Molecular Subtypes based on Mitochondrial Oxidative Stress-related Gene Signature and Tumor Microenvironment Infiltration Characterization of Colon Adenocarcinoma

BACKGROUND: As the most common subtype of colorectal cancer, colorectal adenocarcinoma (COAD) still needs better prognostic stratification methods and new intervention targets. The mitochondrial stress response, linked to mitochondrial homeostasis and cancer metabolism, warrants further investigation. METHODS: We identified mitochondrial oxidative stress-related genes (MOS) associated with COAD prognosis through the TCGA and GEO databases. Molecular subtype characteristics were identified based on MOS gene signatures, and an MOS scoring system was established to comprehensively evaluate its clinical value. Additionally, the effect of one of the screened genes, NDRG1, was investigated through a series of in vitro experiments, including Western blot, qRT-PCR, CCK8 assay, clone formation, and Transwell assay, to explore its impact on COAD proliferation and migration ability. RESULTS: Our analysis revealed that MOS gene signatures effectively distinguished molecular subtypes of COAD, and the MOS scoring system was found to be independent in predicting prognosis. Evaluation of microenvironment infiltration characteristics, mutation characteristics, immunotherapy response, and drug sensitivity analysis further suggested the potential clinical utility of this study. In vitro experimental results showed that NDRG1 significantly affected the proliferation and migration of COAD cells, partially verifying the reliability of our bioinformatics analysis. CONCLUSION: This study provides a novel perspective on the role of mitochondrial oxidative stress in COAD, proposing innovative prognostic evaluation methods and potential therapeutic targets, thus offering new directions for the clinical treatment of COAD.