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Comprehensive Molecular Analyses of a Six-Gene Signature for Predicting Late Recurrence of Hepatocellular Carcinoma
A larger number of patients with stages I–III hepatocellular carcinoma (HCC) experience late recurrence (LR) after surgery. We sought to develop a novel tool to stratify patients with different LR risk for tailoring decision-making for postoperative recurrence surveillance and therapy modalities. We...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8459683/ https://www.ncbi.nlm.nih.gov/pubmed/34568069 http://dx.doi.org/10.3389/fonc.2021.732447 |
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author | Zhang, Yuyuan Liu, Zaoqu Li, Xin Liu, Long Wang, Libo Han, Xinwei Li, Zhen |
author_facet | Zhang, Yuyuan Liu, Zaoqu Li, Xin Liu, Long Wang, Libo Han, Xinwei Li, Zhen |
author_sort | Zhang, Yuyuan |
collection | PubMed |
description | A larger number of patients with stages I–III hepatocellular carcinoma (HCC) experience late recurrence (LR) after surgery. We sought to develop a novel tool to stratify patients with different LR risk for tailoring decision-making for postoperative recurrence surveillance and therapy modalities. We retrospectively enrolled two independent public cohorts and 103 HCC tissues. Using LASSO logical analysis, a six-gene model was developed in the The Cancer Genome Atlas liver hepatocellular carcinoma (TCGA-LIHC) and independently validated in GSE76427. Further experimental validation using qRT-PCR assays was performed to ensure the robustness and clinical feasible of this signature. We developed a novel LR-related signature consisting of six genes. This signature was validated to be significantly associated with dismal recurrence-free survival in three cohorts TCGA-LIHC, GSE76427, and qPCR assays [HR: 2.007 (1.200–3.357), p = 0.008; HR: 2.171 (1.068, 4.412), p-value = 0.032; HR: 3.383 (2.100, 5.450), p-value <0.001]. More importantly, this signature displayed robust discrimination in predicting the LR risk, with AUCs being 0.73 (TCGA-LIHC), 0.93 (GSE76427), and 0.85 (in-house cohort). Furthermore, we deciphered the specific landscape of molecular alterations among patients in nonrecurrence (NR) and LR group to analyze the mechanism contributing to LR. For high-risk group, we also identified several potential drugs with specific sensitivity to high- and low-risk groups, which is vital to improve prognosis of LR-HCC after surgery. We discovered and experimentally validated a novel gene signature with powerful performance for identifying patients at high LR risk in stages I–III HCC. |
format | Online Article Text |
id | pubmed-8459683 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-84596832021-09-24 Comprehensive Molecular Analyses of a Six-Gene Signature for Predicting Late Recurrence of Hepatocellular Carcinoma Zhang, Yuyuan Liu, Zaoqu Li, Xin Liu, Long Wang, Libo Han, Xinwei Li, Zhen Front Oncol Oncology A larger number of patients with stages I–III hepatocellular carcinoma (HCC) experience late recurrence (LR) after surgery. We sought to develop a novel tool to stratify patients with different LR risk for tailoring decision-making for postoperative recurrence surveillance and therapy modalities. We retrospectively enrolled two independent public cohorts and 103 HCC tissues. Using LASSO logical analysis, a six-gene model was developed in the The Cancer Genome Atlas liver hepatocellular carcinoma (TCGA-LIHC) and independently validated in GSE76427. Further experimental validation using qRT-PCR assays was performed to ensure the robustness and clinical feasible of this signature. We developed a novel LR-related signature consisting of six genes. This signature was validated to be significantly associated with dismal recurrence-free survival in three cohorts TCGA-LIHC, GSE76427, and qPCR assays [HR: 2.007 (1.200–3.357), p = 0.008; HR: 2.171 (1.068, 4.412), p-value = 0.032; HR: 3.383 (2.100, 5.450), p-value <0.001]. More importantly, this signature displayed robust discrimination in predicting the LR risk, with AUCs being 0.73 (TCGA-LIHC), 0.93 (GSE76427), and 0.85 (in-house cohort). Furthermore, we deciphered the specific landscape of molecular alterations among patients in nonrecurrence (NR) and LR group to analyze the mechanism contributing to LR. For high-risk group, we also identified several potential drugs with specific sensitivity to high- and low-risk groups, which is vital to improve prognosis of LR-HCC after surgery. We discovered and experimentally validated a novel gene signature with powerful performance for identifying patients at high LR risk in stages I–III HCC. Frontiers Media S.A. 2021-09-09 /pmc/articles/PMC8459683/ /pubmed/34568069 http://dx.doi.org/10.3389/fonc.2021.732447 Text en Copyright © 2021 Zhang, Liu, Li, Liu, Wang, Han and Li https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Zhang, Yuyuan Liu, Zaoqu Li, Xin Liu, Long Wang, Libo Han, Xinwei Li, Zhen Comprehensive Molecular Analyses of a Six-Gene Signature for Predicting Late Recurrence of Hepatocellular Carcinoma |
title | Comprehensive Molecular Analyses of a Six-Gene Signature for Predicting Late Recurrence of Hepatocellular Carcinoma |
title_full | Comprehensive Molecular Analyses of a Six-Gene Signature for Predicting Late Recurrence of Hepatocellular Carcinoma |
title_fullStr | Comprehensive Molecular Analyses of a Six-Gene Signature for Predicting Late Recurrence of Hepatocellular Carcinoma |
title_full_unstemmed | Comprehensive Molecular Analyses of a Six-Gene Signature for Predicting Late Recurrence of Hepatocellular Carcinoma |
title_short | Comprehensive Molecular Analyses of a Six-Gene Signature for Predicting Late Recurrence of Hepatocellular Carcinoma |
title_sort | comprehensive molecular analyses of a six-gene signature for predicting late recurrence of hepatocellular carcinoma |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8459683/ https://www.ncbi.nlm.nih.gov/pubmed/34568069 http://dx.doi.org/10.3389/fonc.2021.732447 |
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