Upregulated HOXC8 Expression Is Associated with Poor Prognosis and Oxaliplatin Resistance in Hepatocellular Carcinoma.

ABSTRACT

BACKGROUND: Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide. It is indispensable to understanding molecular mechanisms of HCC progression and to developing clinically useful biomarkers for this disease. AIM: In this article, we examined whether HOXC8 was associated with the poor prognosis of hepatocellular carcinoma and explored the possible underlying mechanism. METHODS: The HOXC8 and Ki67 expression levels in 86 patients with hepatocellular carcinoma were examined using immunohistochemistry. HOXC8 levels in HCC cells were downregulated by siRNA transfection. The cycle progression and cell proliferation status of HCC cells and the oxaliplatin effectiveness were evaluated by flow cytometry and CCK-8 assay. HOXC8, CyclinD1, PCNA, Nkd2, and cleaved caspase-3 levels were detected by western blot. RESULTS: HOXC8 was upregulated in HCC tissues, compared with adjacent non-tumor ones. HOXC8 expression levels in 86 patients with hepatocellular carcinoma were positively correlated with histological grade. Univariate and multivariate survival analysis revealed that HOXC8 was a significant predictor for overall survival of HCC patients. HOXC8 siRNA knockdown delayed the G1-S phase transition, inhibited cell proliferation, and attenuated resistance to oxaliplatin. CONCLUSIONS: HOXC8 promoted HCC proliferation and predicted poor prognosis. Furthermore, upregulated HOXC8 expression was associated with oxaliplatin resistance in hepatocellular carcinoma.