Identification of the Pathogenic Biomarkers for Hepatocellular Carcinoma Based on RNA-seq Analyses

Pathol Oncol Res. 2019 Jul;25(3):1207-1213. doi: 10.1007/s12253-019-00596-2. Epub 2019 Jan 24.

Abstract

The purpose of this study was to explore potential biomarkers in the diagnosis of hepatocellular carcinoma (HCC) based on RNA-seq. The microarray data GSE98269 were downloaded from the GEO database, including the miRNA, mRNA and lncRNA expression profiles of 3 HCC tissues and 3 normal liver tissues from 3 HCC patients. The limma package was used to identify the differentially expressed miRNAs (DEMs) and the differentially expressed lncRNAs in HCC tissues compared with normal liver tissues. Database of DAVID, KEGG PATHWAY and Reactome were used to perform the functional and pathway enrichment. Putative targets for DEMs, and the miRNA-gene pairs were predicted via the miRWalk V2.0 database. The protein-protein pairs of DEGs were screened via String software. The expression features of the differentially expressed lncRNAs were analyzed. The regulated network of DEGs and DEMs were constructed, and related genes and miRNAs were detected in the HCC tissues and normal liver samples with Q-PCR. A total of 678 DEGs, 32 DEMs and 411 differential expressed lncRNAs were identified. The DEGs were enriched in 196 GO terms and 79 pathways. 38 negative regulation miRNA-gene pairs and 1205 protein-protein interactions were screened out, and the regulated network was constructed based on them. KNG1, CDK1, EHHADH, CYP3A4, hsa-miR-199a-5p and hsa-miR-455-3p might be biomarkers in the occurrence of HCC.

Keywords: Early diagnosis; Hepatocellular carcinoma (HCC); RNA-seq.

MeSH terms

  • Biomarkers, Tumor / genetics*
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / pathology
  • Computational Biology / methods*
  • Gene Expression Profiling
  • Gene Regulatory Networks
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / pathology
  • MicroRNAs / genetics*
  • RNA, Messenger / genetics*
  • RNA-Seq / methods*
  • Software

Substances

  • Biomarkers, Tumor
  • MicroRNAs
  • RNA, Messenger