Association of Combined MET/HGF Expression With the Colorectal Cancer Immune Microenvironment: An Integrated Immunohistochemical and Multi-Database Analysis.

OBJECTIVE: To validate c-MET protein expression in colorectal cancer (CRC) and assess whether joint MET and hepatocyte growth factor (HGF) transcript expression provides descriptive information on tumor microenvironment features beyond MET alone. METHODS: c-MET protein expression was evaluated by immunohistochemistry in 51 paired CRC and adjacent tissues. The Cancer Genome Atlas (TCGA) and TNMplot datasets assessed MET mRNA expression and clinicopathological associations; Kaplan-Meier Plotter evaluated unadjusted survival; and TIMER (Tumor Immune Estimation Resource) examined purity-adjusted immune correlations. In TCGA colon adenocarcinoma (COAD) and rectal adenocarcinoma (READ) cohorts, samples were divided using cohort-specific median MET and HGF expression. ESTIMATE (Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data) and CIBERSORT (Cell-type Identification by Estimating Relative Subsets of RNA Transcripts) compared inferred tumor purity, immune/stromal scores, and immune-cell composition. These computational estimates were not experimentally validated in this study. RESULTS: MET mRNA was elevated in CRC datasets, and c-MET protein H-scores were higher in CRC than in paired adjacent tissues. MET expression was not associated with the tested clinicopathological variables. High MET expression was associated with shorter overall and relapse-free survival in unadjusted analyzes. In both cohorts, the MET-high/HGF-low group generally showed higher estimated tumor purity and lower immune and stromal scores, whereas the MET-low/HGF-high group showed the converse pattern. Individual immune-cell subset differences were cohort dependent. CONCLUSION: MET mRNA and c-MET protein are elevated in CRC. Joint MET/HGF expression may complement MET-only analysis by retaining discordant patterns associated with inferred tumor-cell and immune/stromal composition. These retrospective, algorithm-derived findings do not establish independent prognostic value, HGF/c-MET pathway activation or causality, or a basis for clinical patient stratification.