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EGFR-mutated squamous cell lung cancer and its association with outcomes

Title: EGFR-mutated squamous cell lung cancer and its association with outcomes
Authors: Jin, R
Peng, L
Shou, J
Wang, J
Jin, Y
Liang, F
Zhao, J
Wu, M
Li, Q
Zhang, B
Wu, X
Lan, F
Xia, L
Yan, J
Shao, Y
Stebbing, J
Shen, H
Li, W
Xia, Y
Item Type: Journal Article
Abstract: Background: The therapeutic efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in advanced EGFR-mutant lung squamous cell carcinoma (SCC) patients remains uncertain. Furthermore, the factors underlying the responsiveness have not been fully investigated. We therefore investigated the link between genomic profiles and EGFR-TKI efficacy. Material and Methods: We consecutively enrolled stage IV, EGFR-mutant, and EGFR-TKI-treated patients with SCC. Patients with EGFR wild-type lung SCC and EGFR-mutant lung adenocarcinoma were consecutively enrolled as controls, and next-generation sequencing (NGS) was performed. Results: In total, 28 EGFR-mutant lung SCC, 41 EGFR-mutant lung adenocarcinoma, and 40 EGFR wild-type lung SCC patients were included. Among the patients with EGFR mutations, shorter progression-free survival (PFS) was observed in SCC compared to adenocarcinoma (4.6 vs. 11.0 months, P<0.001). Comparison of the genomic profiles revealed that EGFR-mutant SCC patients had similar mutation characteristics to EGFR-mutant adenocarcinoma patients, but differed from those with EGFR wild-type SCC. Further exploration of EGFR-mutant SCC revealed that mutations in CREBBP (P = 0.005), ZNF217 (P = 0.016), and the Wnt (P = 0.027) pathway were negatively associated with PFS. Mutations in GRM8 (P = 0.025) were associated with improved PFS. Conclusions: EGFR-mutant lung SCC has a worse prognosis than EGFR-mutant adenocarcinoma. Mutations in other genes, such as CREBBP, ZNF217, GRM8, or Wnt that had implications on PFS raise the possibility of understanding mechanisms of resistance to EGFR-TKI in lung SCC, which will aid identification of potential beneficial subgroups of patients with EGFR-mutant SCCs receiving EGFR-TKIs.
Issue Date: 14-Jun-2021
Date of Acceptance: 26-May-2021
URI: http://hdl.handle.net/10044/1/90152
DOI: 10.3389/fonc.2021.680804
ISSN: 2234-943X
Publisher: Frontiers Media
Journal / Book Title: Frontiers in Oncology
Volume: 11
Copyright Statement: © 2021 Jin, Peng, Shou, Wang, Jin, Liang, Zhao, Wu, Li, Zhang, Wu, Lan, Xia, Yan, Shao, Stebbing, Shen, Li and Xia. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Sponsor/Funder: National Institute for Health Research
Imperial College Healthcare NHS Trust- BRC Funding
Funder's Grant Number: NIHR-RP-011-053
RDB01 79560
Keywords: epidermal growth factor receptor
genomic profile
lung squamous cell carcinoma
progression-free survival
tyrosine kinase inhibitor
epidermal growth factor receptor
genomic profile
lung squamous cell carcinoma
progression-free survival
tyrosine kinase inhibitor
1112 Oncology and Carcinogenesis
Publication Status: Published
Conference Place: Switzerland
Article Number: ARTN 680804
Appears in Collections:Department of Surgery and Cancer



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