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Super-Enhancer–Associated nine-gene prognostic score model for prediction of survival in chronic lymphocytic leukemia patients

Chronic lymphocytic leukemia (CLL) is a type of highly heterogeneous mature B-cell malignancy with various disease courses. Although a multitude of prognostic markers in CLL have been reported, insights into the role of super-enhancer (SE)–related risk indicators in the occurrence and development of...

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Autores principales: Liang, Xue, Meng, Ye, Li, Cong, Liu, Linlin, Wang, Yangyang, Pu, Lianfang, Hu, Linhui, Li, Qian, Zhai, Zhimin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9521409/
https://www.ncbi.nlm.nih.gov/pubmed/36186463
http://dx.doi.org/10.3389/fgene.2022.1001364
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author Liang, Xue
Meng, Ye
Li, Cong
Liu, Linlin
Wang, Yangyang
Pu, Lianfang
Hu, Linhui
Li, Qian
Zhai, Zhimin
author_facet Liang, Xue
Meng, Ye
Li, Cong
Liu, Linlin
Wang, Yangyang
Pu, Lianfang
Hu, Linhui
Li, Qian
Zhai, Zhimin
author_sort Liang, Xue
collection PubMed
description Chronic lymphocytic leukemia (CLL) is a type of highly heterogeneous mature B-cell malignancy with various disease courses. Although a multitude of prognostic markers in CLL have been reported, insights into the role of super-enhancer (SE)–related risk indicators in the occurrence and development of CLL are still lacking. A super-enhancer (SE) is a cluster of enhancers involved in cell differentiation and tumorigenesis, and is one of the promising therapeutic targets for cancer therapy in recent years. In our study, the CLL-related super-enhancers in the training database were processed by LASSO-penalized Cox regression analysis to screen a nine-gene prognostic model including TCF7, VEGFA, MNT, GMIP, SLAMF1, TNFRSF25, GRWD1, SLC6AC, and LAG3. The SE-related risk score was further constructed and it was found that the predictive performance with overall survival and time-to-treatment (TTT) was satisfactory. Moreover, a high correlation was found between the risk score and already known prognostic markers of CLL. In the meantime, we noticed that the expressions of TCF7, GMIP, SLAMF1, TNFRSF25, and LAG3 in CLL were different from those of healthy donors (p < 0.01). Moreover, the risk score and LAG3 level of matched pairs before and after treatment samples varied significantly. Finally, an interactive nomogram consisting of the nine-gene risk group and four clinical traits was established. The inhibitors of mTOR and cyclin-dependent kinases (CDKs) were considered effective in patients in the high-risk group according to the pRRophetic algorithm. Collectively, the SE-associated nine-gene prognostic model developed here may be used to predict the prognosis and assist in the risk stratification and treatment of CLL patients in the future.
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spelling pubmed-95214092022-09-30 Super-Enhancer–Associated nine-gene prognostic score model for prediction of survival in chronic lymphocytic leukemia patients Liang, Xue Meng, Ye Li, Cong Liu, Linlin Wang, Yangyang Pu, Lianfang Hu, Linhui Li, Qian Zhai, Zhimin Front Genet Genetics Chronic lymphocytic leukemia (CLL) is a type of highly heterogeneous mature B-cell malignancy with various disease courses. Although a multitude of prognostic markers in CLL have been reported, insights into the role of super-enhancer (SE)–related risk indicators in the occurrence and development of CLL are still lacking. A super-enhancer (SE) is a cluster of enhancers involved in cell differentiation and tumorigenesis, and is one of the promising therapeutic targets for cancer therapy in recent years. In our study, the CLL-related super-enhancers in the training database were processed by LASSO-penalized Cox regression analysis to screen a nine-gene prognostic model including TCF7, VEGFA, MNT, GMIP, SLAMF1, TNFRSF25, GRWD1, SLC6AC, and LAG3. The SE-related risk score was further constructed and it was found that the predictive performance with overall survival and time-to-treatment (TTT) was satisfactory. Moreover, a high correlation was found between the risk score and already known prognostic markers of CLL. In the meantime, we noticed that the expressions of TCF7, GMIP, SLAMF1, TNFRSF25, and LAG3 in CLL were different from those of healthy donors (p < 0.01). Moreover, the risk score and LAG3 level of matched pairs before and after treatment samples varied significantly. Finally, an interactive nomogram consisting of the nine-gene risk group and four clinical traits was established. The inhibitors of mTOR and cyclin-dependent kinases (CDKs) were considered effective in patients in the high-risk group according to the pRRophetic algorithm. Collectively, the SE-associated nine-gene prognostic model developed here may be used to predict the prognosis and assist in the risk stratification and treatment of CLL patients in the future. Frontiers Media S.A. 2022-09-15 /pmc/articles/PMC9521409/ /pubmed/36186463 http://dx.doi.org/10.3389/fgene.2022.1001364 Text en Copyright © 2022 Liang, Meng, Li, Liu, Wang, Pu, Hu, Li and Zhai. 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 Genetics
Liang, Xue
Meng, Ye
Li, Cong
Liu, Linlin
Wang, Yangyang
Pu, Lianfang
Hu, Linhui
Li, Qian
Zhai, Zhimin
Super-Enhancer–Associated nine-gene prognostic score model for prediction of survival in chronic lymphocytic leukemia patients
title Super-Enhancer–Associated nine-gene prognostic score model for prediction of survival in chronic lymphocytic leukemia patients
title_full Super-Enhancer–Associated nine-gene prognostic score model for prediction of survival in chronic lymphocytic leukemia patients
title_fullStr Super-Enhancer–Associated nine-gene prognostic score model for prediction of survival in chronic lymphocytic leukemia patients
title_full_unstemmed Super-Enhancer–Associated nine-gene prognostic score model for prediction of survival in chronic lymphocytic leukemia patients
title_short Super-Enhancer–Associated nine-gene prognostic score model for prediction of survival in chronic lymphocytic leukemia patients
title_sort super-enhancer–associated nine-gene prognostic score model for prediction of survival in chronic lymphocytic leukemia patients
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9521409/
https://www.ncbi.nlm.nih.gov/pubmed/36186463
http://dx.doi.org/10.3389/fgene.2022.1001364
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