The essential role of MTDH in the progression of HCC: a study with immunohistochemistry, TCGA, meta-analysis and in vitro investigation.

Recent studies found that metadherin (MTDH) played an essential role in hepatocellular carcinoma (HCC). Nevertheless, the exact function of MTDH in the pathogenesis of HCC was unclarified. In the present study, we aimed to investigate the clinical significance of MTDH in HCC and its effect on HCC cells. Immunohistochemistry (IHC) was performed to detect MTDH expression in HCC tissues. Data from The Cancer Genome Atlas (TCGA) and ONCOMINE was obtained to examine MTDH expression in HCC and its clinical significance. Meta-analysis was conducted to assess the correlation between MTDH expression and both the prognosis (Overall Survival (OS) or Disease-free Survival (DFS)) and clinicopathological features of HCC via STATA 12.0. In vitro experiments were performed to investigate the role of MTDH in cell growth, caspase-3/7 activity and apoptosis in HCC cells. The MTDH staining was remarkably stronger in HCC tissues than in non-cancer tissues from IHC, TCGA and ONCOMINE data. Moreover, MTDH-positive expression was significantly correlated with pathological grade, distant metastasis and hepatitis B virus (HBV) infection by IHC. For meta-analysis, MTDH expression was indicative of poor OS without heterogeneity in HCC patients. Additionally, MTDH expression was correlated with high-grade histological differentiation, non-vascular invasion and metastasis in HCC. In vitro experiments revealed that MTDH could the inhibit cell growth and activate caspase-3/7 activity and apoptosis in the four HCC cell lines. In conclusion, MTDH expression may serve as a novel targeting strategy for HCC due to its clinical significance and oncogenic function in HCC cells.