Screening Of Differentially Expressed LncRNAs And MRNAs In Early And Late Hepatocellular Carcinoma And Bioinformatics Analysis

Background: Hepatocellular carcinoma(HCC)is the most common malignant tumor of digestive system in the world.Its incidence is on the rise year by year with a median survival time of 6-20 months and it is the third leading cause of cancer-related death globally.HCC remains a challenging clinical problem due to its high incidence,high aggressiveness,limited treatment options and poor overall prognosis.Therefore,an urgent need to find potential biomarkers,explore the molecular mechanism of HCC,to provide basis for early prevention and treatment of HCC.As the genome and transcriptome sequencing technology,the rapid development of HCC related gene research is more and more attention,one of the long noncodingRNA(long non codingRNA,lncRNA)has become the focus of research of liver cancer,and lncRNA is a kind of size of more than 200 nucleotides length ofRNA molecules.As a rising star in the field of molecular research,its role in the tumor is more and more attention.In recent years,research has shown that many abnormal expression of lncRNA in cancer related biological processes played an important role,such as the occurrence,proliferation,invasion and metastasis of tumors.They are closely associated with the occurrence of tumor and is expected to be is a new potential related biomarkers of HCC.Objectives: To screen differentially expressed lncRNAs and mRNAs in early and late hepatocellular carcinoma(HCC)in TCGA database and conduct bioinformatics analysis,and to find the lncRNAs acting as a biomarker of early and late HCC.Methods: Base on TCGA dataset,we identify shared DEmRNAs and DElncRNAs between early and late HCC and normal tissue.For the shared DEmRNAs,functional annotation and protein-protein interaction(PPI)network construction were performed,and molecular regulatory networks were constructed.Furthermore,DElncRNAs-DEmRNAs co-expression network of early and late HCC was performed and analyzed,and the key genes with differential expression were screened out.The expression of selected candidate genes was validated by Quantitative real-time polymerase chain reaction(q RT-PCR).Results: A total of 1201 shared DEmRNAs and 162 shared DElncRNAs were identified in both early and late HCC compared with normal controls.Cell cycle,p53 signaling pathway,Retinol metabolism,and Metabolism of xenobiotics by cytochrome P450 were four significantly enriched pathways.Base on the PPI network,CDK1,AURKA,CDC20,PLK1,AURKB,HIST1H2 BG,BUB1B,CCNA2,CCNB1,and CDT1 were key protein.CTD-2510F5.4 and HAND2-AS1 were hub lncRNAs in both early and late HCC.In general,the confirmation results of q RT-PCR were consistent with our integrated analysis.Conclusion: A total of 4 DEmRNAs(CDK1,KIFC1,CENPF,and ECM1)and 2 DElncRNAs(CTD-2510F5.4 and HAND2-AS1)were identified as potential biomarkers for the diagnosis and prognosis of HCC.