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Metabolism‐associated molecular classification of hepatocellular carcinoma
Hepatocellular carcinoma (HCC) is a disease with unique management complexity because it displays high heterogeneity of molecular phenotypes. We herein aimed to characterize the molecular features of HCC by the development of a classification system that was based on the gene expression profile of m...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7138397/ https://www.ncbi.nlm.nih.gov/pubmed/31955511 http://dx.doi.org/10.1002/1878-0261.12639 |
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author | Yang, Chen Huang, Xiaowen Liu, Zhicheng Qin, Wenxin Wang, Cun |
author_facet | Yang, Chen Huang, Xiaowen Liu, Zhicheng Qin, Wenxin Wang, Cun |
author_sort | Yang, Chen |
collection | PubMed |
description | Hepatocellular carcinoma (HCC) is a disease with unique management complexity because it displays high heterogeneity of molecular phenotypes. We herein aimed to characterize the molecular features of HCC by the development of a classification system that was based on the gene expression profile of metabolic genes. Integrative analysis was performed with a metadata set featuring 371 and 231 HCC human samples from the Cancer Genome Atlas and the International Cancer Genome Consortium, respectively. All samples were linked with clinical information. RNA sequencing data of 2752 previously characterized metabolism‐related genes were used for non‐negative matrix factorization clustering, and three subclasses of HCC (C1, C2, and C3) were identified. We then analyzed the metadata set for metabolic signatures, prognostic value, transcriptome features, immune infiltration, clinical characteristics, and drug sensitivity of subclasses, and compared the resulting subclasses with previously published classifications. Subclass C1 displayed high metabolic activity, low α‐fetoprotein (AFP) expression, and good prognosis. Subclass C2 was associated with low metabolic activities and displayed high expression of immune checkpoint genes, demonstrating drug sensitivity toward cytotoxic T‐lymphocyte‐associated protein‐4 inhibitors and the receptor tyrosine kinase inhibitor cabozantinib. Subclass C3 displayed intermediate metabolic activity, high AFP expression level, and bad prognosis. Finally, a 90‐gene classifier was generated to enable HCC classification. This study establishes a new HCC classification based on the gene expression profiles of metabolic genes, thereby furthering the understanding of the genetic diversity of human HCC. |
format | Online Article Text |
id | pubmed-7138397 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-71383972020-04-08 Metabolism‐associated molecular classification of hepatocellular carcinoma Yang, Chen Huang, Xiaowen Liu, Zhicheng Qin, Wenxin Wang, Cun Mol Oncol Research Articles Hepatocellular carcinoma (HCC) is a disease with unique management complexity because it displays high heterogeneity of molecular phenotypes. We herein aimed to characterize the molecular features of HCC by the development of a classification system that was based on the gene expression profile of metabolic genes. Integrative analysis was performed with a metadata set featuring 371 and 231 HCC human samples from the Cancer Genome Atlas and the International Cancer Genome Consortium, respectively. All samples were linked with clinical information. RNA sequencing data of 2752 previously characterized metabolism‐related genes were used for non‐negative matrix factorization clustering, and three subclasses of HCC (C1, C2, and C3) were identified. We then analyzed the metadata set for metabolic signatures, prognostic value, transcriptome features, immune infiltration, clinical characteristics, and drug sensitivity of subclasses, and compared the resulting subclasses with previously published classifications. Subclass C1 displayed high metabolic activity, low α‐fetoprotein (AFP) expression, and good prognosis. Subclass C2 was associated with low metabolic activities and displayed high expression of immune checkpoint genes, demonstrating drug sensitivity toward cytotoxic T‐lymphocyte‐associated protein‐4 inhibitors and the receptor tyrosine kinase inhibitor cabozantinib. Subclass C3 displayed intermediate metabolic activity, high AFP expression level, and bad prognosis. Finally, a 90‐gene classifier was generated to enable HCC classification. This study establishes a new HCC classification based on the gene expression profiles of metabolic genes, thereby furthering the understanding of the genetic diversity of human HCC. John Wiley and Sons Inc. 2020-01-29 2020-04 /pmc/articles/PMC7138397/ /pubmed/31955511 http://dx.doi.org/10.1002/1878-0261.12639 Text en © 2020 The Authors. Published by FEBS Press and John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Yang, Chen Huang, Xiaowen Liu, Zhicheng Qin, Wenxin Wang, Cun Metabolism‐associated molecular classification of hepatocellular carcinoma |
title | Metabolism‐associated molecular classification of hepatocellular carcinoma |
title_full | Metabolism‐associated molecular classification of hepatocellular carcinoma |
title_fullStr | Metabolism‐associated molecular classification of hepatocellular carcinoma |
title_full_unstemmed | Metabolism‐associated molecular classification of hepatocellular carcinoma |
title_short | Metabolism‐associated molecular classification of hepatocellular carcinoma |
title_sort | metabolism‐associated molecular classification of hepatocellular carcinoma |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7138397/ https://www.ncbi.nlm.nih.gov/pubmed/31955511 http://dx.doi.org/10.1002/1878-0261.12639 |
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