Development and validation of a new tumor-based gene signature predicting prognosis of HBV/HCV-included resected hepatocellular carcinoma patients
Abstract Background Due to the phenotypic and molecular diversity of hepatocellular carcinomas (HCC), it is still a challenge to determine patients’ prognosis. We aim to identify new prognostic markers for resected HCC patients. Methods 274 patients were retrospectively identified and samples collec...
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doaj-5d115c22976a4aba9fa3debf3537cd072020-11-25T03:11:47ZengBMCJournal of Translational Medicine1479-58762019-06-0117111310.1186/s12967-019-1946-8Development and validation of a new tumor-based gene signature predicting prognosis of HBV/HCV-included resected hepatocellular carcinoma patientsGui-Qi Zhu0Yi Yang1Er-Bao Chen2Biao Wang3Kun Xiao4Shi-Ming Shi5Zheng-Jun Zhou6Shao-Lai Zhou7Zheng Wang8Ying-Hong Shi9Jia Fan10Jian Zhou11Tian-Shu Liu12Zhi Dai13Liver Cancer Institute, Zhongshan Hospital, Fudan UniversityLiver Cancer Institute, Zhongshan Hospital, Fudan UniversityDepartment of Medical Oncology, Zhongshan Hospital, Fudan UniversityLiver Cancer Institute, Zhongshan Hospital, Fudan UniversityLiver Cancer Institute, Zhongshan Hospital, Fudan UniversityDepartment of Radiation Oncology, Zhongshan Hospital, Fudan UniversityLiver Cancer Institute, Zhongshan Hospital, Fudan UniversityLiver Cancer Institute, Zhongshan Hospital, Fudan UniversityLiver Cancer Institute, Zhongshan Hospital, Fudan UniversityLiver Cancer Institute, Zhongshan Hospital, Fudan UniversityLiver Cancer Institute, Zhongshan Hospital, Fudan UniversityLiver Cancer Institute, Zhongshan Hospital, Fudan UniversityDepartment of Medical Oncology, Zhongshan Hospital, Fudan UniversityLiver Cancer Institute, Zhongshan Hospital, Fudan UniversityAbstract Background Due to the phenotypic and molecular diversity of hepatocellular carcinomas (HCC), it is still a challenge to determine patients’ prognosis. We aim to identify new prognostic markers for resected HCC patients. Methods 274 patients were retrospectively identified and samples collected from Zhongshan hospital, Fudan University. We analyzed the gene expression patterns of tumors and compared expression patterns with patient survival times. We identified a “9-gene signature” associated with survival by using the coefficient and regression formula of multivariate Cox model. This molecular signature was then validated in three patients cohorts from internal cohort (n = 69), TCGA (n = 369) and GEO dataset (n = 80). Results We identified 9-gene signature consisting of ZC2HC1A, MARCKSL1, PTGS1, CDKN2B, CLEC10A, PRDX3, PRKCH, MPEG1 and LMO2. The 9-gene signature was used, combined with clinical parameters, to fit a multivariable Cox model to the training cohort (concordance index, ci = 0.85), which was successfully validated (ci = 0.86 for internal cohort; ci = 0.78 for in silico cohort). The signature showed improved performance compared with clinical parameters alone (ci = 0.70). Furthermore, the signature predicted patient prognosis than previous gene signatures more accurately. It was also used to stratify early-stage, HBV or HCV-infected patients into low and high-risk groups, leading to significant differences in survival in training and validation (P < 0.001). Conclusions The 9-gene signature, in which four were upregulated (ZC2HC1A, MARCKSL1, PTGS1, CDKN2B) and five (CLEC10A, PRDX3, PRKCH, MPEG1, LMO2) were downregulated in HCC with poor prognosis, stratified HCC patients into low and high risk group significantly in different clinical settings, including receiving adjuvant transarterial chemoembolization and especially in early stage disease. This new signature should be validated in prospective studies to stratify patients in clinical decisions.http://link.springer.com/article/10.1186/s12967-019-1946-8Hepatocellular carcinomaLiver resectionMolecular classificationMicroarray analysis |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Gui-Qi Zhu Yi Yang Er-Bao Chen Biao Wang Kun Xiao Shi-Ming Shi Zheng-Jun Zhou Shao-Lai Zhou Zheng Wang Ying-Hong Shi Jia Fan Jian Zhou Tian-Shu Liu Zhi Dai |
spellingShingle |
Gui-Qi Zhu Yi Yang Er-Bao Chen Biao Wang Kun Xiao Shi-Ming Shi Zheng-Jun Zhou Shao-Lai Zhou Zheng Wang Ying-Hong Shi Jia Fan Jian Zhou Tian-Shu Liu Zhi Dai Development and validation of a new tumor-based gene signature predicting prognosis of HBV/HCV-included resected hepatocellular carcinoma patients Journal of Translational Medicine Hepatocellular carcinoma Liver resection Molecular classification Microarray analysis |
author_facet |
Gui-Qi Zhu Yi Yang Er-Bao Chen Biao Wang Kun Xiao Shi-Ming Shi Zheng-Jun Zhou Shao-Lai Zhou Zheng Wang Ying-Hong Shi Jia Fan Jian Zhou Tian-Shu Liu Zhi Dai |
author_sort |
Gui-Qi Zhu |
title |
Development and validation of a new tumor-based gene signature predicting prognosis of HBV/HCV-included resected hepatocellular carcinoma patients |
title_short |
Development and validation of a new tumor-based gene signature predicting prognosis of HBV/HCV-included resected hepatocellular carcinoma patients |
title_full |
Development and validation of a new tumor-based gene signature predicting prognosis of HBV/HCV-included resected hepatocellular carcinoma patients |
title_fullStr |
Development and validation of a new tumor-based gene signature predicting prognosis of HBV/HCV-included resected hepatocellular carcinoma patients |
title_full_unstemmed |
Development and validation of a new tumor-based gene signature predicting prognosis of HBV/HCV-included resected hepatocellular carcinoma patients |
title_sort |
development and validation of a new tumor-based gene signature predicting prognosis of hbv/hcv-included resected hepatocellular carcinoma patients |
publisher |
BMC |
series |
Journal of Translational Medicine |
issn |
1479-5876 |
publishDate |
2019-06-01 |
description |
Abstract Background Due to the phenotypic and molecular diversity of hepatocellular carcinomas (HCC), it is still a challenge to determine patients’ prognosis. We aim to identify new prognostic markers for resected HCC patients. Methods 274 patients were retrospectively identified and samples collected from Zhongshan hospital, Fudan University. We analyzed the gene expression patterns of tumors and compared expression patterns with patient survival times. We identified a “9-gene signature” associated with survival by using the coefficient and regression formula of multivariate Cox model. This molecular signature was then validated in three patients cohorts from internal cohort (n = 69), TCGA (n = 369) and GEO dataset (n = 80). Results We identified 9-gene signature consisting of ZC2HC1A, MARCKSL1, PTGS1, CDKN2B, CLEC10A, PRDX3, PRKCH, MPEG1 and LMO2. The 9-gene signature was used, combined with clinical parameters, to fit a multivariable Cox model to the training cohort (concordance index, ci = 0.85), which was successfully validated (ci = 0.86 for internal cohort; ci = 0.78 for in silico cohort). The signature showed improved performance compared with clinical parameters alone (ci = 0.70). Furthermore, the signature predicted patient prognosis than previous gene signatures more accurately. It was also used to stratify early-stage, HBV or HCV-infected patients into low and high-risk groups, leading to significant differences in survival in training and validation (P < 0.001). Conclusions The 9-gene signature, in which four were upregulated (ZC2HC1A, MARCKSL1, PTGS1, CDKN2B) and five (CLEC10A, PRDX3, PRKCH, MPEG1, LMO2) were downregulated in HCC with poor prognosis, stratified HCC patients into low and high risk group significantly in different clinical settings, including receiving adjuvant transarterial chemoembolization and especially in early stage disease. This new signature should be validated in prospective studies to stratify patients in clinical decisions. |
topic |
Hepatocellular carcinoma Liver resection Molecular classification Microarray analysis |
url |
http://link.springer.com/article/10.1186/s12967-019-1946-8 |
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