Screening Of The Overexpressed Genes In Hepatocellular Carcinoma Based On The Gene Expression Profiles

Objective:Hepatocellular carcinoma（HCC）is one of the five most common cancers in the world.About 50%of the new cases occur in China every year,ranking the second leading cause of cancer death in China.Although the diagnosis and prognosis of HCC in our country have improved significantly compared with the past,the treatment effect still needs to be improved.In recent years,the tumor molecular targeted therapy has changed greatly.But in the field of HCC treatment,multi-targeted drugs Sorafenib and regorafenib are still the only molecularly targeted drugs approved by the FDA and CFDA at present.However,their clinical application have the problems of low efficiency,lack effective predictive markers,large side effects,and secondary resistance.Therefore,the search for potential molecular targets for HCC therapy has important clinical implications.The purpose of this study is to screen the gene spectrum with the most obvious up-regulation in HCC,and provide basis for the development of HCC molecular targeted drugs.Methods:In this study,the total gene expression profiles of 93 cases of HCC and paracancer liver tissue were detected by Affymetrix U133 Plus2.0 platform,Highly expressed genes were screened out in hepatocellular carcinoma.The level of gene expression was treated with log₂ logarithm,with?x±s said.Paired t-test was used to compare the mRNA expression of HCC and paired adjacent liver tissue.Screening of overexpressed genes with P<0.001 for statistical significance.The correlation between gene and clinicopathological factors was analyzed byχ² test with P<0.05.GCOS1.4 software was used in the processing of gene expression data.R 3.01 and STATA 13 software were used for statistical analysis.Results:1.The highest expression of ten genes in HCC:Comparative analysis of gene expression profiles in 93 cases of HCC and paraneoplastic paracancerous liver tissues,The highest expression of 10 genes in HCC were CDKN3,CCL20,PTTG1,MELK,PRMT1,TOP2A,TPX2,SMYD3,TMEM106C and UCK2.The genes were up-regulated from 25.2 times to 44.6 times with P values≤2.0×10^-22.2.Correlation between genes and clinicopathological factors:The median gene expression level as the boundary in HCC.The 93 cases of HCC were divided into high expression and low expression of two groups.Then analysis of correlation between CDKN3,CCL20,PTTG1,MELK,PRMT1,TOP2A,TPX2,SMYD3,TMEM106C,UCK2 and Age,gender,postoperative AFP level,HBV infection,cirrhosis,number and size of tumors,vascular invasion,tumor envelope,Edmondson-Steiner classification,TMN staging.We found that the high expression of CCL20,PRMT1 and UCK2 genes was positively correlated with high serum AFP levels.The high expression of CCL20,PTTG1,PRMT1 and UCK2 genes was positively correlated with the high grade of histology Edmondson-Steiner.The high expression of CCL20 gene is positively correlated with high TNM staging（all P<0.05）.The high expression of SMYD3 gene was positively correlated with chronic hepatitis B infection and no vascular invasion（all P<0.05）.However,there was no significant correlation between the expression of CDKN3,MELK,TPX2,TMEM106C and clinical pathological parameters（all P>0.05）.Conclusion:1.This study screened the Top10 gene with the most significant up-regulated expression in HCC:CDKN3、CCL20、PTTG1、MELK、PRMT1、TOP2A、TPX2、SMYD3、TMEM106C and UCK2.The high expression of CCL20,PRMT1,UCK2,TOP2A and PTTG1 is related to the bad biological characteristics of HCC.2.Previous studies have shown that specific inhibitors against CDKN3,CCL20,PTTG1,MELK,PRMT1,TOP2A,TPX2 and SMYD3 exhibit antitumor activity in various tumors.The HCC molecular targeted therapy using these genes as targets has potential clinical applications.3.The abnormal high expression of TMEM106C and UCK2 genes in HCC is the first report at home and abroad,which provides potential targets for the research and development of HCC molecular targeting drugs.