Prognostic Model for the Risk Stratification of Early and Late Recurrence in Hepatitis B Virus-Related Small Hepatocellular Carcinoma Patients with Global Histone Modifications
Jin-Ling Duan,1,* Run-Cong Nie,1,2,* Zhi-Cheng Xiang,1,3,* Jie-Wei Chen,3 Min-Hua Deng,1,2 Hu Liang,1,4 Feng-Wei Wang,1 Rong-Zhen Luo,3 Dan Xie,1,3 Mu-Yan Cai1,3 1State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Cente...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Dove Medical Press
2021-05-01
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| Series: | Journal of Hepatocellular Carcinoma |
| Subjects: | |
| Online Access: | https://www.dovepress.com/prognostic-model-for-the-risk-stratification-of-early-and-late-recurre-peer-reviewed-fulltext-article-JHC |
| _version_ | 1818601607224360960 |
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| author | Duan JL Nie RC Xiang ZC Chen JW Deng MH Liang H Wang FW Luo RZ Xie D Cai MY |
| author_facet | Duan JL Nie RC Xiang ZC Chen JW Deng MH Liang H Wang FW Luo RZ Xie D Cai MY |
| author_sort | Duan JL |
| collection | DOAJ |
| description | Jin-Ling Duan,1,* Run-Cong Nie,1,2,* Zhi-Cheng Xiang,1,3,* Jie-Wei Chen,3 Min-Hua Deng,1,2 Hu Liang,1,4 Feng-Wei Wang,1 Rong-Zhen Luo,3 Dan Xie,1,3 Mu-Yan Cai1,3 1State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People’s Republic of China; 2Department of Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People’s Republic of China; 3Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People’s Republic of China; 4Department of Nasopharyngeal Carcinoma, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People’s Republic of China*These authors contributed equally to this workCorrespondence: Mu-Yan Cai; Dan XieState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People’s Republic of ChinaTel +86-20-87343193Fax +86-20-87343170Email caimy@sysucc.org.cn; xiedan@sysucc.org.cnBackground and Aim: To assess the profile of global histone modifications in small hepatocellular carcinoma (small HCC) and identify its prognostic value in predicting recurrence.Methods: The expression profiles of global histone modifications, including H2AK5AC, H2BK20AC, H3K4me2, H3K9AC, H3K18AC, H4K12AC, and H4R3me2, were evaluated with immunohistochemistry in 335 HBV related small HCC patients. Two histone signature classifiers were then developed using least absolute shrinkage and selection operator Cox regression. A nomogram was built using the classifier and independent risk factors. The performances of the classifier and nomogram were assessed by receiver operating characteristic curves.Results: Histone modifications were more pronounced in tumor tissues than in adjacent liver tissues. In tumor tissues, the risk score built based on the seven-histone signature exhibited satisfactory prediction efficiency, with an AUC = 0.71 (0.63– 0.79) for 2-year survival in the training cohort. Patients with a high risk score had shorter recurrence-free survival than those with a low risk score (HR: 1.96, 95% CI: 1.24– 3.08, p = 0.004; HR: 1.95, 95% CI: 1.12– 3.42, p = 0.019; and HR: 1.97, 95% CI: 1.39– 2.80, p < 0.001 for the training, validation and total cohorts, respectively). Furthermore, the statistical nomogram built using the histone classifier for early recurrence had a C-index = 0.68. In non-neoplastic liver tissues, the hepatic signature based on H3K4me2 and H4R3me2 was related to late recurrence (HR: 2.00, 95% CI: 1.15– 3.48, p = 0.01).Conclusion: Global histone modifications in tumor and adjacent liver tissues are novel predictors of early and late recurrence, respectively, in HBV-related small HCC patients.Keywords: small hepatocellular carcinoma, histone modifications, recurrence, LASSO, prognosis |
| first_indexed | 2024-12-16T12:54:04Z |
| format | Article |
| id | doaj.art-e500f3a44e5142f282a2d8f79477926b |
| institution | Directory Open Access Journal |
| issn | 2253-5969 |
| language | English |
| last_indexed | 2024-12-16T12:54:04Z |
| publishDate | 2021-05-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Journal of Hepatocellular Carcinoma |
| spelling | doaj.art-e500f3a44e5142f282a2d8f79477926b2022-12-21T22:31:05ZengDove Medical PressJournal of Hepatocellular Carcinoma2253-59692021-05-01Volume 849350565303Prognostic Model for the Risk Stratification of Early and Late Recurrence in Hepatitis B Virus-Related Small Hepatocellular Carcinoma Patients with Global Histone ModificationsDuan JLNie RCXiang ZCChen JWDeng MHLiang HWang FWLuo RZXie DCai MYJin-Ling Duan,1,* Run-Cong Nie,1,2,* Zhi-Cheng Xiang,1,3,* Jie-Wei Chen,3 Min-Hua Deng,1,2 Hu Liang,1,4 Feng-Wei Wang,1 Rong-Zhen Luo,3 Dan Xie,1,3 Mu-Yan Cai1,3 1State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People’s Republic of China; 2Department of Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People’s Republic of China; 3Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People’s Republic of China; 4Department of Nasopharyngeal Carcinoma, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People’s Republic of China*These authors contributed equally to this workCorrespondence: Mu-Yan Cai; Dan XieState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People’s Republic of ChinaTel +86-20-87343193Fax +86-20-87343170Email caimy@sysucc.org.cn; xiedan@sysucc.org.cnBackground and Aim: To assess the profile of global histone modifications in small hepatocellular carcinoma (small HCC) and identify its prognostic value in predicting recurrence.Methods: The expression profiles of global histone modifications, including H2AK5AC, H2BK20AC, H3K4me2, H3K9AC, H3K18AC, H4K12AC, and H4R3me2, were evaluated with immunohistochemistry in 335 HBV related small HCC patients. Two histone signature classifiers were then developed using least absolute shrinkage and selection operator Cox regression. A nomogram was built using the classifier and independent risk factors. The performances of the classifier and nomogram were assessed by receiver operating characteristic curves.Results: Histone modifications were more pronounced in tumor tissues than in adjacent liver tissues. In tumor tissues, the risk score built based on the seven-histone signature exhibited satisfactory prediction efficiency, with an AUC = 0.71 (0.63– 0.79) for 2-year survival in the training cohort. Patients with a high risk score had shorter recurrence-free survival than those with a low risk score (HR: 1.96, 95% CI: 1.24– 3.08, p = 0.004; HR: 1.95, 95% CI: 1.12– 3.42, p = 0.019; and HR: 1.97, 95% CI: 1.39– 2.80, p < 0.001 for the training, validation and total cohorts, respectively). Furthermore, the statistical nomogram built using the histone classifier for early recurrence had a C-index = 0.68. In non-neoplastic liver tissues, the hepatic signature based on H3K4me2 and H4R3me2 was related to late recurrence (HR: 2.00, 95% CI: 1.15– 3.48, p = 0.01).Conclusion: Global histone modifications in tumor and adjacent liver tissues are novel predictors of early and late recurrence, respectively, in HBV-related small HCC patients.Keywords: small hepatocellular carcinoma, histone modifications, recurrence, LASSO, prognosishttps://www.dovepress.com/prognostic-model-for-the-risk-stratification-of-early-and-late-recurre-peer-reviewed-fulltext-article-JHCsmall hepatocellular carcinomahistone modificationsrecurrencelassoprognosis |
| spellingShingle | Duan JL Nie RC Xiang ZC Chen JW Deng MH Liang H Wang FW Luo RZ Xie D Cai MY Prognostic Model for the Risk Stratification of Early and Late Recurrence in Hepatitis B Virus-Related Small Hepatocellular Carcinoma Patients with Global Histone Modifications Journal of Hepatocellular Carcinoma small hepatocellular carcinoma histone modifications recurrence lasso prognosis |
| title | Prognostic Model for the Risk Stratification of Early and Late Recurrence in Hepatitis B Virus-Related Small Hepatocellular Carcinoma Patients with Global Histone Modifications |
| title_full | Prognostic Model for the Risk Stratification of Early and Late Recurrence in Hepatitis B Virus-Related Small Hepatocellular Carcinoma Patients with Global Histone Modifications |
| title_fullStr | Prognostic Model for the Risk Stratification of Early and Late Recurrence in Hepatitis B Virus-Related Small Hepatocellular Carcinoma Patients with Global Histone Modifications |
| title_full_unstemmed | Prognostic Model for the Risk Stratification of Early and Late Recurrence in Hepatitis B Virus-Related Small Hepatocellular Carcinoma Patients with Global Histone Modifications |
| title_short | Prognostic Model for the Risk Stratification of Early and Late Recurrence in Hepatitis B Virus-Related Small Hepatocellular Carcinoma Patients with Global Histone Modifications |
| title_sort | prognostic model for the risk stratification of early and late recurrence in hepatitis b virus related small hepatocellular carcinoma patients with global histone modifications |
| topic | small hepatocellular carcinoma histone modifications recurrence lasso prognosis |
| url | https://www.dovepress.com/prognostic-model-for-the-risk-stratification-of-early-and-late-recurre-peer-reviewed-fulltext-article-JHC |
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