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Tumor mutation burden estimated by a 69-gene-panel is associated with overall survival in patients with diffuse large B-cell lymphoma
BACKGROUND: Tumor mutation burden (TMB) as estimated by cancer gene panels (CGPs) has been confirmed to be associated with prognosis and is effective in predicting clinical benefit from immune checkpoint blockade (ICB) in solid tumors. However, whether the TMB calculated by CGPs is associated with o...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7962318/ https://www.ncbi.nlm.nih.gov/pubmed/33722306 http://dx.doi.org/10.1186/s40164-021-00215-4 |
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author | Chen, Cunte Liu, Sichu Jiang, Xinmiao Huang, Ling Chen, Feili Wei, Xiaojun Guo, Hanguo Shao, Yang Li, Yangqiu Li, Wenyu |
author_facet | Chen, Cunte Liu, Sichu Jiang, Xinmiao Huang, Ling Chen, Feili Wei, Xiaojun Guo, Hanguo Shao, Yang Li, Yangqiu Li, Wenyu |
author_sort | Chen, Cunte |
collection | PubMed |
description | BACKGROUND: Tumor mutation burden (TMB) as estimated by cancer gene panels (CGPs) has been confirmed to be associated with prognosis and is effective in predicting clinical benefit from immune checkpoint blockade (ICB) in solid tumors. However, whether the TMB calculated by CGPs is associated with overall survival (OS) for patients with diffuse large B-cell lymphoma (DLBCL) is worth exploring. METHODS: The prognostic value of panel-TMB, calculated by a panel of 69 genes (GP69), for 87 DLBCL patients in our clinical center (GDPH dataset) was explored. The results were further validated using 37 DLBCL patients from the Cancer Genome Atlas (TCGA) database (TCGA dataset). RESULTS: Spearman correlation analysis suggested that panel-TMB is positively correlated with the TMB calculated by whole-exome sequencing (wTMB) in the TCGA dataset (R = 0.76, P < 0.0001). Both GDPH and TCGA results demonstrated that higher panel-TMB is significantly associated with a poor OS for DLBCL patients (P < 0.05) where a panel of 13 genes was associated with poor OS, and another panel of 26 genes was correlated with a favorable OS for DLBCL patients. Further subgroup analysis indicated that higher panel-TMB had shorter OS in DLBCL patients with younger than 60 years, elevated LDH, greater than one extranodal involvement, stage III/IV, an IPI score of 3–5, or HBsAg, anti-HBc, or HBV-DNA negativity (P < 0.05). Interestingly, the nomogram model constructed by panel-TMB, stage, and IPI could individually and visually predict the 1-, 2- and 3-year OS rates of DLBCL patients. CONCLUSIONS: We established GP69 for the evaluation of OS for Chinese DLBCL patients. panel-TMB might be a potential predictor for prognostic stratification of DLBCL patients. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40164-021-00215-4. |
format | Online Article Text |
id | pubmed-7962318 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-79623182021-03-16 Tumor mutation burden estimated by a 69-gene-panel is associated with overall survival in patients with diffuse large B-cell lymphoma Chen, Cunte Liu, Sichu Jiang, Xinmiao Huang, Ling Chen, Feili Wei, Xiaojun Guo, Hanguo Shao, Yang Li, Yangqiu Li, Wenyu Exp Hematol Oncol Research BACKGROUND: Tumor mutation burden (TMB) as estimated by cancer gene panels (CGPs) has been confirmed to be associated with prognosis and is effective in predicting clinical benefit from immune checkpoint blockade (ICB) in solid tumors. However, whether the TMB calculated by CGPs is associated with overall survival (OS) for patients with diffuse large B-cell lymphoma (DLBCL) is worth exploring. METHODS: The prognostic value of panel-TMB, calculated by a panel of 69 genes (GP69), for 87 DLBCL patients in our clinical center (GDPH dataset) was explored. The results were further validated using 37 DLBCL patients from the Cancer Genome Atlas (TCGA) database (TCGA dataset). RESULTS: Spearman correlation analysis suggested that panel-TMB is positively correlated with the TMB calculated by whole-exome sequencing (wTMB) in the TCGA dataset (R = 0.76, P < 0.0001). Both GDPH and TCGA results demonstrated that higher panel-TMB is significantly associated with a poor OS for DLBCL patients (P < 0.05) where a panel of 13 genes was associated with poor OS, and another panel of 26 genes was correlated with a favorable OS for DLBCL patients. Further subgroup analysis indicated that higher panel-TMB had shorter OS in DLBCL patients with younger than 60 years, elevated LDH, greater than one extranodal involvement, stage III/IV, an IPI score of 3–5, or HBsAg, anti-HBc, or HBV-DNA negativity (P < 0.05). Interestingly, the nomogram model constructed by panel-TMB, stage, and IPI could individually and visually predict the 1-, 2- and 3-year OS rates of DLBCL patients. CONCLUSIONS: We established GP69 for the evaluation of OS for Chinese DLBCL patients. panel-TMB might be a potential predictor for prognostic stratification of DLBCL patients. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40164-021-00215-4. BioMed Central 2021-03-15 /pmc/articles/PMC7962318/ /pubmed/33722306 http://dx.doi.org/10.1186/s40164-021-00215-4 Text en © The Author(s) 2021 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Chen, Cunte Liu, Sichu Jiang, Xinmiao Huang, Ling Chen, Feili Wei, Xiaojun Guo, Hanguo Shao, Yang Li, Yangqiu Li, Wenyu Tumor mutation burden estimated by a 69-gene-panel is associated with overall survival in patients with diffuse large B-cell lymphoma |
title | Tumor mutation burden estimated by a 69-gene-panel is associated with overall survival in patients with diffuse large B-cell lymphoma |
title_full | Tumor mutation burden estimated by a 69-gene-panel is associated with overall survival in patients with diffuse large B-cell lymphoma |
title_fullStr | Tumor mutation burden estimated by a 69-gene-panel is associated with overall survival in patients with diffuse large B-cell lymphoma |
title_full_unstemmed | Tumor mutation burden estimated by a 69-gene-panel is associated with overall survival in patients with diffuse large B-cell lymphoma |
title_short | Tumor mutation burden estimated by a 69-gene-panel is associated with overall survival in patients with diffuse large B-cell lymphoma |
title_sort | tumor mutation burden estimated by a 69-gene-panel is associated with overall survival in patients with diffuse large b-cell lymphoma |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7962318/ https://www.ncbi.nlm.nih.gov/pubmed/33722306 http://dx.doi.org/10.1186/s40164-021-00215-4 |
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