Tumor mutation burden estimated by a 69-gene-panel is associated with overall survival in patients with diffuse large B-cell lymphoma
Abstract 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 associate...
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| Format: | Article |
| Language: | English |
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BMC
2021-03-01
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| Series: | Experimental Hematology & Oncology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40164-021-00215-4 |
| _version_ | 1819119928797560832 |
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| author | Cunte Chen Sichu Liu Xinmiao Jiang Ling Huang Feili Chen Xiaojun Wei Hanguo Guo Yang Shao Yangqiu Li Wenyu Li |
| author_facet | Cunte Chen Sichu Liu Xinmiao Jiang Ling Huang Feili Chen Xiaojun Wei Hanguo Guo Yang Shao Yangqiu Li Wenyu Li |
| author_sort | Cunte Chen |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-22T06:12:34Z |
| format | Article |
| id | doaj.art-534ed6599fe44536ad68e5219fc195b9 |
| institution | Directory Open Access Journal |
| issn | 2162-3619 |
| language | English |
| last_indexed | 2024-12-22T06:12:34Z |
| publishDate | 2021-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Experimental Hematology & Oncology |
| spelling | doaj.art-534ed6599fe44536ad68e5219fc195b92022-12-21T18:36:11ZengBMCExperimental Hematology & Oncology2162-36192021-03-0110111110.1186/s40164-021-00215-4Tumor mutation burden estimated by a 69-gene-panel is associated with overall survival in patients with diffuse large B-cell lymphomaCunte Chen0Sichu Liu1Xinmiao Jiang2Ling Huang3Feili Chen4Xiaojun Wei5Hanguo Guo6Yang Shao7Yangqiu Li8Wenyu Li9Institute of Hematology, School of Medicine, Key Laboratory for Regenerative Medicine of Ministry of Education, Jinan UniversityDepartment of Lymphoma, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, School of Medicine, South China University of TechnologyDepartment of Lymphoma, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, School of Medicine, South China University of TechnologyDepartment of Lymphoma, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, School of Medicine, South China University of TechnologyDepartment of Lymphoma, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, School of Medicine, South China University of TechnologyDepartment of Lymphoma, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, School of Medicine, South China University of TechnologyDepartment of Lymphoma, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, School of Medicine, South China University of TechnologyNanjing Geneseq Technology IncInstitute of Hematology, School of Medicine, Key Laboratory for Regenerative Medicine of Ministry of Education, Jinan UniversityDepartment of Lymphoma, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, School of Medicine, South China University of TechnologyAbstract 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.https://doi.org/10.1186/s40164-021-00215-4TMBGene panelPrognosisBiomarkerDiffuse large B-cell lymphoma |
| spellingShingle | Cunte Chen Sichu Liu Xinmiao Jiang Ling Huang Feili Chen Xiaojun Wei Hanguo Guo Yang Shao Yangqiu Li Wenyu Li Tumor mutation burden estimated by a 69-gene-panel is associated with overall survival in patients with diffuse large B-cell lymphoma Experimental Hematology & Oncology TMB Gene panel Prognosis Biomarker 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 | TMB Gene panel Prognosis Biomarker Diffuse large B-cell lymphoma |
| url | https://doi.org/10.1186/s40164-021-00215-4 |
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