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20 November 2019 : Clinical Research  

Epidermal Growth Factor Receptor Mutations in Resectable Non-Small Cell Lung Cancer Patients and their Potential Role in the Immune Landscape

Wei Xia1CDE, Wenjun Mao2ADEG*, Ruo Chen2BDF, Rongguo Lu2BD, Feng Liu2DF, Yijun He2DF, Shengfei Wang2F, Xiaomin Li3ADEG, Mingfeng Zheng2ADEG

DOI: 10.12659/MSM.920042

Med Sci Monit 2019; 25:8764-8776

Abstract

BACKGROUND: The epidermal growth factor receptor (EGFR) is a therapeutic target for non-small cell lung cancer (NSCLC), but knowledge on gene mutations that contribute to NSCLC development and persistence is lacking. In this study, we investigated genetic variations in EGFR and their association with the clinical and pathological factors of NSCLC.

MATERIAL AND METHODS: Clinical cases (331 patients) and The Cancer Genome Atlas (TCGA) cases (1040 patients) were selected and analyzed using the refractory mutation systems cBioPortal and the Tumor Immune Estimation Resource (TIMER).

RESULTS: EGFR mutation frequencies were 54.4% (180 of 331 patients) and 8.0% (83 of 1040 patients) in the clinical and TCGA cohorts, respectively. EGFR mutations were strongly associated with smoking and pathology (P≤0.05) in the clinical cohort, and with gender, smoking, and pathology (P=0.001, P<0.001, and P<0.001, respectively) in TCGA cohort. In cases of lung squamous carcinoma (LUSC), EGFR was overexpressed as a result of DNA amplification, but this amplified expression showed no association with the overall survival (OS) or progression-free survival of LUSC patients. EGFR gene alterations were, however, associated with worse OS in lung adenocarcinoma (LUAD) patients. Immune cell infiltrates from LUAD and LUSC tumors differed according to EGFR expression. EGFR mutations resulted in a decline of immune infiltration or a lack of infiltrating immune cells in the NSCLC microenvironment.

CONCLUSIONS: Mutational profiles of the EGFR in NSCLC patients provide useful information for the use of tyrosine kinase inhibitors for adjuvant or neoadjuvant therapy and immunotherapy.

Keywords: Mutation, Protein-Tyrosine Kinases, Receptor, Epidermal Growth Factor, Adenocarcinoma of Lung, Aged, 80 and over, Carcinoma, Squamous Cell, Cohort Studies, ErbB receptors, Lung, Protein Kinase Inhibitors, tumor microenvironment

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750