Prognostic Significance of Tumor Mutation Burden among Patients with Non-small Cell Lung Cancer Who Received Platinum-based Adjuvant Chemotherapy: An Exploratory Study.

IF 2.5 Q3 ONCOLOGY
Wei-Xi Shen, Guang-Hua Li, Yu-Jia Li, Peng-Fei Zhang, Jia-Xing Yu, Di Shang, Qiu-Shi Wang
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Abstract

This study aimed to investigate the prognostic significance of tumor mutation burden (TMB) among patients with non-small cell lung cancer (NSCLC) who received platinum-based adjuvant chemotherapy. Tumor tissue specimens after surgical resection were collected for DNA extraction. Somatic mutation detection and TMB analysis were conducted using next-generation sequencing (NGS). Recurrence status of the patients was assessed in the hospital during the adjuvant chemotherapy period, and long-term survival data of patients were obtained by telephone follow-up. Univariate analysis between TMB status and prognosis was carried out by survival analysis. A retrospective review of 78 patients with non-squamous NSCLC who received platinum-based adjuvant chemotherapy showed a median disease-free survival of 3.6 years and median overall survival (OS) of 5.3 years. NGS analysis exhibited that the most common mutated somatic genes among the 78 patients were tumor suppressor protein p53 (TP53), epidermal growth factor receptor, low-density lipoprotein receptor related protein 1B, DNA methyltransferase 3 alpha and FAT atypical cadherin 3, and their prevalence was 56.4%, 48.7%, 37.2%, 30.7%, and 25.6%, respectively. TMB status was divided into TMB-L (≤ 4.5/Mb) and TMB-H (> 4.5/Mb) based on the median TMB threshold. Relevance of TMB to prognosis suggested that the median OS of patients with TMB-L was significantly longer than that of patients with TMB-H (NR vs. 4.6, P = 0.014). Higher TMB status conferred a worse implication on OS among patients with non-squamous NSCLC who received platinum-based adjuvant chemotherapy.

接受铂类辅助化疗的非小细胞肺癌患者肿瘤突变负担的预后意义:一项探索性研究
本研究旨在探讨接受铂类辅助化疗的非小细胞肺癌(NSCLC)患者中肿瘤突变负荷(TMB)的预后意义。采集手术切除后的肿瘤组织标本进行DNA提取。采用新一代测序技术(NGS)进行体细胞突变检测和TMB分析。辅助化疗期间在医院对患者的复发状况进行评估,并通过电话随访获得患者的长期生存数据。通过生存分析对 TMB 状态和预后进行单变量分析。一项对78例接受铂类辅助化疗的非鳞癌NSCLC患者的回顾性研究显示,患者的中位无病生存期为3.6年,中位总生存期(OS)为5.3年。NGS分析显示,78名患者中最常见的突变体细胞基因是肿瘤抑制蛋白p53(TP53)、表皮生长因子受体、低密度脂蛋白受体相关蛋白1B、DNA甲基转移酶3α和FAT非典型粘附蛋白3,其发生率分别为56.4%、48.7%、37.2%、30.7%和25.6%。根据TMB阈值的中位数,TMB状态分为TMB-L(≤ 4.5/Mb)和TMB-H(> 4.5/Mb)。TMB与预后的相关性表明,TMB-L患者的中位OS明显长于TMB-H患者(NR vs. 4.6,P = 0.014)。在接受铂类辅助化疗的非鳞NSCLC患者中,TMB状态越高,其OS越差。
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