Spatiotemporal genomic analysis reveals distinct molecular features in recurrent stage I non-small cell lung cancers
Kezhong Chen, Airong Yang, David P. Carbone, Nnennaya Kanu, Ke Liu, Ruiru Wang, Yuntao Nie, Haifeng Shen, Jian Bai, Lin Wu, Hui Li, Yanbin Shi, Tony Mok, Jun Yu, Fan Yang, Shuangxiu Wu, Mariam Jamal‐Hanjani, Jun Wang
Abstract
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.