The Correlation Between IMP3and CD44s Expression With The Prognosis Of Patients With Hepatocelluar Carcinoma After Hepatectomy

Purpose Insulin-like growth factor2mRNA binding protein3(IMP3) is reported to be expressed in embryonic tissue of human, but not detected in adult tissue. Presently, it is reported that IMP3is re-expressed in some malignant tumors and can regulate the expression of multiple genes related to tumor invasion. CD44s molecule is a trans-membrane glycoprotein and it has been reported to play an important role in facilitating tumor invasion. In this text, we investigate the regulatory function of IMP3on CD44s and the role of IMP3and CD44s in predicting the outcomes of patients with hepatocelluar carcinoma.Methods We studied the effect of IMP3on the expression of CD44s and the biological functions of tumor cells in HCC cell lines by Western Blot assay, Real-time PCR assay and Transwell assay. IMP3and CD44s were measured in HCC tissues by Immunohistochemical assay and Real-time PCR assay. Survival analysis was conducted among128patients by Kaplan-Meier method and the differences were examined by the log-rank test. Cox proportional hazards regression model was used to conducted univariate and multivariate analysis for disease-free and overall survival of HCC patients.Results In vitro assay, our results showed that both IMP3and CD44s were highly expressed in high aggressive HCC cell lines. The expression of IMP3and CD44s were significantly correlated with each other in HCC cells, and IMP3promoted HepG2and MHCC97H cells invading and migrating via regulating CD44s expression. In HCC tissues, our results showed that the expression of IMP3was also significantly correlated with CD44s expression (r=0.505, P<0.001). The analysis of the correlation between IMP3and CD44s and clinical characteristics of HCC showed that both of them were significantly correlated with high AFP level (IMP3, P=0.018; CD44s, P=0.042), advanced tumor stage (IMP3, P=0.003; CD44s, P=0.011) and grade (IMP3, P<0.001; CD44s, P=0.009), portal vein tumor thrombus (IMP3, P=0.027; CD44s, P=0.039), and early tumor recurrence or metastasis (IMP3, P<0.001; CD44s, P<0.001). The results of survival analysis exhibited that the1-,3-,5-year disease-free and overall survival rates significantly reduced in IMP3and CD44s positive patients compared with those of IMP3and CD44s negative patients, respectively, and when IMP3and CD44s were taken into consideration together, the predictive range was extended and the sensitivity was improved. The result of multivariate analysis revealed that IMP3combined with CD44s was an independent prognostic risk factor for HCC (OS, HR=1.845, P=0.014; DFS, HR=2.086, P=0.002).Conclusions Our findings suggest that IMP3facilitates HCC aggressiveness through regulating CD44s expression and IMP3combined with CD44s can be as a new predictor for unfavorable prognosis in HCC patients.