Targeted Next-Generation Sequencing Analysis for Recurrence in Early-Stage Lung Adenocarcinoma

Background Despite surgical resection, early lung adenocarcinoma has a recurrence rate of 20–50%. No clear predictive markers for recurrence of early lung adenocarcinoma are available. Targeted next-generation sequencing (NGS) is rarely used to identify recurrence-related genes. We aimed to identify...

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Bibliographic Details
Published in:Annals of surgical oncology 2021-07, Vol.28 (7), p.3983-3993
Main Authors: Kim, In Ae, Hur, Jae Young, Kim, Hee Joung, Park, Jung Hoon, Hwang, Jae Joon, Lee, Song Am, Lee, Seung Eun, Kim, Wan Seop, Lee, Kye Young
Format: Article
Language:English
Subjects:
Adenocarcinoma
Adenocarcinoma of Lung - genetics
Epidermal growth factor receptors
High-Throughput Nucleotide Sequencing
Humans
Lung cancer
Lung Neoplasms - genetics
Lungs
Medical prognosis
Medicine
Medicine & Public Health
Multivariate analysis
Mutation
Neoplasm Recurrence, Local - genetics
Neoplasm Recurrence, Local - surgery
Next-generation sequencing
Oncology
p53 Protein
Prognosis
Sequence analysis
Surgery
Surgical Oncology
Translational Research
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Summary:Background Despite surgical resection, early lung adenocarcinoma has a recurrence rate of 20–50%. No clear predictive markers for recurrence of early lung adenocarcinoma are available. Targeted next-generation sequencing (NGS) is rarely used to identify recurrence-related genes. We aimed to identify genetic alterations that can predict recurrence, by comparing the molecular profiles of patient groups with and without recurrence. Methods Tissues from 230 patients with resected stage I–II lung adenocarcinoma (median follow-up: 49 months) were analyzed via targeted NGS for 207 cancer-related genes. The recurrence-free survival according to the number and type of mutation was estimated using the Kaplan–Meier method. Independent predictive biomarkers related to recurrence were identified using the Cox proportional hazards model. Results Recurrence was observed in 64 patients (27.8%). In multivariate analysis adjusted for age, sex, smoking history, stage, surgical mode, and visceral pleural invasion, the CTNNB1 mutation and fusion genes (ALK, ROS1, RET) were negative prognostic factors for recurrence in early-stage lung adenocarcinoma (HR 4.47, p  = 0.001; HR 2.73, p  = 0.009). EGFR mutation was a favorable factor (HR 0.51, p  = 0.016), but the CTNNB1/EGFR co-mutations were negative predictors (HR 19.2, p  
ISSN:1068-9265
1534-4681
DOI:10.1245/s10434-020-09276-x