Integrative multi-omics study identifies sex-specific molecular signatures and immune modulation in bladder cancer

作者：Yizhou Wang, Priyanka Bhandary, Kevin Griffin, Jason H. Moore, Xue Li, Zhiping Paul Wang · 发表于：Frontiers in Bioinformatics · 年份：2025 · DOI：10.3389/fbinf.2025.1575790 · 被引用次数：5 · 研究领域：Bladder and Urothelial Cancer Treatments、Ferroptosis and cancer prognosis、Urinary and Genital Oncology Studies

Introduction: Bladder cancer shows distinct sex-related patterns, with male patients experiencing significantly higher incidence and female patients facing poorer survival outcomes. This study aimed to investigate the biological mechanisms underlying these differences using integrative multi-omics analysis. Methods: We analyzed bladder cancer data from TCGA and GTEx, including genomic mutations, gene expression profiles, and clinical information. We performed protein-protein interaction analysis, pathway enrichment, survival analysis, and immune cell correlation. Results: We identified androgen receptor (AR)-related pathways as uniquely enriched in male-specific hub genes, while the Wnt signaling pathway was enriched in female-specific hub genes. In total, 14 male-specific hub genes showed significant sex-biased survival associations, including known markers-DLGAP5, SOX2, LAMA2, and COL5A2-and novel ones such as ERCC5, NID1, ANK2, and others. For females, three hub genes-RAD51C, COL22A1, and COL5A2-were identified as female-specific with survival associations. Additionally, four male-specific hub genes-DAXX, IKBKB, PDGFRA, and PPARG-were immune-related and showed sex-differential correlations with immune cell infiltration, with three of them associated with AR signaling regulation. Discussion: These findings provide new insights into the molecular basis of sex differences in bladder cancer and could pave the way for more personalized and effective therapeutic strategies tailo...