Clinical, Genomic, and Transcriptomic Featurses of Lung Adenocarcinoma With Uncommon EGFR Mutation

Kazuki Hayasaka; Haruna Takeda; Akira Sakurada; Yuki Matsumura; Jiro Abe; Satoshi Shiono; Hirotsugu Notsuda; Hiroyuki Suzuki; Makoto Endo; Hozumi Motohashi; Yoshinori Okada

doi:10.1016/j.cllc.2023.10.006

Clinical, Genomic, and Transcriptomic Featurses of Lung Adenocarcinoma With Uncommon EGFR Mutation

Clin Lung Cancer. 2024 Jan;25(1):e43-e51. doi: 10.1016/j.cllc.2023.10.006. Epub 2023 Oct 18.

Authors

Affiliations

¹ Department of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan; Department of Gene Expression Regulation, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
² Department of Gene Expression Regulation, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
³ Department of Thoracic Surgery, South Miyagi Medical Center, Ogawara, Japan. Electronic address: akira.sakurada@gmail.com.
⁴ Department of Chest Surgery, Fukushima Medical University, Fukushima, Japan.
⁵ Department of Thoracic Surgery, Miyagi Cancer Center, Natori, Japan.
⁶ Department of Surgery II, Faculty of Medicine, Yamagata University, Yamagata, Japan.
⁷ Department of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
⁸ Department of Thoracic Surgery, Yamagata Prefectural Central Hospital, Yamagata, Japan.

PMID: 37985312
DOI: 10.1016/j.cllc.2023.10.006

Abstract

Purpose: The purpose of this study is to identify the clinical, genomic, and transcriptomic features of patients with lung adenocarcinoma (LUAD) harboring uncommon epidermal growth factor receptor (EGFR) mutations (UCM) compared with common EGFR mutations (CM).

Materials and methods: In this multicenter retrospective cohort study, clinicopathological data were collected from 1047 consecutive patients who underwent complete surgical resection for LUAD, as well as EGFR mutation analysis, between 2005 and 2012 at 4 institutions. Differences in postoperative overall survival (OS) and recurrence-free survival (RFS) according to EGFR mutation status were evaluated. For the genomic and transcriptomic analyses, 5 cohorts from public databases were evaluated.

Results: Of 466 eligible patients, 415 (89.1%) and 51 (10.9%) had CM and UCM, respectively. The 5-year OS and RFS rates in the CM/UCM groups were 86.8%/77.0% and 74.8%/59.0%, respectively. OS and RFS were significantly shorter in the UCM than CM group (both P < .01). Multivariable analysis of OS showed that UCM was an independent prognostic factor (hazard ratio 1.72, 95% confidential interval 1.01-2.93). According to the genomic analysis, tumors with UCM had a significantly higher tumor mutation burden and TP53 mutation frequency. Transcriptomic analysis showed that the T-cell-inflamed gene signature, a biomarker of the treatment for immunotherapy, was significantly associated with tumors with UCM.

Conclusion: UCM were associated with a poor prognosis in patients with surgically resected EGFR-mutated LUAD. Tumors with UCM had unique genomic and transcriptomic features suggestive of a tumor microenvironment responsive to immunotherapy.

Keywords: Genome; Lung adenocarcinoma; Surgery; Transcriptome; Uncommon EGFR mutation.

Publication types

Multicenter Study

MeSH terms

Adenocarcinoma of Lung* / genetics
Adenocarcinoma of Lung* / surgery
Adenocarcinoma* / pathology
ErbB Receptors / genetics
Gene Expression Profiling
Humans
Lung Neoplasms* / pathology
Mutation / genetics
Prognosis
Retrospective Studies
Tumor Microenvironment

Substances

ErbB Receptors
EGFR protein, human