Research Paper Volume 12, Issue 6 pp 5439—5468

Identification of hub genes in hepatocellular carcinoma using integrated bioinformatic analysis

Shengni Hua1, *, , Zhonghua Ji2, *, , Yingyao Quan1, , Meixiao Zhan1, , Hao Wang1, , Wei Li1, , Yong Li1, , Xu He1, , Ligong Lu1, ,

  • 1 Zhuhai Interventional Medical Center, Zhuhai Precision Medical Center, Zhuhai People’s Hospital, Zhuhai Hospital Affiliated with Jinan University, Zhuhai 519000, China
  • 2 Department of Anesthesiology, Zhuhai People’s Hospital, Zhuhai Hospital Affiliated with Jinan University, Zhuhai 519000, China
* Equal contribution

Received: August 16, 2019       Accepted: February 19, 2020       Published: March 26, 2020
How to Cite

Copyright © 2020 Hua et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


The molecular mechanisms underlying hepatocellular carcinoma (HCC) progression remain largely undefined. Here, we identified 176 commonly upregulated genes in HCC tissues based on three Gene Expression Omnibus datasets and The Cancer Genome Atlas (TCGA) cohort. We integrated survival and methylation analyses to further obtain 12 upregulated genes for validation. These genes were overexpressed in HCC tissues at the transcription and protein levels, and increased mRNA levels were related to higher tumor grades and cancer stages. The expression of all markers was negatively associated with overall and disease-free survival in HCC patients. Most of these hub genes can promote HCC proliferation and/or metastasis. These 12 hub genes were also overexpressed and had strong prognostic value in many other cancer types. Methylation and gene copy number analyses indicated that the upregulation of these hub genes was probably due to hypomethylation or increased gene copy numbers. Further, the methylation levels of three genes, KPNA2, MCM3, and LRRC1, were associated with HCC clinical features. Moreover, the levels of most hub genes were related to immune cell infiltration in HCC microenvironments. Finally, we identified three upregulated genes (KPNA2, TARBP1, and RNASEH2A) that could comprehensively and accurately provide diagnostic and prognostic value for HCC patients.


HCC: hepatocellular carcinoma; GEO: Gene Expression Omnibus; TCGA: The Cancer Genome Atlas; DEGs: differentially-expressed genes; PPI: protein–protein interaction; GO: Gene Ontology; MCODE: Molecular Complex Detection; PCA: principal component analysis; OS: overall survival; DFS: disease free survival.