DNA修复基因及其TP53共突变在肺腺癌免疫治疗疗效预测中的价值  

Value of DNA Repair Gene and TP53 Co-mutation in Predicting Effect of Immunotherapy on Lung Adenocarcinoma

作　　者：陈广英 马俊勋 胡毅 Chen Guangying;Ma a Junxun;Hu Yi(Department of Oncology,The First Medical Center,Chinese PLA General Hospital,Beijing 100853,China;Medical School of Chinese PLA,Beijing 100853,China;Department of Oncology,The Fifth Medical Center,Chinese PLA General Hospital,Beijing 100071,China)

机构地区：[1]中国人民解放军总医院第一医学中心肿瘤内科,北京100853 [2]解放军医学院,北京100853 [3]中国人民解放军总医院第五医学中心肿瘤内科,北京100071

出　　处：《肿瘤防治研究》2021年第7期704-708,共5页Cancer Research on Prevention and Treatment

基　　金：中国博士后科学基金面上项目(45066)。

摘　　要：目的基于二代测序技术,探索DNA修复基因(DRGs)对肺腺癌免疫治疗疗效的预测价值。方法选取癌症基因组图谱中肺腺癌两个独立数据集(分别为测试集和验证集)。测试集中,依据肿瘤突变负荷评分15为阈值,分为低突变负荷组和高突变负荷组,分析不同肿瘤突变负荷与肺腺癌总生存的关系,并以KRAS/TP53共突变作为标准参照,分析DRGs突变及其与KRAS或者TP53的共突变,预测肿瘤突变数量及肿瘤突变负荷的效能。在验证集中分析DRGs突变及其共突变在肿瘤突变负荷、新生抗原以及无进展生存期等方面的差异。结果相比单纯TP53或DRGs突变组,TP53/DRGs共突变组具有更高的肿瘤突变数量和肿瘤突变负荷,差异有统计学意义(P<0.05);与标准参照KRAS/TP53共突变组相比,亦显示出更高的肿瘤突变数量和肿瘤突变负荷,差异均有统计学意义(P=0.037,P=0.044)。在验证集分析中,相比单纯TP53或DRG突变或KRAS/TP53共突变的患者,TP53/DRGs共突变组患者也显示出较高的肿瘤新生抗原、肿瘤突变负荷和更长的无进展生存期。结论TP53/DRGs共突变或许可以作为肺腺癌免疫治疗疗效预测的标志物。Objective To explore the value of DNA repair genes(DRGs)in predicting the effect of immunotherapy on lung adenocarcinoma based on second-generation sequencing technology.Methods The data of lung adenocarcinoma were obtained from the Cancer Genome Atlas,including the testing cohort and the validation cohort.In the testing set,according to the cut-off value of tumor mutational burden(TMB)score 15,the patients with lung adenocarcinoma were divided into two groups:the low TMB score group and the high TMB score group.And we analyzed the relation between TMB and the overall survival of lung adenocarcinoma patients.KRAS and TP53 co-mutation was used as the standard control,the differences in the mutation count and TMB score between only DRGs mutation group and KRAS or TP53 co-mutation groups were analyzed.In the validation cohort,the differences between DRGs and KRAS or TP53 co-mutation groups in TMB,tumor neoantigen burden and PFS were analyzed.Results The patients with TP53/DRGs co-mutation had higher mutation count and TMB score than those patients with only TP53 or DRGs mutation(P<0.05).The patients with TP53/DRGs co-mutation had higher mutation count and TMB score than those patients with KRAS/TP53 co-mutation(P=0.037,P=0.044).In validation cohort analysis,the TP53/DRGs co-mutation patients also showed higher tumor neoantigens,higher TMB and longer progression-free survival than those patients with only TP53 or DRGs or KRAS/TP53 co-mutation groups.Conclusion TP53/DRGs co-mutation may be served as a pair of potential biomarkers for predicting the efficacy of immunotherapy on lung adenocarcinoma.

关 键 词：DNA修复基因 肺腺癌 免疫治疗 分子标志物 

分 类 号：R734.2[医药卫生—肿瘤]