A Novel m7G-Related Genes-Based Signature with Prognostic Value and Predictive Ability to Select Patients Responsive to Personalized Treatment Strategies in Bladder Cancer

SIMPLE SUMMARY: Although N7-methylguanosine (m7G) modification serves as a tumor promoter in bladder cancer (BLCA), the comprehensive role of m7G-related characterization in BLCA remains unclear. In this study, we integrated three cohorts consisting of 760 BLCA patients and used a consensus unsupervised clustering method to classify the BLCA patients into different clusters based on 18 m7G-related genes. Next, we identified some candidate proteins via various approaches to reveal the potential mechanism among these m7G-related clusters. Finally, we developed a novel scoring system depending on the GSVA algorithm. The constructed m7G-related signature can accurately be used for risk stratification. Most importantly, our signature can effectively predict patients’ response to immunotherapy and some targeted chemotherapeutic drugs. We believe our research can guide more clinical therapeutic strategies, improving the survival of BLCA patients in the future. ABSTRACT: Although N7-methylguanosine (m7G) modification serves as a tumor promoter in bladder cancer (BLCA), the comprehensive role of m7G-related characterization in BLCA remains unclear. In this study, we systematically evaluated the m7G-related clusters of 760 BLCA patients through consensus unsupervised clustering analysis. Next, we investigated the underlying m7G-related genes among these m7G-related clusters. Univariate Cox and LASSO regressions were used for screening out prognostic genes and for reducing the dimension, respectively. Finally, we developed a novel m7G-related scoring system via the GSVA algorithm. The correlation between tumor microenvironment, prediction of personalized therapies and this m7G-related signature was gradually revealed. We first identified three m7G-related clusters and 1108 differentially expressed genes relevant to the three clusters. Based on the profile of 1108 genes, we divided BLCA patients into two clusters, which were quantified by our established m7G-related scoring system. Patients with higher m7G-related scores tended to have a better OS and more chances to benefit from immunotherapy. A significantly negative connection between sensitivity to classic chemotherapeutic drugs and m7G-related signature was uncovered. In summary, our data show that m7G-related characterization of BLCA patients can be of value for prognostic stratification and for patient-oriented therapeutic options, designing personalized treatment strategies in the preclinical setting.