Chen Cunte, Liu Sichu, Jiang Xinmiao, Huang Ling, Chen Feili, Wei Xiaojun, Guo Hanguo, Shao Yang, Li Yangqiu, Li Wenyu
Institute of Hematology, School of Medicine, Key Laboratory for Regenerative Medicine of Ministry of Education, Jinan University, Guangzhou, China.
Department of Lymphoma, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, School of Medicine, South China University of Technology, Guangzhou, China.
Exp Hematol Oncol. 2021 Mar 15;10(1):20. doi: 10.1186/s40164-021-00215-4.
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.
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).
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.
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.
癌症基因检测板（CGP）评估的肿瘤突变负荷（TMB）已被证实与预后相关，并且在预测实体瘤患者接受免疫检查点阻断（ICB）治疗的临床获益方面有效。然而，CGP计算的TMB是否与弥漫性大B细胞淋巴瘤（DLBCL）患者的总生存期（OS）相关值得探索。
探讨了由69个基因组成的检测板（GP69）计算的检测板TMB对我们临床中心87例DLBCL患者（GDPH数据集）的预后价值。使用来自癌症基因组图谱（TCGA）数据库的37例DLBCL患者（TCGA数据集）进一步验证结果。
Spearman相关性分析表明，检测板TMB与TCGA数据集中通过全外显子测序（wTMB）计算的TMB呈正相关（R = 0.76，P < 0.0001）。GDPH和TCGA的结果均表明，较高的检测板TMB与DLBCL患者较差的OS显著相关（P < 0.05），其中一组13个基因与较差的OS相关，另一组26个基因与DLBCL患者较好的OS相关。进一步的亚组分析表明，在年龄小于60岁、乳酸脱氢酶升高、结外受累超过一处、III/IV期、国际预后指数（IPI）评分为3 - 5或乙肝表面抗原、乙肝核心抗体或乙肝病毒DNA阴性的DLBCL患者中，较高的检测板TMB的OS较短（P < 0.05）。有趣的是，由检测板TMB、分期和IPI构建的列线图模型可以单独且直观地预测DLBCL患者的1年、2年和3年OS率。
我们建立了GP69用于评估中国DLBCL患者的OS。检测板TMB可能是DLBCL患者预后分层的潜在预测指标。
