A proportion of shared mutations in lung squamous cell carcinoma provides insights that may guide therapeutic approaches

Lung squamous cell carcinoma (LUSC) frequently arises within a genetically altered epithelium, yet the clinical significance of the cancerized field remains unclear.To investigate its biological and prognostic significance, we performed whole-exome and transcriptome analyses on precancer, primary tumor tissues, and their matched normal tissues from 76 LUSC patients. We defined the proportion of shared mutations (PSM) between precancer and corresponding tumor samples, which negatively correlates with poor recurrence-free survival and overall survival. Interestingly, high PSM was associated with early chromosomal instability, tobacco-related mutational signatures, and upregulation of metabolic and proliferative genes such as RRM2 and TIMMDC1 . Furthermore, molecular features of RRM2 and TIMMDC1 were enriched in the independent non-recurrence group. Additionally, copy number variations and gene expression patterns differed significantly between the PSM-low and PSM-high groups, suggesting the presence of clonal evolution within a cancerized field. These results demonstrate that PSM serves as a novel biomarker for prognosis and reveals key early events in the progression of LUSC. This study was supported by a grant (RS-2022-NR-071926 and RS-2018-NR031072) from the National Research Foundation of Korea (NRF).