ORIGINAL RESEARCH article
Front. Bioinform.
Sec. Integrative Bioinformatics
Volume 5 - 2025 | doi: 10.3389/fbinf.2025.1575790
Integrative Multi-Omics Study Identifies Sex-Specific Molecular Signatures and Immune Modulation in Bladder Cancer
Provisionally accepted
- Cedars Sinai Medical Center, Los Angeles, United States
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Bladder cancer shows distinct sex-related patterns, with male patients experiencing significantly higher incidence and female patients facing poorer survival outcomes. In this study, we aimed to address the lack of understanding of the biological mechanisms responsible for this sex-based divergence through an integrative analysis using bladder cancer data from TCGA and GTEx. We analyzed multiple data types, including genomic mutation, gene expression profiles, and clinical information. We conducted an in-depth study of protein-protein interactions, pathway analysis, survival analysis, and immune cell correlations. Notably, we identified androgen receptor (AR) related pathways as uniquely enriched in male-specific hub genes, while the Wnt signaling pathway as uniquely enriched in female hub genes. Additionally, we identified 14 hub genes with significant sex-biased survival rates, including previously known markers (DLGAP5, SOX2, LAMA2, and COL5A2), as well as novel male-specific markers ERCC5, NID1, and ANK2, and female-specific RAD51C, COL22A1 and COL5A2. Furthermore, we identified four male-specific hub genes-DAXX, IKBKB, PDGFRA, and PPARG-that overlapped with immune-related genes and demonstrated differential correlations with immune cells between males and females. Specifically, DAXX, IKBKB and PPARG were functionally associated with AR signaling regulation, suggesting a potential malespecific mechanism of immune modulation. 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 interventions tailored to male and female patients.
Keywords: Bladder cancer, TCGA, sex dimorphism, Wnt Signaling Pathway, AR signaling pathway, immune filtration, survival analysis, integrative analysis
Received: 12 Feb 2025; Accepted: 30 Apr 2025.
Copyright: © 2025 Wang, Bhandary, Griffin, Moore, Li and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Xue Li, Cedars Sinai Medical Center, Los Angeles, United States
Zhiping Paul Wang, Cedars Sinai Medical Center, Los Angeles, United States
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.