IMP3 combined with CD44s, a novel predictor for prognosis of patients with hepatocellular carcinoma

Abstract

Insulin-like growth factor 2 mRNA-binding protein 3 (IMP3) is reported to be re-expressed in malignant tumors and can regulate the expression of multiple genes related to tumor invasion. CD44 standard isoform (CD44s) has been reported to play an important role in facilitating tumor invasion. In this text, we investigate the regulatory function of IMP3 on CD44s and the role of IMP3 and CD44s in predicting the outcomes of patients with hepatocellular carcinoma. IMP3 and CD44s were measured in hepatocellular carcinoma (HCC) tissues by immunohistochemical assay, and survival analysis was conducted among 128 patients. Moreover, we studied the effect of IMP3 on the expression of CD44s and the biological functions of tumor cells in HCC cell lines. Our results showed that the expression of IMP3 was significantly correlated with CD44s expression (r = 0.505, P < 0.001), and both of them correlated with high AFP level, advanced tumor stage and grade, portal vein tumor thrombus, and early tumor recurrence or metastasis. The results of survival analysis exhibited that the 1-, 3-, 5-year disease-free and overall survival rates significantly reduced in IMP3- and CD44s-positive patients, and IMP3 combined with CD44s was an independent prognostic risk factor for HCC. In vitro assay, our results showed that IMP3 promoted HepG2 and MHCC97H cells invading and migrating via regulating CD44s expression. Our findings suggest that IMP3 facilitates HCC aggressiveness through regulating CD44s expression, and IMP3 combined with CD44s can be as a new predictor for unfavorable prognosis in HCC patients.