Thoracic Oncology Institute and Department of Thoracic Surgery, Peking University People's Hospital, Beijing 100044, China; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
Berry Oncology Corporation, Beijing 100102, China.
Cell Rep. 2022 Jul 12;40(2):111047. doi: 10.1016/j.celrep.2022.111047.
Stage I non-small cell lung cancer (NSCLC) presents diverse outcomes. To identify molecular features leading to tumor recurrence in early-stage NSCLC, we perform multiregional whole-exome sequencing (WES), RNA sequencing, and plasma-targeted circulating tumor DNA (ctDNA) detection analysis between recurrent and recurrent-free stage I NSCLC patients (CHN-P cohort) who had undergone R0 resection with a median 5-year follow-up time. Integrated analysis indicates that the multidimensional clinical and genomic model can stratify the prognosis of stage I NSCLC in both CHN-P and EUR-T cohorts and correlates with positive pre-surgical deep next generation sequencing (NGS) ctDNA detection. Increased genomic instability related to DNA interstrand crosslinks and double-strand break repair processes is significantly associated with early tumor relapse. This study reveals important molecular insights into stage I NSCLC and may inform clinical postoperative treatment and follow-up strategies.
I 期非小细胞肺癌（NSCLC）呈现出不同的结局。为了确定导致早期 NSCLC 肿瘤复发的分子特征，我们对接受 R0 切除且中位随访时间为 5 年的复发和无复发 I 期 NSCLC 患者（CHN-P 队列）进行了多区域全外显子组测序（WES）、RNA 测序和血浆靶向循环肿瘤 DNA（ctDNA）检测分析。综合分析表明，多维临床和基因组模型可以对 CHN-P 和 EUR-T 队列中的 I 期 NSCLC 进行分层，与术前深度下一代测序（NGS）ctDNA 检测阳性相关。与 DNA 链间交联和双链断裂修复过程相关的基因组不稳定性增加与早期肿瘤复发显著相关。这项研究揭示了 I 期 NSCLC 的重要分子见解，并可能为临床术后治疗和随访策略提供信息。
