Expression And Significance Of IMP3 In Hepatocellular Carcinoma

Background:Hepatocellular carcinoma is one of the most common malignancies.Because of the characteristic of high mortality,hepatocellular carcinoma is no effective therapy in clinic currently,which breakthrough progress is expected to gene therapy.IMP3（Insulin like growth factor 2 mRNA binding protein 3）regulate mRNA localization,reverse transcription and translation.Recent studies have demonstrated that IMP3 contribute to promote cell proliferation,adhesion,migration and invasion in various cancers,but there has a lack of systematic reviews in HCC,therefore,we need to make further efforts to explore the role of IMP3 in the development of HCC.Methods:We screened literatures with cancer survival data from Pubmed database,and then performed meta analysis to study the association between IMP3expression and multiple tumor prognosis;Clinicopathological and expression data of HCC patients and controls were obtained from TCGA database to do differential expression analysis,we also downloaded HCC gene chip data from GEO database to verify IMP3 expression level in HCC and paracancerous tissue.and then we used statistical analysis to research the association between IMP3 expression and survival and clinical pathological features of HCC patients;Also,we explored the biological function of IMP3 in HCC by molecular mechanisms and cell experiments.Results:Meta analysis demonstrated that the high expression of IMP3 was positively correlated with the poor prognosis of various tumors,and HCC had the highest hazard ratio(HR=9.76,95%CI=3.10-30.74,P<1×10^-5);By analyzing TCGA HCC datasets,we found that IMP3 was significantly overexpressed in HCC tissues compared with paracancerous tissues(t=6.66,adj.P=7.51×10^-10),and it was verified by analyzing GEO datasets(zSco=15.66,P=5.64×10^-65).Kaplan-Meier analysis showed that high expression of IMP3 predicted poor overall survival and disease free survival in HCC patients(log-rank P_OS=0.0337,log-rank P_DFS=0.0203);and Chi-square test indicated IMP3 expression was significantly correlated with histological grade（P=0.002）and HCC icluster（P=0.01）,but no significant correlation with age,gender and TNM stage.And further using logistic regression analysis to control confounding factors found that IMP3 expression was still significantly associated with histological grade（P=0.002）.Cell experiments showed that knockdown IMP3 expression in SMMC7721 and Huh7 cell lines could significantly inhibited HCC cell proliferation and cell growth(P_Huh7=0.007,P_SMMC7721=0.012).Conclusions:Our study revealed that IMP3 was upregulated in HCC and the high expression of IMP3 could make poor prognosis in HCC patients,it may be due to IMP3 can promote cell proliferation.In summary,IMP3 might play a important role in tumor progression in HCC,and could be used as a prognostic marker for HCC.