Spatiotemporal genomic analysis reveals distinct molecular features in recurrent stage I non-small cell lung cancers

Cell Rep. 2022 Jul 12;40(2):111047. doi: 10.1016/j.celrep.2022.111047.

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.

Keywords: CP: cancer; DNA damage repair; circulating tumor DNA; disease-free survival; early stage; genome instability; genomic; heterogeneity; multiregion; non-small cell lung cancer; surgery.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / genetics
  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Carcinoma, Non-Small-Cell Lung* / pathology
  • Circulating Tumor DNA* / genetics
  • Genomics
  • High-Throughput Nucleotide Sequencing / methods
  • Humans
  • Lung Neoplasms* / pathology
  • Mutation
  • Neoplasm Recurrence, Local / genetics

Substances

  • Biomarkers, Tumor
  • Circulating Tumor DNA