Role of Matrix Metallopeptidase 12 in the Development of Hepatocellular Carcinoma

Abstract

Objective The aim of this study was to investigate the role of matrix metallopeptidase 12 (MMP-12) in the development of hepatocellular carcinoma (HCC). Materials and Methods: A total of 343 HCC patients were retrospectively analyzed. MMP-12 expression was detected by immunohistochemical staining and the correlation between MMP-12 expression and clinical features was analyzed. Serum interleukin-6 (IL-6) and IL-10 levels were detected by an enzyme-linked immunosorbent assay (ELISA). Survival analysis was performed using the Kaplan–Meier method and PD-L1 expression in T cells was detected by flow cytometry. Results: MMP-12 expression in HCC tissues showed no correlation with age, gender, viral infection, cirrhosis, Child-Pugh score, alpha-fetoprotein levels, or Barcelona-Clinic Liver Cancer stage. However, higher levels of MMP-12 expression were correlated with increased tumor size, poorer tumor cell differentiation, higher TNM stage, and poorer prognosis. Moreover, MMP-12 expression was positively correlated with PD-L1 expression. Further analysis indicated that the regulation of PD-L1 expression by MMP-12 may occur through the IL-6-signaling pathway. Conclusions: Higher levels of MMP-12 expression indicated a poorer prognosis. PD-L1 expression was positively correlated with MMP-12 expression, indicating that MMP-12 may promote the development of HCC through the up-regulation of PD-L1.

Keywords

• matrix metallopeptidase 12
• hepatocellular carcinoma
• pathological characteristics