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The Matrisome Genes From Hepatitis B–Related Hepatocellular Carcinoma Unveiled

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 t...

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Autores principales: Chen, Wei, Desert, Romain, Ge, Xiaodong, Han, Hui, Song, Zhuolun, Das, Sukanta, Athavale, Dipti, You, Hong, Nieto, Natalia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8435279/
https://www.ncbi.nlm.nih.gov/pubmed/34510837
http://dx.doi.org/10.1002/hep4.1741
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author Chen, Wei
Desert, Romain
Ge, Xiaodong
Han, Hui
Song, Zhuolun
Das, Sukanta
Athavale, Dipti
You, Hong
Nieto, Natalia
author_facet Chen, Wei
Desert, Romain
Ge, Xiaodong
Han, Hui
Song, Zhuolun
Das, Sukanta
Athavale, Dipti
You, Hong
Nieto, Natalia
author_sort Chen, Wei
collection PubMed
description 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.
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spelling pubmed-84352792021-09-15 The Matrisome Genes From Hepatitis B–Related Hepatocellular Carcinoma Unveiled Chen, Wei Desert, Romain Ge, Xiaodong Han, Hui Song, Zhuolun Das, Sukanta Athavale, Dipti You, Hong Nieto, Natalia Hepatol Commun Original Articles 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. John Wiley and Sons Inc. 2021-06-16 /pmc/articles/PMC8435279/ /pubmed/34510837 http://dx.doi.org/10.1002/hep4.1741 Text en © 2021 The Authors. Hepatology Communications published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Original Articles
Chen, Wei
Desert, Romain
Ge, Xiaodong
Han, Hui
Song, Zhuolun
Das, Sukanta
Athavale, Dipti
You, Hong
Nieto, Natalia
The Matrisome Genes From Hepatitis B–Related Hepatocellular Carcinoma Unveiled
title The Matrisome Genes From Hepatitis B–Related Hepatocellular Carcinoma Unveiled
title_full The Matrisome Genes From Hepatitis B–Related Hepatocellular Carcinoma Unveiled
title_fullStr The Matrisome Genes From Hepatitis B–Related Hepatocellular Carcinoma Unveiled
title_full_unstemmed The Matrisome Genes From Hepatitis B–Related Hepatocellular Carcinoma Unveiled
title_short The Matrisome Genes From Hepatitis B–Related Hepatocellular Carcinoma Unveiled
title_sort matrisome genes from hepatitis b–related hepatocellular carcinoma unveiled
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8435279/
https://www.ncbi.nlm.nih.gov/pubmed/34510837
http://dx.doi.org/10.1002/hep4.1741
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