Integrated Bioinformatics Analysis Reveals Key Candidate Genes and Pathways Associated With Clinical Outcome in Hepatocellular Carcinoma

Frontiers in Genetics

Jiang-Jiang Qin¹  Xiang-Dong Cheng¹  Kelly Quek²  Runzhe Chen⁴  Chung H. Kok⁶  Weidong Zhang⁹  Jian Yang⁹  Yubin Li⁹  Saisai Tian⁹  Shaowei Mo^1,10 

[1] 0Zhejiang Cancer Hospital, Hangzhou, China;Accenture Applied Intelligence, ASEAN, Singapore, Singapore;Cancer Hospital of the University of Chinese Academy of Sciences, Hangzhou, China;Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, United States;Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States;Discipline of Medicine, Adelaide Medical School, The University of Adelaide, Adelaide, SA, Australia;Institute of Cancer and Basic Medicine, Chinese Academy of Sciences, Hangzhou, China;Precision Medicine Theme, South Australian Health and Medical Research Institute, Adelaide, SA, Australia;School of Pharmacy, Naval Medical University, Shanghai, China;The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China;

关键词: hepatocellular carcinoma;    differentially expression genes;    enrichment analysis;    survival analysis;    prognosis;   

DOI  :  10.3389/fgene.2020.00814

来源: DOAJ

【 摘 要 】

Hepatocellular carcinoma (HCC) accounts for approximately 85–90% of all liver cancer cases and has poor relapse-free survival. There are many gene expression studies that have been performed to elucidate the genetic landscape and driver pathways leading to HCC. However, existing studies have been limited by the sample size and thus the pathogenesis of HCC is still unclear. In this study, we performed an integrated characterization using four independent datasets including 320 HCC samples and 270 normal liver tissues to identify the candidate genes and pathways in the progression of HCC. A total of 89 consistent differentially expression genes (DEGs) were identified. Gene-set enrichment analysis revealed that these genes were significantly enriched for cellular response to zinc ion in biological process group, collagen trimer in the cellular component group, extracellular matrix (ECM) structural constituent conferring tensile strength in the molecular function group, protein digestion and absorption, mineral absorption and ECM-receptor interaction. Network system biology based on the protein–protein interaction (PPI) network was also performed to identify the most connected and important genes based on our DEGs. The top five hub genes including osteopontin (SPP1), Collagen alpha-2(I) chain (COL1A2), Insulin-like growth factor I (IGF1), lipoprotein A (LPA), and Galectin-3 (LGALS3) were identified. Western blot and immunohistochemistry analysis were employed to verify the differential protein expression of hub genes in HCC patients. More importantly, we identified that these five hub genes were significantly associated with poor disease-free survival and overall survival. In summary, we have identified a potential clinical significance of these genes as prognostic biomarkers for HCC patients who would benefit from experimental approaches to obtain optimal outcome.

【 授权许可】

Unknown