Development And Validation Of A RNA-binding Protein Associated Prognostic Model For Hepatocellular Carcinima

BackgroundHepatocellular carcinoma(HCC)is one of the most common pathological types of primary hepatic carcinoma(PHC).Globally,HCC is the second only to lung cancer as the leading cause of cancer-related death,causing nearly 800,000 deaths each year.In China,HCC is the third leading cause of cancer-related death.The onset of liver cancer is insidious,and most cases of HCC have progressed to the middle or late stage when diagnosed,and the best time for treatment is missed,resulting in a poor prognosis.How to realize early diagnosis and accurate prognosis analysis of liver cancer is a hot topic.RNA-binding protein(RBP)refers to a class of proteins associated with RNA regulation and metabolic process,which plays a key role in post-transcriptional gene regulation.RBP is not only involved in normal physiological activities of the human body,but also participate in the occurrence and development of malignant tumors.Based on a series of bioinformatics analysis,this study attempts to screen out the RBP which related to the prognosis of HCC and construct the prognosis model of HCC,so as to provide a new idea for the diagnosis and treatment of liver HCC,and realizes the quantitative prognosis analysis of HCC.ObjectiveTo explore the expression of RBP in HCC,to screen out the prognostic related RBP and to establish prognostic model to realize quantitative prognostic analysis.Methods1.Transcriptome data and clinical group data related to HCC were downloaded from the TCGA database.2.The differential expression of RBP in normal tissues and HCC tissues was screened by LIMMA software package.3.KEGG pathway enrichment analysis was performed for differential RBPs.4.Univariate and multivariate Cox regression analysis was used to construct the prognosis model of HCC and screen the target RBPs.5.Immunohistochemical staining was used to detect the target RBPs in 100 cases of HCC tissues and paracancerous tissues.6.Combined with the follow-up data of HCC patients,the relationship between the expression of target RBPs and prognosis was explored.Results1.50 normal liver tissue samples and 374 HCC tissue samples from the TCGA database.325 statistically significant RBPs were obtained by Wilcox test.(P<0.05).2.The up-regulation of RBPs was significantly enriched in biological processes such as spliceosome,mRNA surveillance pathway,RNA transport and degradation,ribosome biogenesis,microRNAs,homologous recombination,RNA polymerase and(P<0.05).The down-regulation of RBPs was significantly increased in biological processes such as herpes simplex infection,RNA degradation,ribosome biogenesis,influenza A,hepatitis C,RIG-like receptor signaling pathway,measles,mRNA surveillance pathway,RNA transport and Spliceosome(P<0.05).3.Uni variate and multivariate Cox regression analysis obtained the independent prognosis RBPs of EIF2AK4,PRKDC,DHX37,INTS8 and EEF1E1(P<0.05).4.Model showed good diagnostic and prognostic ability(AUC=0.71,P<0.05),and was an independent prognostic factor for HCC patients(P<0.05).5.Immunohistochemical showed low expression of EIF2AK4 in HCC tissues,and high expression of PRKDC,DHX37,INTS8 and EEF1E1 in HCC tissues,with statistical significance(P<0.05).6.Survival analysis showed that the expression of EIF2AK4 in HCC was positively correlated with the overall survival time of patients(P<0.05),while the expression of PRKDC,DHX37,INTS8 and EEF1E1in HCC was negatively correlated with the overall survival time of patients(P<0.05).Conclusions1.In HCC,RBP affects the occurrence and development of tumors by participating in ribosome biogenesis,RNA transport and degradation,mRNA surveillance pathway,microRNAs,homologous recombination,RNA polymerase,spliceosome,RIG-like receptor signaling pathway.2.EIF2AK4,PRKDC,DHX37,INTS8 and EEF1E1 were independent prognostic factors in HCC patients.3.Compared with the paracancerous tissues,EIF2AK4 is lower expression in HCC tissues and act as a protective factor in HCC patients;PRKDC,DHX37,INTS8 and EEF1E1 are higher expressed in HCC tissues and are risk factors in HCC patients.4.The prognostic model based on five RBPs,EIF 2AK4,PRKDC,DHX37,INTS8 and EEF1E1,can not only quantitatively analyze the survival rate of HCC patients at 1,3 and 5 years,but also realize independent prognostic analysis of HCC patients.