Identification of the role of MCM6 in bladder cancer prognosis, immunotherapy response, and in vitro experimental investigation using multi-omics analysis

Abstract

BackgroundThe tumor-promoting effects of MCM6 in numerous tumors have been widely revealed, yet its specific role in bladder cancer (BLCA) is still elusive. The objective of this research was to explore the underlying impact of MCM6 on BLCA. MethodsIntegrating transcriptomic and proteomic data, MCM6 was identified to be strongly correlated with BLCA through weighted gene co-expression network analysis(WGCNA) and venn analyses. Then, the clinical value of MCM6 was validated with public database data. The different molecular/immune characteristics and the benefit of immunotherapy were also found in MCM6-defined subgroups. Additionally, single-cell RNA sequencing (scRNA-seq) data was choose for quantify MCM6 expression in the distinct BLCA cell types. The biological role of MCM6 were evaluated via in vitro functional experiments. ResultsIt was testified that the MCM6 could distinguish patients outcome in TCGA and GEO cohorts. Moreover, compared with the MCM6 low-expression group, the MCM6 high-expression group was related to more tumor-promoting related pathways, aggressive phenotypes, and benefit from immunotherapy. Analysis of scRNA-seq data resulted in MCM6 was mainly expressed in BLCA epithelial cells and the proportion of MCM6-expressing tumor epithelial cells is higher than the normal epithelial cells. Moreover, vitro experiments demonstrated that MCM6 knockdown repressed proliferation, cell cycle, migration, and invasion of BLCA cells. ConclusionThis research indicated MCM6 is a promising marker for both prognosis and immunotherapy benefit and could promote the cells proliferation, invasion and migration in BLCA.