Integrated multi-omics analysis reveals key genetic, metabolic, and microbial drivers in bladder cancer insights into molecular subtyping and therapeutic approaches: A tumor marker prognostic study

Background: Bladder cancer (BLCA) is a common malignancy with significant impact on patient health. The aim of this study was to explore the potential mechanisms of BLCA through a combination of multi-omics and single-cell analyses. Methods: In this study, samples from BLCA and paracancerous tissues were collected for transcriptome, whole-exome sequencing, metabolome and intratumoural microbiome sequencing. These data were then co-analyzed with publicly available datasets to identify and analyze key genes, metabolites and microbiomes as well as their regulatory mechanisms in the pathogenesis of BLCA. Different BLCA clusters were then identified on the basis of key genes. Differences among the clusters were then investigated in terms of biological pathways, immunological microenvironment, genetic alterations, immunotherapy and drug susceptibility. The prognostic value of the key genes was then analyzed using publicly available data, and their molecular regulatory mechanisms were further investigated. Finally, the expression patterns of the key genes were observed at the single cell level and key cells were identified. Results: In this paper, three key genes (AHNAK, CSPG4, and NCAM1), 90 key metabolites and two key microorganisms (Sphingomonas koreensis and Rhodospirillaceae) were identified in a multi-omics analysis. Of these, key genes and key metabolites were negatively correlated. The BLCA samples from transcriptome sequencing were then divided into cluster 1 and cluster 2 based on key genes. Single-cell analysis identified nine cell types, with fibroblasts exhibiting the highest expression of key genes, thus establishing fibroblasts as the key cell in this study. Notably, AHNAK expression was higher in fibroblast subtypes. Conclusion: The combined multi-omics analysis revealed a significant correlation between three key genes (AHNAK, CSPG4, and NCAM1) and multiple key metabolites and key microorganisms, which offering a new reference and theoretical support for the treatment and research of BLCA.