| Background:In recent years,precision medicine has developed rapidly in the diagnosis and treatment of tumor and other major diseases.As a common tumor,the incidence of bladder cancer continues to rise,and the survival rate needs to be further improved.Significant gender differences in bladder cancer suggest that it is necessary to treat male and female patients differently in precision medicine,but the molecular mechanism of gender differences in bladder cancer is not clear at present.This study attempts to identify the main molecular influencing factors of gender differences in bladder cancer,so as to provide theoretical help for improving the differential treatment of male and female patients.Objective:This paper intended to screen out genes with gender bias in bladder cancer,and characterize the changes of these genes at different omics levels,and further reveal the roles of these gene and their involving molecular pathways played in tumor and the impact on prognosis,through analyzing a variety of omics sequencing data of bladder cancer.Methods:In this study,multiple omics sequencing data of 436 bladder cancer samples from TCGA were finely grouped to search for sexdifferential genes and molecular pathways.Firstly,case samples were grouped from different perspectives,including normal group,tumor group,female group and male group.Secondly,autosomes and sex chromosomes were separated in different omics of each group for differential expression analysis and enrichment analysis.Thirdly,combined with comprehensive clinical and pathological data,prognostic analyses were conducted to explore gender bias genes in bladder cancer.Finally,in order to reveal the main characteristics of those key genes or gene families in bladder cancer,comprehensive and systematic analyses were performed.Results:From the perspective of chromosome,we found that the gender difference of bladder cancer was mainly reflected in the X chromosome,and no significant gender difference molecules were identified on the corresponding autosomal.There were significant sex differences in DNA methylation and mRNA analysis on X chromosome,especially at the DNA methylation level,but no significant sex differences were identified in miRNA.The genes corresponding to sex difference methylation sites in both normal and tumor samples were significantly enriched in ww domain binding pathway is composed of the TCEALs gene family.At the level of mRNA,no significant sex differential genes were found in normal samples,but sex differential genes were detected in tumor samples,and these sex differential genes were significantly enriched in histone demethylase activity and translation initiation factor activity pathway,respectively,affected by KDM5C/KDM6A and EIF1AX/EIF2S3.The results of the difference analysis between tumor and normal samples showed that TCEALs was significantly correlated with the development of bladder cancer,which fully indicated that the TCEALs gene family was related to the gender difference of bladder cancer.In further analysis,we systematically revealed that the KDMs gene family is characterized by high mutation complementarity,overexpression and negative correlation with hypomethylation in bladder cancer,and is closely related to the prognosis,immune infiltration and drug sensitivity of bladder cancer.Conclusion and significance:This study systematically examined the gender differences on omics level in bladder cancer by using a detailed grouping comparative analysis strategy,and identified the TCEALs gene family and their significant impact on gender differences in bladder cancer.The research results highlight the impact of X-linked tumor suppressor genes on gender differences in tumors,which has important theoretical value in helping to understand the occurrence and development of bladder cancer,as well as gender differentiated prevention and treatment. |
