<p>Molecular Analysis of Oncogenic Mutations in Resected Margins by Next-Generation Sequencing Predicts Relapse in Non-Small Cell Lung Cancer Patients</p>

Abstract

Objective: To investigate the genetic mutations in both tumor and marginal tissues in patients with non-small cell lung cancer (NSCLC), and to evaluate the potential prognostic value in patients with margins gene positive. Methods: Next-generation sequencing (NGS) technique was used to detect genetic mutation in tumor and marginal tissues of the bronchus in 88 patients with NSCLC. Correlation of genetic mutations with pathology, lymph node metastasis, disease-free survival and overall survival was analyzed. Results: Of the 88 patients, 83 cases (94.3%) had gene mutations in the tumor samples and 12 cases (13.6%) had genetic alterations in their margins. Most of the gene mutations detected were cancer drivers. Six common driver genes between tumor and marginal tissues were identified, including EGFR, TP53, CDKN2A, CTNNB1, BRAF, and NF1. Kaplan-Meier analysis revealed that the median disease-free survival (DFS) was significantly shorter in patients with detectable gene mutations in marginal tissues compared with patients without mutations in margins (30.7 versus 24.4 months, log-rank χ 2 = 4.78, P =0.029). Consistently, a shorter median OS was observed in patients harboring gene mutations in margins compared with patients with no mutations in margins (49.1 versus 32.2 months, log-rank χ 2 = 3.669, P =0.055). Conclusion: These findings identify the presence of oncogenic alterations in microscopically negative margins in NSCLC patients associated with elevated risk of relapse and shorter survival time. Thus, examination of microscopically negative margins by NGS represents a valuable approach to predict the clinical outcome of NSCLC patients.

Recurrence/prognosis estimation using a molecularly positive surgical margin‐based model calls for alternative curative strategies in pIIIA/N2 NSCLC

“…[ 47 ] found that nearly 53% of the pancreatic cancer patients had detectable KRAS mutations in their H&E‐negative surgical margins samples, and these pancreatic cancer patients who were positive for surgical margins by the PCR‐based approach had a worse prognosis. Several gene mutations and DNA promoter hypermethylation changes were also successfully found in the surgical margins of NSCLC [ 48 , 49 ]. However, these studies had limited cohort size, utilized single gene sequencing data, or mainly focused on stage I‐II patients.…”

The Potential and Emerging Role of Quantitative Imaging Biomarkers for Cancer Characterization

“…The omics methodologies have been applied to a broad range of diseases. As some examples, survival in lung adenocarcinoma can be predicted by methylation signature [ 23 ], survival in patients with cancer of unknown primary can be improved with the use of whole-genome sequencing for therapy selection [ 24 ], and relapse in non-small lung cell cancer can be predicted by analyses of oncogenic mutations [ 25 ]. Via the combination of the different omics analyses, multi-omics analyses were established, making it possible to measure the different levels (e.g., mutational (genomics) and/or DNA methylation (epigenomics)) at which a pathway is affected.…”