Shen Wei-Xi, Li Guang-Hua, Li Yu-Jia, Zhang Peng-Fei, Yu Jia-Xing, Shang Di, Wang Qiu-Shi
Department of Oncology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
Department of Thoracic Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
J Cancer Prev. 2023 Dec 30;28(4):175-184. doi: 10.15430/JCP.2023.28.4.175.
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, = 0.014). Higher TMB status conferred a worse implication on OS among patients with non-squamous NSCLC who received platinum-based adjuvant chemotherapy.
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。收集手术切除后的肿瘤组织标本用于DNA提取。使用下一代测序(NGS)进行体细胞突变检测和TMB分析。在辅助化疗期间于医院评估患者的复发状态,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状态与预后进行单因素分析。对78例接受铂类辅助化疗的非鳞状NSCLC患者的回顾性研究显示,无病生存期的中位数为3.6年,总生存期(OS)的中位数为5.3年。NGS分析显示,这78例患者中最常见的体细胞突变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非典型钙黏蛋白3,其发生率分别为56.4%、48.7%、37.2%、30.7%和25.6%。根据TMB中位数阈值,将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OS中位数显著长于TMB-H患者(未达到 vs. 4.6,P = 0.014)。在接受铂类辅助化疗的非鳞状NSCLC患者中,较高的TMB状态对OS具有更差的影响。