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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...

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Autores principales: Zhang, Yuyuan, Liu, Zaoqu, Li, Xin, Liu, Long, Wang, Libo, Han, Xinwei, Li, Zhen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
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.
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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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