单位:[1]Department of Pathology, University of Illinois at Chicago, Chicago, IL, USA[2]Experimental and Translational ResearchCenter, Beijing Friendship Hospital, Capital Medical University, Beijing, China首都医科大学附属北京友谊医院[3]Department of Medicine, Division of Gastroenterologyand Hepatology, University of Illinois at Chicago, Chicago, IL, USA.
Chronic hepatitis B virus (HBV) infection changes the composition of the extracellular matrix (ECM) and enables the onset and progression of hepatocellular carcinoma (HCC). The ensemble of ECM proteins and associated factors is a major component of the tumor microenvironment. Our aim was to unveil the matrisome genes from HBV-related HCC. Transcriptomic and clinical profiles from 444 patients with HBV-related HCC were retrieved from the Gene Expression Omnibus (GEO) and Cancer Genome Atlas (TCGA) repositories. Matrisome genes associated with HBV-related hepatocarcinogenesis, matrisome gene modules, HCC subgroups, and liver-specific matrisome genes were systematically analyzed, followed by identification of their biological function and clinical relevance. Eighty matrisome genes, functionally enriched in immune response, ECM remodeling, or cancer-related pathways, were identified as associated with HBV-related HCC, which could robustly discriminate HBV-related HCC tumor from nontumor samples. Subsequently, four significant matrisome gene modules were identified as showing functional homogeneity linked to cell cycle activity. Two subgroups of patients with HBV-related HCC were classified based on the highly correlated matrisome genes. The high-expression subgroup (15.0% in the TCGA cohort and 17.9% in the GEO cohort) exhibited favorable clinical prognosis, activated metabolic activity, exhausted cell cycle, strong immune infiltration, and lower tumor purity. Four liver-specific matrisome genes (F9, HPX [hemopexin], IGFALS [insulin-like growth-factor-binding protein, acid labile subunit], and PLG [plasminogen]) were identified as involved in HBV-related HCC progression and prognosis. Conclusion: This study identified the expression and function of matrisome genes from HBV-related hepatocarcinogenesis, providing major insight to understand HBV-related HCC and develop potential therapeutic opportunities.
基金:
U.S. Public Health Service Grant from the National Institute of Diabetes and Digestive and Kidney Diseases [R01 DK111677]
第一作者单位:[1]Department of Pathology, University of Illinois at Chicago, Chicago, IL, USA[2]Experimental and Translational ResearchCenter, Beijing Friendship Hospital, Capital Medical University, Beijing, China
通讯作者:
通讯机构:[1]Department of Pathology, University of Illinois at Chicago, Chicago, IL, USA[3]Department of Medicine, Division of Gastroenterologyand Hepatology, University of Illinois at Chicago, Chicago, IL, USA.[*1]Department of Pathology, University of Illinois at Chicago 840 S. Wood St., Suite 130 CSN, MC 847 Chicago, IL 60612, US