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Cervical cancer remains the leading cause of cancer death in 36 countries, and high-risk human papillomavirus types are responsible for most cases. Identifying strategies to make treatment more targeted and effective has become a priority. This study aims to validate a set of differentially expressed genes previously identified in cervical cancer stem cells as predictive biomarkers for response to chemoradiotherapy using minimally invasive samples. Additionally, it aims to elucidate the relationship between high-risk human papillomavirus infection and cervical cancer patients' response to treatment. Gene expression for three differentially expressed genes (COPZ1, ILF2, and SNX2) was evaluated from 20 cervical cancer patients' cervical cytology brushes. Unmapped reads from the same transcriptome were used to evaluate the presence of human papillomavirus in tumor tissue through qualitative screening of 13 high-risk human papillomavirus types. Our study did not clarify the relationship between high-risk human papillomavirus infection and the treatment response. However, we found downregulation of COPZ1 in patients who responded to treatment compared to non-responders, and ILF2 in patients with more advanced tumor stages. This suggests that COPZ1 and ILF2 expressions are potential cervical cancer prognostic biomarkers that can be assessed using samples commonly used in clinical practice.

Background: Queiroz et al. showed that the application of cluster methodology for classifying gastric cancer is suitable and efficient within a Brazilian cohort, which is known for its population heterogeneity. The study highlighted the potential utilization of this method within public health services due to its low-cost, presenting a viable means to improve the diagnosis and prognosis of gastric cancer., Background: Our Brazilian cohort with gastric cancer has a distinct distribution between mutated and normal p53., Background: New genetic marker-based classifications improve gastric cancer diagnosis accuracy., Background: Machine learning integration enhances predictive value in gastric cancer diagnosis., Background: Molecular biomarkers complement clinical decisions, advancing personalized medicine., Objective: Gastric adenocarcinoma remains an aggressive disease with a poor prognosis, as evidenced by a 5-year survival rate of approximately 31%. The histological classifications already proposed do not accurately reflect the high biological heterogeneity of this neoplasm, particularly in diverse populations, and new classification systems using genetic markers have recently been proposed. Following these newly proposed models, we aimed to assess the cluster distribution in a Brazilian cohort. Furthermore, we evaluated whether the inclusion of other clinical and histological parameters could enhance the predictive value., Methods: We used a previously described four-immunohistochemistry/EBER-ISH marker to classify a cohort of 30 Brazilian patients with gastric adenocarcinoma into five different clusters and compared the distribution with other genetically diverse populations. Furthermore, we used artificial intelligence methods to evaluate whether other clinical and pathological parameters could improve the results of the methodology., Results: Disclosing the genetic variability between populations, we observed a more balanced distribution of the aberrant/normal p53 ratio (0.6) between patients negative for the other markers tested, unlike previous studies with Asian and North American populations. In addition, decision tree analysis reinforced the efficiency of these new classifications, as the stratification accuracy was not altered with or without additional data., Conclusion: Our study underscores the importance of local research in characterizing diverse populations and highlights the complementary role of molecular biomarkers in personalized medicine for gastric adenocarcinoma, enhancing diagnostic accuracy and potentially improving survival rates.

Cervical cancer (CC) poses a significant burden on individuals in developing regions, exhibiting heterogeneous responses to standard chemoradiation therapy, and contributing to substantial mortality rates. Unraveling host immune dynamics holds promise for innovative therapies and discovery of clinically relevant biomarkers. We studied prospectively locally advanced CC patients pre-treatment, stratifying them as responders (R) or non-responders (NR). R patients had increased tumor-infiltrating lymphocytes (TILs), while NR patients showed elevated PD-1 scores, CD8+ and PD-L2+ TILs, and PD-L1 immune reactivity. NR patients exhibited higher systemic soluble mediators correlating with TIL immune markers. R patients demonstrated functional polarization of CD4 T cells (Th1, Th2, Th17, and Treg), while CD8+ T cells and CD68+ macrophages predominated in the NR group. Receiver operating characteristic analysis identified potential CC response predictors, including PD-L1-immunoreactive (IR) area, PD-L2, CD8, FGF-basic, IL-7, IL-8, IL-12p40, IL-15, and TNF-alpha. Dysfunctional TILs and imbalanced immune mediators contribute to therapeutic insufficiency, shedding light on local and systemic immune interplay. Our study informs immunological signatures for treatment prediction and CC prognosis., (© 2023. The Author(s).)

Objective: To investigate the expression of human papillomavirus (HPV), p16, p53, and p63 in non-schistosomiasis-related squamous cell carcinoma of the bladder and to develop an accurate and automated tool to predict histological classification based on clinicopathological features., Methods: Twenty-eight patients with primary bladder pure squamous cell carcinoma who underwent cystectomy or transurethral resection of bladder tumor (TURBT) for bladder cancer between January 2011 and July 2017 were evaluated. Clinical data and follow-up information were obtained from medical records. Formalin-fixed, paraffin-embedded surgical specimens were used for immunohistochemical staining for p16, p53, and p63. Human papillomavirus detection was evaluated by PCR. Statistical analysis was performed, and statistical significance was set at p<0.05. Finally, decision trees were built to classify patients' prognostic features. Leave-one-out cross-validation was used to test the generalizability of the model., Results: Neither direct HPV detection nor its indirect marker (p16 protein) was identified in most cases. The absence of p16 was correlated with less aggressive histological grading (p=0.040). The positive p16 staining detection found only in pT1 and pT2 cases in our sample suggests a possible role for this tumor suppressor protein in the initial stages of bladder squamous cell carcinoma. The decision trees constructed described the relationship between clinical features, such as hematuria/dysuria, the level of tumor invasion, HPV status, lymphovascular invasion, gender, age, compromised lymph nodes, and tumor degree differentiation, with high classification accuracy., Conclusion: The algorithm classifier approach established decision pathways for semi-automatic tumor histological classification, laying the foundation for tailored semi-automated decision support systems for pathologists.

Cervical cancer (CC) represents a major global health issue, particularly impacting women from resource constrained regions worldwide. Treatment refractoriness to standard chemoradiotheraphy has identified cancer stem cells as critical coordinators behind the biological mechanisms of resistance, contributing to CC recurrence. In this work, we evaluated differential gene expression in cervical cancer stem-like cells (CCSC) as biomarkers related to intrinsic chemoradioresistance in CC. A total of 31 patients with locally advanced CC and referred to Mário Penna Institute (Belo Horizonte, Brazil) from August 2017 to May 2018 were recruited for the study. Fluorescence-activated cell sorting was used to enrich CD34+/CD45- CCSC from tumor biopsies. Transcriptome was performed using ultra-low input RNA sequencing and differentially expressed genes (DEGs) using Log2 fold differences and adjusted p-value < 0.05 were determined. The analysis returned 1050 DEGs when comparing the Non-Responder (NR) (n=10) and Responder (R) (n=21) groups to chemoradiotherapy. These included a wide-ranging pattern of underexpressed coding genes in the NR vs. R patients and a panel of lncRNAs and miRNAs with implications for CC tumorigenesis. A panel of biomarkers was selected using the rank-based AUC (Area Under the ROC Curve) and pAUC (partial AUC) measurements for diagnostic sensitivity and specificity. Genes overlapping between the 21 highest AUC and pAUC loci revealed seven genes with a strong capacity for identifying NR vs. R patients ( ILF2, RBM22P2, ACO16722.1, AL360175.1 and AC092354.1 ), of which four also returned significant survival Hazard Ratios. This study identifies DEG signatures that provide potential biomarkers in CC prognosis and treatment outcome, as well as identifies potential alternative targets for cancer therapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zuccherato, Machado, Magalhães, Martins, Campos, Braga, Teixeira-Carvalho, Martins-Filho, Franco, Paula, da Silva, Drummond, Gollob and Salles.)

Purpose: Penile cancer (PC) is a rare neoplasm with an aggressive behavior and variable prognosis. Lymph node (LN) involvement and pathological features of the primary lesion have been proven to be the most important survival factors. Positron emission tomography/computed tomography with fluorodeoxyglucose labelled with fluorine-18 ( 18 F-FDG PET/CT) provides information on tumor staging and works as a prognostic factor, with promising results in other carcinomas. The aim of the present study is to evaluate PET/CT as a prognostic factor in PC., Methods: Fifty-five patients (mean age 56.6 y) diagnosed with penile squamous cell carcinoma were prospectively evaluated from 2012 to 2014. All subjects underwent 18 F-FDG PET/CT before treatment and were regularly followed after surgery., Results: Out of the 53 patients selected, 17 (32.1%) had localized disease (cT1-2) and 24 (45.3%) had palpable nodes (cN+). Partial penile amputation was performed in 38 patients (71.7%) and inguinal lymphadenectomy (LND) in 30 (56.6%). From the LND group, 16 (53.3%) presented with positive neoplastic cells (pN+). Patients with more aggressive disease had a significantly (p = 0.019) higher 18 F-FDG tumor uptake (pSUV max ), while inguinal LN uptake (nSUV max ) was able to recognize metastatic LN (p = 0.039). Some pathological prognostic features, when presented, have shown significant changes in pSUV max values. Receiver operating characteristic (ROC) curves were performed and specific cutoff values of pSUV max were evaluated to determine sensitivity and specificity. Regarding regional LNs, PET/CT presented a 76.2% accuracy in cN+ patients. After a 39-month follow up, pSUV max of 16.6 (p = 0.0001) and nSUV max of 6.5 (p = 0.019) were established as the ideal values to predict cancer-specific survival. The multivariate analysis confirmed nSUV max as a predictor for LN metastasis (p = 0.043) and pSUV max as a mean to estimate survival rate (p = 0.05)., Conclusion: This study showed promising results on the use of 18 F-FDG PET/CT as a prognostic tool for PC, using specific cutoff values of pSUV max and nSUV max .