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

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/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.

<p>Decreased PTGDS Expression Predicting Poor Survival of Endometrial Cancer by Integrating Weighted Gene Co-Expression Network Analysis and Immunohistochemical Validation</p>

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Using Weighted Gene Co-Expression Network Analysis to Identify Increased MND1 Expression as a Predictor of Poor Breast Cancer Survival

“…Anti-cancer medicines also target immune cell infiltration. 54 TIMER analysis showed the expression of MND1 is positively correlated with the infiltration level of B cells, CD8 + T cells, CD4 + T cells, macrophages, neutrophils, and dendritic cells in BC patients. Immune cell infiltration deficiency or malfunctioning in malignancies can lead to immune escape and increase tumor development.…”

Neoadjuvant immunotherapy for non–small cell lung cancer: State of the art

“…Approximately 20% of NSCLCs carrying EGFR mutations undergo hyper‐progression. EGFR mutations are associated with decreased immune infiltration or a lack of infiltrating immune cells in the NSCLC microenvironment [90], suggesting a higher incidence of progression for EGFR ‐mutated NSCLC. In addition, the incidence of AEs is significantly higher in NSCLC patients carrying EGFR mutations.…”