Bioinformatics Analysis Reveals an Association Between Cancer Cell Stemness, Gene Mutations, and the Immune Microenvironment in Stomach Adenocarcinoma.

ABSTRACT

Cancer stem cells (CSCs), characterized by infinite proliferation and self-renewal, greatly challenge tumor therapy. Research into their plasticity, dynamic instability, and immune microenvironment interactions may help overcome this obstacle. Data on the stemness indices (mRNAsi), gene mutations, copy number variations (CNV), tumor mutation burden (TMB), and corresponding clinical characteristics were obtained from The Cancer Genome Atlas (TCGA) and UCSC Xena Browser. Tumor purity and infiltrating immune cells in stomach adenocarcinoma (STAD) tissues were predicted using the ESTIMATE R package and CIBERSORT method, respectively. Differentially expressed genes (DEGs) between the high and low mRNAsi groups were used to construct prognostic models with weighted gene co-expression network analysis (WGCNA) and Lasso regression. The association between cancer stemness, gene mutations, and immune responses was evaluated in STAD. A total of 6,739 DEGs were identified between the high and low mRNAsi groups. DEGs in the brown (containing 19 genes) and blue (containing 209 genes) co-expression modules were used to perform survival analysis based on Cox regression. A nine-gene signature prognostic model (ARHGEF38-IT1, CCDC15, CPZ, DNASE1L2, NUDT10, PASK, PLCL1, PRR5-ARHGAP8, and SYCE2) was constructed from 178 survival-related DEGs that were significantly related to overall survival, clinical characteristics, tumor microenvironment immune cells, TMB, and cancer-related pathways in STAD. Gene correlation was significant across the prognostic model, CNVs, and drug sensitivity. Our findings provide a prognostic model and highlight potential mechanisms and associated factors (immune microenvironment and mutation status) useful for targeting CSCs.