Identification and functional analysis of differentially expressed genes in poorly differentiated hepatocellular carcinoma using RNA-seq

Oncotarget. 2017 May 30;8(22):35973-35983. doi: 10.18632/oncotarget.16415.

Abstract

Poorly differentiated (PD) hepatocellular carcinoma (HCC) has a worse prognosis compared to moderately differentiated (MD) and well differentiated (WD) HCC. We aimed to identify differentially expressed genes (DEGs) to explore the mechanism of PD HCC. Transcriptome sequencing was performed on tumor and adjacent non-tumorous tissues of PD, MD and WD HCC patients (3 for each group). DEGs were thus identified and functionally analyzed. Further RT-PCR was performed to validate DEGs specific for PD HCC in 47 pairs of samples (15 for PD, 18 for MD, 14 for WD). A total of 681 PD DEGs were detected, including 368 up-regulated and 313 down-regulated genes. Less DEGs were found for MD and especially for WD HCC. Through bioinformatics analysis, PD HCC DEGs were enriched in liver tissue and liver cancer cells, and in biological process and pathway including metabolism, cell cycle, translation and blood coagulation. Potential drugs and genetic perturbations were found to reverse the cancer condition. The RT-PCR results showed consistency with RNA-seq in the validation of 4 DEGs specific for PD HCC. This study detected and validated DEGs of PD HCC, which provides useful information on molecular mechanism of PD HCC for development of new biomarkers, therapeutic targets and drugs.

Keywords: carcinogenesis; differentially expressed genes; hepatocellular carcinoma; poorly differentiated; transcriptome sequencing.

MeSH terms

  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / pathology*
  • Computational Biology / methods
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / pathology*
  • Neoplasm Grading
  • Reproducibility of Results
  • Transcriptome*