Background: Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related mortality. This study investigates the clinical interest of whole exome sequencing (WES) for analyzing somatic mutational signatures in patients with advanced or metastatic NSCLC treated with the current standard of care. Methods: Exome sequencing data and clinical characteristics from 132 patients with advanced or metastatic NSCLC were analyzed. Somatic mutational signatures including single base substitutions (SBSs), double base substitutions (DBSs), and copy number signatures were evaluated. Structural variations including tumor mutational burden (TMB), the number of neoantigens, TCR clonality, homologous recombination deficiency (HRD), copy number alterations (CNAs), and microsatellite instability (MSI) score were determined. The association between these genomic features, NSCLC subtypes, and patient outcomes (progression-free and overall survival) was evaluated. Conclusions: Exome sequencing offers valuable insights into somatic mutational signatures in NSCLC. This study identified specific signatures associated with a poor response to immune checkpoint inhibitor (ICI) therapy and chemotherapy, potentially aiding treatment selection and identifying patients unlikely to benefit from these approaches.
背景：非小细胞肺癌（NSCLC）仍是癌症相关死亡的主要原因。本研究探讨了全外显子组测序（WES）在分析接受当前标准治疗的晚期或转移性NSCLC患者体细胞突变特征方面的临床价值。方法：本研究分析了132例晚期或转移性NSCLC患者的外显子组测序数据及临床特征，评估了包括单碱基替换（SBS）、双碱基替换（DBS）和拷贝数特征在内的体细胞突变特征，并测定了肿瘤突变负荷（TMB）、新抗原数量、TCR克隆性、同源重组缺陷（HRD）、拷贝数变异（CNA）和微卫星不稳定性（MSI）评分等结构变异指标。研究进一步评估了这些基因组特征与NSCLC亚型及患者预后（无进展生存期和总生存期）之间的关联。结论：外显子组测序为解析NSCLC体细胞突变特征提供了重要视角。本研究识别出与免疫检查点抑制剂（ICI）治疗及化疗反应不佳相关的特定特征，可能有助于指导治疗选择并识别无法从这些治疗方案中获益的患者群体。
肿瘤(癌症)患者之家