Matrix metalloproteinase 12 (MMP12) as an adverse prognostic biomarker of vascular invasion in hepatic cell carcinoma.

Abstract

Vascular invasion is closely associated with tumor recurrence and poor outcomes in hepatocellular carcinoma (HCC). In this study, we evaluated the potential prognostic value of matrix metalloproteinase-12 (MMP12) as a biomarker of vascular invasion in HCC patients. The Gene Expression Omnibus GSE77509 and TCGA Liver Hepatocellular Carcinoma datasets were analyzed to explore the relationships between genes, vascular invasion, and patient survival. The role of MMP12 in HCC was analyzed in terms of DNA methylation, immune cell infiltration, and patient survival, as well as in silico analysis. Overexpression of MMP12 was associated with poor prognosis in HCC patients with vascular invasion. MMP12 was identified as an independent predictor of overall survival (OS) (HR 2.543; 95% CI 1.224, 5.285; p = 0.012) and disease-free survival (DFS) (HR 2.034; 95% CI 1.160, 3.566; p = 0.013) in multivariate Cox analysis in HCC patients. MMP12 expression, vascular invasion, tumor status, and AJCC T stage were independent predictors of OS with a concordance index (C-index) of 0.713 (95% CI, 0.671, 0.756). MMP12 expression was related to hypomethylation status and positively correlated with tumor immune cell infiltration and the expression of immune cell-related biomarkers. Upregulation of MMP12 was associated with poor prognosis and vascular invasion in HCC. These data suggest that MMP12 may have potential as a therapeutic target and biomarker in HCC.