Targeted Next-Generation Sequencing Analysis Predicts the Recurrence in Resected Lung Adenocarcinoma Harboring <i>EGFR</i> Mutations

• Main Authors: In Ae Kim, Jae Young Hur, Hee Joung Kim, Song Am Lee, Jae Joon Hwang, Wan Seop Kim, Kye Young Lee
• Format: Article
• Language: English
• Published: MDPI AG 2021-07-01
• Series: Cancers
• Subjects: targeted next-generation sequencing; resected <i>EGFR</i> mutated-lung adenocarcinoma; <i>CTNNB1</i>; post-operative recurrence; recurrence-free survival
• Online Access: https://www.mdpi.com/2072-6694/13/14/3632

Targeted NGS, widely applied to identify driver oncogenes in advanced lung adenocarcinoma, may also be applied to resected early stage cancers. We investigated resected <i>EGFR</i>-mutated lung adenocarcinoma mutation profiles to evaluate prognostic impacts. Tissues from 131 patients who had complete resection of stage I–IIIA <i>EGFR</i>-mutated lung adenocarcinoma were analyzed by targeted NGS for 207 cancer-related genes. Recurrence free survival (RFS) was estimated according to genetic alterations using the Kaplan–Meier method and Cox proportional regression analysis. The relapse rate was 25.2% (33/131). Five-year RFS of stages IA, IB, II, and IIIA were 82%, 75%, 35%, and 0%, respectively (<i>p</i> < 0.001). RFS decreased with the number of co-mutations (<i>p</i> = 0.025). Among co-mutations, the <i>CTNNB1</i> mutation was associated with short RFS in a multivariate analysis (hazard ratio: 5.4, 95% confidence interval: 2.1–14.4; <i>p</i> = 0.001). <i>TP53</i> mutations were associated with short RFS in stage IB–IIIA (<i>p</i> = 0.01). RFS was shorter with <i>EGFR</i> exon 19 deletion (19-del) than with mutation 21-L858R in stage IB–IIIA tumors (<i>p</i> = 0.008). Among 19-del subtypes, pL747_P753delinS (6/56, 8.9%) had shorter RFS than pE746_A750del (39/56, 69.6%), the most frequent subtype (<i>p</i> = 0.004).