Exploring the role of monocarboxylate transporter 4 in diverse KRAS mutation subtypes of colorectal Cancer.

This study explored the therapeutic potential of monocarboxylate transporter 4 (MCT4/SLC16A3) in KRAS-mutant colorectal cancer (CRC). By integrating immunohistochemistry with UCSC Xena database analysis, we identified a distinct MCT4 expression pattern in KRAS-mutant CRC. Cytoplasmic MCT4 expression was positively correlated with KRAS mutation status and mismatch repair (MMR) proficiency, but negatively associated with sex and tumor differentiation. Plasma membranous MCT4 expression was also positively correlated with KRAS mutations and negatively with differentiation grade. Notably, tumors harboring KRAS codon 13 mutations, particularly G13D, showed higher MCT4 expression than those with codon 12 mutations, such as G12D. Kaplan-Meier survival analysis revealed a significant association between high SLC16A3 expression and poor prognosis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses indicated that MCT4 is mainly involved in immune regulation and metabolism-related pathways. Furthermore, CIBERSORT analysis combined with immunohistochemistry confirmed a relationship between KRAS mutations and immune cell infiltration. This is the first study to systematically characterize MCT4 expression across different KRAS-mutant CRC subtypes. Our findings suggest that MCT4 may modulate the tumor immune microenvironment in KRAS-mutant CRC and could serve as a potential target for precision therapy.