Research Paper Volume 12, Issue 1 pp 204—223

The correlation and role analysis of COL4A1 and COL4A2 in hepatocarcinogenesis

Yanli Liu1,2, , Jiaye Zhang4,5, , Yan Chen4,5, , Hasan Sohel4,5, , Xinrong Ke1,2, , Jingqi Chen1,2,3, , Yin-Xiong Li4,5,6,7,8, ,

  • 1 Stem Cell Translational Medicine Center, State Key Laboratory of Respiratory Disease, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, China
  • 2 Stem Cell Translational Medicine Center, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, China
  • 3 Department of Medical Oncology, Guangzhou Medical University, Guangzhou, China
  • 4 Institute of Public Health, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China
  • 5 Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China
  • 6 Guangdong Provincial Key Laboratory of Biocomputing, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China
  • 7 Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou, China
  • 8 University of Chinese Academy of Sciences, Beijing, China

Received: July 25, 2019       Accepted: December 5, 2019       Published: January 5, 2020      

https://doi.org/10.18632/aging.102610
How to Cite

Copyright © 2020 Liu 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.

Abstract

Liver fibrosis biomarker, Type IV collagen, may function as hepatocarcinogenesis niche. However, among the six isoforms, the isoforms providing tumor microenvironment and their regulatory network are still unclarified. Based on bioinformatics analysis of hundreds of HCC transcriptome datasets from public databases, we found that COL4A1/2 expressions were significantly correlated with hepatocarcinogenesis, progression, and prognosis. The expressions of COL4A1/2 were significantly upregulated in the preneoplastic and HCC tissues compared with normal tissues. Moreover, the overexpression of COL4A2 was highly correlated with shorter progression-free survival in HCC patients. Bioinformatics analysis also generates an interactive regulatory network in which COL4A1/2 directly binding to integrin alpha-2/beta-1 initiates a sequentially and complicated signaling transduction, to accelerate cell cycle and promote tumorigenesis. Among those pathways, the PI3K-Akt pathway is significantly enriched in cooperative mutations and correlation analysis. This suggests that the key activated signaling is PI3K-Akt pathway which severing as the centerline linked with other pathways (Wnt and MAPK signaling) and cell behaviors signaling (cell cycle control and cytoskeleton change). Switching extracellular matrix collagen isoform may establish pro-tumorigenic and metastatic niches. The findings of COL4A1/2 and related signaling networks are valuable to be further investigated that may provide druggable targets for HCC intervention.

Abbreviations

TCGA: The Cancer Genome Atlas; KEGG: Kyoto Encyclopedia of Genes and Genomes; GO: Gene Ontology; GSEA: Gene Set Enrichment Analysis; GEO: Gene Expression Omnibus; ECM: Extracellular matrix; SRF: Serum response factor; AML1: RUNX1, RUNX family transcription factor 1; CNA: Copy-number alterations; AFP-L3: Alpha fetal protein binding fraction; DCP: Des-γ-carboxyprothrombin; GPC3: Glypican-3; OPN: Osteopontin; GP73: Golgi protein-73; SCCA: Squamous cell carcinoma antigen; SuPAR: Soluble urokinase plasminogen activator receptor; MDK: Midkine; TRX: Thioredoxins.