity. Results LFT significantly improved CTV delineation accuracy (p

PURPOSEResponse assessment of classical Hodgkin lymphoma (cHL) with positron emission tomography-computerized tomography (PET-CT) is standard of care in well-resourced settings but unavailable in most African countries. We aimed to investigate correlations between changes in PET-CT findings at interim analysis with changes in blood test results in pediatric patients with cHL in 17 South African centers.METHODSChanges in ferritin, lactate dehydrogenase (LDH), erythrocyte sedimentation rate (ESR), albumin, total white cell count (TWC), absolute lymphocyte count (ALC), and absolute eosinophil count were compared with PET-CT Deauville scores (DS) after two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine in 84 pediatric patients with cHL. DS 1-3 denoted rapid early response (RER) while DS 4-5 denoted slow early response (SER). Missing values were imputed using the k-nearest neighbor algorithm. Baseline and follow-up blood test values were combined into a single difference variable. Data were split into training and testing sets for analysis using Python scikit-learn 1.2.2 with logistic regression, random forests, naïve Bayes, and support vector machine classifiers.RESULTSRandom forest analysis achieved the best validated test accuracy of 73% when predicting RER or SER from blood samples. When applied to the full data set, the optimal model had a predictive accuracy of 80% and a receiver operating characteristic AUC of 89%. The most predictive variable was the differences in ALC, contributing 21% to the model. Differences in ferritin, LDH, and TWC contributed 15%-16%. Differences in ESR, hemoglobin, and albumin contributed 11%-12%.CONCLUSIONChanges in low-cost, widely available blood tests may predict chemosensitivity for pediatric cHL without access to PET-CT, identifying patients who may not require radiotherapy. Changes in these nonspecific blood tests should be assessed in combination with clinical findings and available imaging to avoid undertreatment.

Introduction Previous studies have suggested that adolescents may smoke cigarettes to control weight, but relevant research is scarce in Chinese youth. This study was conducted to examine the associations of weight control related behaviors with cigarette smoking in Chinese students. Methods This was a secondary analysis of data for 24835 middle and high school students drawn from the 2022 Zhejiang Youth Risk Behavior Survey of China which collected self-reported information of cigarette smoking, weight control strategies and other health-related behaviors. Multivariable logistic regression models were used to estimate the adjusted odds ratios (AORs) with 95% confidence intervals (CIs) for the study associations. Results Overall, there were 998 (4.02%) current cigarette smokers in this wave of the Zhejiang YRBS (2022). Neither trying to control weight nor healthy weight control behavior of exercising was associated with current cigarette smoking (AOR=1.15; 95% CI: 0.97–1.37 and AOR=1.01; 95% CI: 0.85–1.20, respectively). Meanwhile, unhealthy weight control behaviors of taking laxatives (AOR=1.52; 95% CI: 1.03–2.26), taking diet pills (AOR=1.82; 95% CI: 1.26–2.62), dieting (AOR=1.24; 95% CI: 1.04–1.49), and fasting (AOR=1.81; 95% CI: 1.40–2.34) were significantly associated with increased odds of current cigarette smoking. Conclusions Screening and developing interventions for unhealthy weight control behaviors should be considered as part of smoking prevention programs among adolescents.

Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related deaths worldwide. Dendritic cells (DCs) constitute a heterogeneous group of antigen-presenting cells that are important for initiating and regulating both innate and adaptive immune responses. As a crucial component of the immune system, DCs have a pivotal role in the pathogenesis and clinical treatment of CRC. DCs cross-present tumor-related antigens to activate T cells and trigger an antitumor immune response. However, the antitumor immune function of DCs is impaired and immune tolerance is promoted due to the presence of the tumor microenvironment. This review systematically elucidates the specific characteristics and functions of different DC subsets, as well as the role that DCs play in the immune response and tolerance within the CRC microenvironment. Moreover, how DCs contribute to the progression of CRC and potential therapies to enhance antitumor immunity on the basis of existing data are also discussed, which will provide new perspectives and approaches for immunotherapy in patients with CRC.

Abstract Prostate cancer (PCa) and breast cancer (BC) present formidable challenges in global cancer-related mortality, necessitating effective management strategies. The present study explores non-canonical Wnt signaling in PCa and BC, aiming to identify biomarkers and assess their clinical and therapeutic implications. Co-expression analyses reveal distinct gene patterns, with five overlapping genes (SULF1, ALG3, IL16, PLXNA2 and RASGFR2) exhibiting divergent expression in both cancers. Clinical relevance investigations demonstrate correlations with TNM stages and biochemical recurrence. Drug correlation analyses unveil potential therapeutic avenues, indicating that Wnt5a and ROR2 expressions are related to MEK inhibitor sensitivity in cancers. Meanwhile, further correlation analyses were conducted between drugs and the other novel non-canonical WNT genes (ALG3, IL16, SULF1, PLXNA2, and RASGRF2). Our findings contribute to understanding non-canonical Wnt signaling, offering insights into cancer progression and potential personalized treatment approaches.

Abstract Background Esophageal squamous cell carcinoma (ESCC) stands as a significant global health challenge, distinguished by its aggressive progression from the esophageal epithelium. Central to this malignancy is sphingolipid metabolism, a critical pathway that governs key cellular processes, including apoptosis and immune regulation, thereby influencing tumor behavior. The advent of single-cell and transcriptome sequencing technologies has catalyzed significant advancements in oncology research, offering unprecedented insights into the molecular underpinnings of cancer. Methods We explored sphingolipid metabolism-related genes in ESCC using scRNA-seq data from GEO and transcriptome data from TCGA. We assessed 97 genes in epithelial cells with AUCell, UCell, and singscore algorithms, followed by bulk RNA-seq and differential analysis to identify prognosis-related genes. Immune infiltration and potential immunotherapeutic strategies were also investigated, and tumor gene mutations and drug treatment strategies were analyzed. Result Our study identified distinct gene expression patterns, highlighting ARSD, CTSA, DEGS1, and PPTQ's roles in later cellular stages. We identified seven independent prognostic genes and created a precise nomogram for prognosis. Conclusion This study integrates single-cell and transcriptomic data to provide a reliable prognostic model associated with sphingolipid metabolism and to inform immunotherapy and pharmacotherapy for ESCC at the genetic level. The findings have significant implications for precision therapy in esophageal cancer.

Fangqian Du,1,&ast; Yuwei Xie,1,&ast; Shengze Wu,1 Mengling Ji,2 Bingzi Dong,3 Chengzhan Zhu1 1Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China; 2Department of Surgery, Institute of Biomedical Sciences, Tokushima University, Tokushima, Japan; 3Department of Endocrinology and Metabolism, The Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chengzhan Zhu, Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China, Tel +86 0532-82919552, Fax +86 0532-82911885, Email zhuchengz@qduhospital.cn Bingzi Dong, Department of Endocrinology and Metabolism, The Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China, Tel/Fax +86-82911383, Email dongbingzi@hotmail.comAbstract: Hepatobiliary and pancreatic diseases are becoming increasingly common worldwide and associated cancers are prone to recurrence and metastasis. For a more accurate treatment, new therapeutic strategies are urgently needed. The claudins (CLDN) family comprises a class of membrane proteins that are the main components of tight junctions, and are essential for forming intercellular barriers and maintaining cellular polarity. In mammals, the claudin family contains at least 27 transmembrane proteins and plays a major role in mediating cell adhesion and paracellular permeability. Multiple claudin proteins are altered in various cancers, including gastric cancer (GC), esophageal cancer (EC), hepatocellular carcinoma (HCC), pancreatic cancer (PC), colorectal cancer (CRC) and breast cancer (BC). An increasing number of studies have shown that claudins are closely associated with the occurrence and development of hepatobiliary and pancreatic diseases. Interestingly, claudin proteins exhibit different effects on cancer progression in different tumor tissues, including tumor suppression and promotion. In addition, various claudin proteins are currently being studied as potential diagnostic and therapeutic targets, including claudin-3, claudin-4, claudin-18.2, etc. In this article, the functional phenotype, molecular mechanism, and targeted application of the claudin family in hepatobiliary and pancreatic diseases are reviewed, with an emphasis on claudin-1, claudin-4, claudin-7 and claudin-18.2, and the current situation and future prospects are proposed.Keywords: claudins, hepatocellular carcinoma, cholangiocarcinoma, pancreatic cancer, targeted therapy

Abstract DP303c is a HER2-targeted ADC with a cleavable linker-MMAE payload. Previous in vitro studies demonstrated that DP303c showed similar or better antitumor activity than T-DM1 in xenograft models. This was a multicenter, dose escalation and dose expansion phase 1 study in China. Eligible patients were 18-75 years old with HER2-positive advanced solid tumors who were unable to benefit from standard therapy. DP303c was administered intravenously every 3 weeks, with accelerated titration at lower dose of 0.5 mg/kg and 3 + 3 design with dose levels of 1.0, 2.0, 3.0 or 4.0 mg/kg at dose escalation part, followed by the selected dose level at dose expansion part. The primary endpoints were safety and tolerability, as well as identification of recommended phase 2 dose. As of Feb 28, 2023, 94 patients were enrolled and received DP303c (dose escalation: n = 22; dose expansion: n = 72), of whom 68 patients had breast cancer. One dose limiting toxicity (Grade 3 eye pain) was observed at 4.0 mg/kg dose, and the maximum tolerated dose was not reached. The most common treatment-related adverse events at grade 3 or higher were blurred vison (16.0%), dry eye (6.4%), and peripheral neuropathy (5.3%). No treatment-related death occurred. Overall, among 91 efficacy evaluable patients, 39 patients (42.9%) achieved an objective response. Disease control was observed in 62 patients (68.1%). In 66 efficacy evaluable patients with breast cancer, 34 patients achieved an objective response (51.5%). Disease control was achieved in 51 patients (77.3%). Median PFS was 6.4 months. On a molar basis, DP303c Cmax at 3.0 mg/kg doses was 132-folder higher than that for free MMAE. DP303c demonstrated promising anti-tumor activity with acceptable safety in patients with pre-treated advanced HER2 positive solid tumors, especially in breast cancer. Based on safety and efficacy results, 3.0 mg/kg Q3W was determined as recommended phase 2 dose for DP303c. (Trial registration: ClinicalTrials.gov Identifier: NCT04146610).

Abstract Background Breast cancer (BRCA) remains to be among the main causes of cancer-associated mortality in women globally. HGH1 homolog (HGH1) has been reported to be associated with tumor immunity. However, the function of HGH1 in BRCA remains unclear. Therefore, the present study examined the potential role of HGH1 in BRCA. Methods The Cancer Genome Atlas (TCGA) databases and Gene Expression Omnibus (GEO) were used to obtain RNA-seq data for BRCA. A protein localization of HGH1 was determined by using the Human Protein Atlas (HPA), and immunohistochemistry (IHC) staining revealed an upregulation in the expression of HGH1 in clinical BRCA tissues. Xenograft mice were used to test tumor growth and HGH1 expression in breast cancer cells. The protein interaction information of HGH1 was analyzed using the GeneMANIA website. Based on univariate Cox regression and Kaplan-Meier methods, we evaluated the role of HGH1 in BRCA prognosis. HGH1-related differentially expressed genes were analyzed using GO, KEGG, and GSEA. We also examined the relationship between HGH1 expression, immune checkpoints, and immune infiltration. CCK-8, EdU, and colony formation assays were used to measure cell proliferation, and western blot analysis was used to evaluate HGH1’s role in BRCA. Results IHC results showed that the expression of HGH1 was significantly upregulated in BRCA tissues compared to normal tissues. High levels of HGH1 expression was associated with worse clinical features and a worse prognosis. HGH1 expression was an independent predictor of BRCA outcomes in both univariate and multivariate analyses. Functionally, western blot analysis showed that HGH1 is implicated in cell cycle. As well, knocking down HGH1 significantly reduced BRCA cells’ proliferative abilities. Crucially, HGH1 expression levels were positively correlated with Th2 cell infiltration and negatively correlated with Tcm cell infiltration. Conclusion Biomarkers such as HGH1 can reliably predict prognosis in BRCA patients.