TPX2 as a novel prognostic biomarker for hepatocellular carcinoma.

Abstract

Targeting protein for Xenopus kinesin-like protein 2 (TPX2) is a microtubule-associated protein that impacts spindle assembly in human cells. Several studies have shown that the overexpression of TPX2 is correlated with multiple tumor types. However, the role of TPX2 in hepatocellular carcinoma (HCC) remains undetermined. TPX2 expression was detected by quantitative reverse transcription polymerase chain reaction and immunoblotting in six cell lines and 130 pairs of HCC and adjacent non-cancerous liver tissues. Matrix metalloproteinase (MMP)2 and MMP9 expression was detected by immunohistochemistry to evaluate their correlations with TXP2. TPX2 siRNA was used to knock down TPX2 expression, and cell migration and invasion were determined. Moreover, clinical significance of TPX2 in HCC was analyzed. TPX2 expression was found to be obviously higher in HCC tissues than that in non-tumor tissues. Elevated TPX2 expression was observed in HCC cell lines as compared with that in a non-transformed hepatic cell line. Clinical analysis indicated that TPX2 expression in the HCC tissues was evidently correlated with the tumor-node-metastasis stage, tumor number and tumor differentiation. TPX2 is a novel prognostic marker for predicting 5-year overall survival and disease-free survival of HCC patients. TPX2 expression was positively correlated with MMP2 and MMP9. In vitro studies found that TPX2 knockdown prominently reduced cell invasion and migration and decreased phosphorylated AKT, MMP2 and MMP9 expression in MHCC-97H cells. Overexpression of TPX2 was associated with clinicopathological characteristics and poor patient outcomes. TPX2 may serve as a novel prognostic marker for HCC.