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The clinical implications of G1-G6 transcriptomic signature and 5-gene score in Korean patients with hepatocellular carcinoma

BACKGROUND: Efforts have been made to classify Hepatocellular Carcinoma (HCC) at surgically curable stages because molecular classification, which is prognostically informative, can accurately identify patients in need of additional early therapeutic interventions. Recently, HCC classification based...

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Autores principales: Ahn, Sung-Min, Haq, Farhan, Park, Inkeun, Nault, Jean-Charles, Zucman-Rossi, Jessica, Yu, Eunsil
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5960090/
https://www.ncbi.nlm.nih.gov/pubmed/29776391
http://dx.doi.org/10.1186/s12885-018-4192-1
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author Ahn, Sung-Min
Haq, Farhan
Park, Inkeun
Nault, Jean-Charles
Zucman-Rossi, Jessica
Yu, Eunsil
author_facet Ahn, Sung-Min
Haq, Farhan
Park, Inkeun
Nault, Jean-Charles
Zucman-Rossi, Jessica
Yu, Eunsil
author_sort Ahn, Sung-Min
collection PubMed
description BACKGROUND: Efforts have been made to classify Hepatocellular Carcinoma (HCC) at surgically curable stages because molecular classification, which is prognostically informative, can accurately identify patients in need of additional early therapeutic interventions. Recently, HCC classification based French studies on the expression of 16 genes and 5 genes were proposed. In 16-gene classification, transcriptomic signatures (G1-G6) were used to classify HCC patients into clinical, genomic and pathway-specific subgroups. In 5-gene score classification, the good or poor prognosis of HCC patients was predicted. The patient’s cohort in these studies was mainly from Caucasian and African populations. Here, we aimed to validate G1-G6 and 5-gene score signatures in 205 Korean HCC patients since genomic profiles of Korean patients are distinct from other regions. METHODS: Integrated analyses using whole-exome sequencing, copy number variation and clinical data was performed against these two signatures to find statistical correlations. Kaplan-Meier, univariate and multivariate COX regression analysis were performed for Disease-Specific Survival (DSS) and Recurrence-Free Survival (RFS). RESULTS: The G2 and G3 subgroups of transcriptomic signature were significantly associated with TP53 mutations while G5 and G6 subgroups were significantly associated with CTNNB1 mutations which is in concordance with original French studies. Similarly, the poor prognosis group of 5-gene score showed shorter DSS (p = 0.045) and early RFS (p = 0.023) as well as a significant association with microvascular invasion, tumor size (> 5 cm), elevated AFP levels, and RB1 mutations. However, the 5-gene score was not an independent prognostic factor for survival. CONCLUSION: The G1-G6 and 5-gene signatures showed significant concordance between genetic profiles of Korean HCC patients and patients in original French studies. Thus, G1-G6 and 5-gene score signatures can be targeted as potential therapeutic biomarkers against HCC patients worldwide.
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spelling pubmed-59600902018-05-24 The clinical implications of G1-G6 transcriptomic signature and 5-gene score in Korean patients with hepatocellular carcinoma Ahn, Sung-Min Haq, Farhan Park, Inkeun Nault, Jean-Charles Zucman-Rossi, Jessica Yu, Eunsil BMC Cancer Research Article BACKGROUND: Efforts have been made to classify Hepatocellular Carcinoma (HCC) at surgically curable stages because molecular classification, which is prognostically informative, can accurately identify patients in need of additional early therapeutic interventions. Recently, HCC classification based French studies on the expression of 16 genes and 5 genes were proposed. In 16-gene classification, transcriptomic signatures (G1-G6) were used to classify HCC patients into clinical, genomic and pathway-specific subgroups. In 5-gene score classification, the good or poor prognosis of HCC patients was predicted. The patient’s cohort in these studies was mainly from Caucasian and African populations. Here, we aimed to validate G1-G6 and 5-gene score signatures in 205 Korean HCC patients since genomic profiles of Korean patients are distinct from other regions. METHODS: Integrated analyses using whole-exome sequencing, copy number variation and clinical data was performed against these two signatures to find statistical correlations. Kaplan-Meier, univariate and multivariate COX regression analysis were performed for Disease-Specific Survival (DSS) and Recurrence-Free Survival (RFS). RESULTS: The G2 and G3 subgroups of transcriptomic signature were significantly associated with TP53 mutations while G5 and G6 subgroups were significantly associated with CTNNB1 mutations which is in concordance with original French studies. Similarly, the poor prognosis group of 5-gene score showed shorter DSS (p = 0.045) and early RFS (p = 0.023) as well as a significant association with microvascular invasion, tumor size (> 5 cm), elevated AFP levels, and RB1 mutations. However, the 5-gene score was not an independent prognostic factor for survival. CONCLUSION: The G1-G6 and 5-gene signatures showed significant concordance between genetic profiles of Korean HCC patients and patients in original French studies. Thus, G1-G6 and 5-gene score signatures can be targeted as potential therapeutic biomarkers against HCC patients worldwide. BioMed Central 2018-05-18 /pmc/articles/PMC5960090/ /pubmed/29776391 http://dx.doi.org/10.1186/s12885-018-4192-1 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Ahn, Sung-Min
Haq, Farhan
Park, Inkeun
Nault, Jean-Charles
Zucman-Rossi, Jessica
Yu, Eunsil
The clinical implications of G1-G6 transcriptomic signature and 5-gene score in Korean patients with hepatocellular carcinoma
title The clinical implications of G1-G6 transcriptomic signature and 5-gene score in Korean patients with hepatocellular carcinoma
title_full The clinical implications of G1-G6 transcriptomic signature and 5-gene score in Korean patients with hepatocellular carcinoma
title_fullStr The clinical implications of G1-G6 transcriptomic signature and 5-gene score in Korean patients with hepatocellular carcinoma
title_full_unstemmed The clinical implications of G1-G6 transcriptomic signature and 5-gene score in Korean patients with hepatocellular carcinoma
title_short The clinical implications of G1-G6 transcriptomic signature and 5-gene score in Korean patients with hepatocellular carcinoma
title_sort clinical implications of g1-g6 transcriptomic signature and 5-gene score in korean patients with hepatocellular carcinoma
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5960090/
https://www.ncbi.nlm.nih.gov/pubmed/29776391
http://dx.doi.org/10.1186/s12885-018-4192-1
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