Transcriptome-Based Network Analysis Related to Histone Deacetylase Genes and Identified EMP1 as a Potential Biomarker for Prognosis in Bladder Cancer.

Background: Abnormal expression and function of histone deacetylases (HDACs) are closely associated with the development of bladder cancer (BCa). Systematic elucidation of the role of HDACs in BCa is expected to improve BCa prognosis and treatment strategies.

Methods: We explored the correlation and expression patterns of HDAC family genes in BCa. Consensus clustering was employed to categorize BCa into subtypes based on HDAC expression profiles. Differential analysis, pathway enrichment analysis, and drug responsiveness evaluation were conducted to characterize HDAC subtypes. Then, a prognostic model based on HDAC cluster related genes was constructed and validated across multiple cohorts.

Results: We identified distinct HDAC expression patterns and correlations with immune cell infiltration and enrichment of pathways in cancer, highlighting their role in BCa. Consensus clustering revealed 2 HDAC gene subtypes. Gene cluster 1 showed worse survival, higher clinical stage, and lower immune cell infiltration compared to gene cluster 2. Additionally, pathway enrichment analysis revealed differences in tumor-promoting pathways between the clusters. Moreover, gene cluster 1 exhibited higher resistance to Rho kinase inhibitor drugs. Multi-omic analysis unveiled unique mutation and CNV profiles between the clusters, indicating distinct molecular features. Furthermore, a HDAC gene-related prognostic model demonstrated robust predictive accuracy and identified EMP1 as a key prognostic gene associated with poor survival and enriched metastatic pathways.

Conclusion: Our study provides comprehensive insights into the landscape of HDACs in BCa, elucidating their roles in tumor heterogeneity, immune modulation, drug responsiveness, and molecular features. EMP1 is a potential therapeutic target and prognostic marker for BCa.