Anti-oncogenic and immunological functions of ATP23 in CMS4 colon adenocarcinoma based on a machine learning computational framework.

BACKGROUND: Consensus Molecular Subtype (CMS) 4 and BRAF mutations are poor prognostic indicators for colon adenocarcinoma (COAD). Although the prevalence of BRAF-mutated COAD is higher in the CMS1 subtype, we have identified certain cases of CMS4 subtypes in patients with BRAF mutations. However, there is currently a lack of research exploring whether this particular type of COAD exhibits a worse prognosis and unraveling its underlying mechanism. METHODS: This retrospective study analyzed the transcriptome profiles and clinical parameters of COAD patients from six public datasets. Kaplan-Meier plots and bioinformatics methods predicted the correlation between ATP23 expression and patient survival. We compared enriched pathways, genomic mutations, immune cell infiltration, copy number alterations, cell-cell communication, and TIDE scores between ATP23-high and ATP23-low groups. Furthermore, in vitro experiments verified the potential roles of ATP23 in COAD. RESULTS: The expression of ATP23 was significantly lower in tumor tissues, particularly in the CMS4 subtype. No significant correlation was observed between ATP23 expression and clinical characteristics or molecular mutations in COAD. Higher ATP23 levels were associated with improved survival rates in COAD patients. In vitro experiments indicated that ATP23 inhibits the proliferation, migration, and invasion capabilities of COAD cells. Moreover, decreased ATP23 expression may impair oxidative phosphorylation in T cells, contributing to the formation of an immune-evasive microenvironment, and potentially leading to reduced efficacy of both immunotherapy and conventional chemotherapy. CONCLUSIONS: ATP23 is a potential prognostic marker for COAD patients. Reduced ATP23 expression may inhibit oxidative phosphorylation in T cells and contribute to the formation of an immunosuppressive microenvironment.