A Minimal Subset of Seven Genes Associated with Tumor Hepatocyte Differentiation Predicts a Poor Prognosis in Human Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is a deadly cancer worldwide as a result of a frequent late diagnosis which limits the therapeutic options. Tumor progression in HCC is closely correlated with the dedifferentiation of hepatocytes, the main parenchymal cells in the liver. Here, we hypothesized that the...

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Autores principales:	Matthis Desoteux, Corentin Louis, Kevin Bévant, Denise Glaise, Cédric Coulouarn
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	hepatocellular carcinoma prognosis signature differentiation overall survival integrative transcriptomics Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/d7fa1cd5c2244985a5a60004b9d7a54f
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spelling	oai:doaj.org-article:d7fa1cd5c2244985a5a60004b9d7a54f2021-11-25T17:01:44ZA Minimal Subset of Seven Genes Associated with Tumor Hepatocyte Differentiation Predicts a Poor Prognosis in Human Hepatocellular Carcinoma10.3390/cancers132256242072-6694https://doaj.org/article/d7fa1cd5c2244985a5a60004b9d7a54f2021-11-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/22/5624https://doaj.org/toc/2072-6694Hepatocellular carcinoma (HCC) is a deadly cancer worldwide as a result of a frequent late diagnosis which limits the therapeutic options. Tumor progression in HCC is closely correlated with the dedifferentiation of hepatocytes, the main parenchymal cells in the liver. Here, we hypothesized that the expression level of genes reflecting the differentiation status of tumor hepatocytes could be clinically relevant in defining subsets of patients with different clinical outcomes. To test this hypothesis, an integrative transcriptomics approach was used to stratify a cohort of 139 HCC patients based on a gene expression signature established in vitro in the HepaRG cell line using well-controlled culture conditions recapitulating tumor hepatocyte differentiation. The HepaRG model was first validated by identifying a robust gene expression signature associated with hepatocyte differentiation and liver metabolism. In addition, the signature was able to distinguish specific developmental stages in mice. More importantly, the signature identified a subset of human HCC associated with a poor prognosis and cancer stem cell features. By using an independent HCC dataset (TCGA consortium), a minimal subset of seven differentiation-related genes was shown to predict a reduced overall survival, not only in patients with HCC but also in other types of cancers (e.g., kidney, pancreas, skin). In conclusion, the study identified a minimal subset of seven genes reflecting the differentiation status of tumor hepatocytes and clinically relevant for predicting the prognosis of HCC patients.Matthis DesoteuxCorentin LouisKevin BévantDenise GlaiseCédric CoulouarnMDPI AGarticlehepatocellular carcinomaprognosissignaturedifferentiationoverall survivalintegrative transcriptomicsNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5624, p 5624 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	hepatocellular carcinoma prognosis signature differentiation overall survival integrative transcriptomics Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	hepatocellular carcinoma prognosis signature differentiation overall survival integrative transcriptomics Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Matthis Desoteux Corentin Louis Kevin Bévant Denise Glaise Cédric Coulouarn A Minimal Subset of Seven Genes Associated with Tumor Hepatocyte Differentiation Predicts a Poor Prognosis in Human Hepatocellular Carcinoma
description	Hepatocellular carcinoma (HCC) is a deadly cancer worldwide as a result of a frequent late diagnosis which limits the therapeutic options. Tumor progression in HCC is closely correlated with the dedifferentiation of hepatocytes, the main parenchymal cells in the liver. Here, we hypothesized that the expression level of genes reflecting the differentiation status of tumor hepatocytes could be clinically relevant in defining subsets of patients with different clinical outcomes. To test this hypothesis, an integrative transcriptomics approach was used to stratify a cohort of 139 HCC patients based on a gene expression signature established in vitro in the HepaRG cell line using well-controlled culture conditions recapitulating tumor hepatocyte differentiation. The HepaRG model was first validated by identifying a robust gene expression signature associated with hepatocyte differentiation and liver metabolism. In addition, the signature was able to distinguish specific developmental stages in mice. More importantly, the signature identified a subset of human HCC associated with a poor prognosis and cancer stem cell features. By using an independent HCC dataset (TCGA consortium), a minimal subset of seven differentiation-related genes was shown to predict a reduced overall survival, not only in patients with HCC but also in other types of cancers (e.g., kidney, pancreas, skin). In conclusion, the study identified a minimal subset of seven genes reflecting the differentiation status of tumor hepatocytes and clinically relevant for predicting the prognosis of HCC patients.
format	article
author	Matthis Desoteux Corentin Louis Kevin Bévant Denise Glaise Cédric Coulouarn
author_facet	Matthis Desoteux Corentin Louis Kevin Bévant Denise Glaise Cédric Coulouarn
author_sort	Matthis Desoteux
title	A Minimal Subset of Seven Genes Associated with Tumor Hepatocyte Differentiation Predicts a Poor Prognosis in Human Hepatocellular Carcinoma
title_short	A Minimal Subset of Seven Genes Associated with Tumor Hepatocyte Differentiation Predicts a Poor Prognosis in Human Hepatocellular Carcinoma
title_full	A Minimal Subset of Seven Genes Associated with Tumor Hepatocyte Differentiation Predicts a Poor Prognosis in Human Hepatocellular Carcinoma
title_fullStr	A Minimal Subset of Seven Genes Associated with Tumor Hepatocyte Differentiation Predicts a Poor Prognosis in Human Hepatocellular Carcinoma
title_full_unstemmed	A Minimal Subset of Seven Genes Associated with Tumor Hepatocyte Differentiation Predicts a Poor Prognosis in Human Hepatocellular Carcinoma
title_sort	minimal subset of seven genes associated with tumor hepatocyte differentiation predicts a poor prognosis in human hepatocellular carcinoma
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/d7fa1cd5c2244985a5a60004b9d7a54f
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A Minimal Subset of Seven Genes Associated with Tumor Hepatocyte Differentiation Predicts a Poor Prognosis in Human Hepatocellular Carcinoma

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