The Clinical Significance of the Insulin-Like Growth Factor-1 Receptor Polymorphism in Non-Small-Cell Lung Cancer with Epidermal Growth Factor Receptor Mutation.

Tu-Chen Liu,Whei-Ling Chiang,Shun-Fa Yang,Thomas Tsao,Ming-Che Liu,Ming-Ju Hsieh

doi:10.3390/ijms17050763

Abstract

The insulin-like growth factor 1 (IGF1) signaling pathway mediates multiple cancer cell biological processes. IGF1 receptor (IGF1R) expression has been used as a reporter of the clinical significance of non-small-cell lung carcinoma (NSCLC). However, the association between IGF1R genetic variants and the clinical utility of NSCLC positive for epidermal growth factor receptor (EGFR) mutation is not clear. The current study investigated the association between the IGF1R genetic variants, the occurrence of EGFR mutations, and clinicopathological characteristics in NSCLC patients. A total of 452 participants, including 362 adenocarcinoma lung cancer and 90 squamous cell carcinoma lung cancer patients, were selected for analysis of IGF1R genetic variants (rs7166348, rs2229765, and rs8038415) using real-time polymerase chain reaction (PCR)genotyping. The results indicated that GA + AA genotypes of IGF1R rs2229765 were significantly associated with EGFR mutation in female lung adenocarcinoma patients (odds ratio (OR) = 0.39, 95% confidence interval (CI) = 0.17–0.87). Moreover, The GA + AA genotype IGF1R rs2229765 was significantly associated with EGFR L858R mutation (p = 0.02) but not with the exon 19 in-frame deletion. Furthermore, among patients without EGFR mutation, those who have at least one polymorphic A allele of IGF1R rs7166348 have an increased incidence of lymph node metastasis when compared with those patients homozygous for GG (OR, 2.75; 95% CI, 1.20–2.31). Our results showed that IGF1R genetic variants are related to EGFR mutation in female lung adenocarcinoma patients and may be a predictive factor for tumor lymph node metastasis in Taiwanese patients with NSCLC.

Highlights

Lung cancer is a common type of cancer worldwide [1]
The results showed that high membranous IGF1 receptor (IGF1R) expression was predictive of poor progression-free survival (PFS) in adenocarcinoma, but had better PFS in squamous cell carcinoma [19]
These results indicate that the polymorphisms of IGF1R rs2229765 gene are associated with L858R mutation in female adenocarcinoma patients

Summary

Introduction

Lung cancer is a common type of cancer worldwide [1]. Two primary types of lung cancer are small cell lung carcinoma (SCLC) and non-small-cell lung carcinoma (NSCLC). It has been reported that mutation in the TK domain of EGFR gene is associated with NSCLC [6,7,8]. The most common mutations in the TK domain of EGFR are the in-frame deletion mutation in exon 19 and the substitution mutation (L858R) in exon 21. Mutation in the TK domain of EGFR causes the conformational change in protein structure. This results in constitutive TK activity and its downstream signaling pathway [9,10]. It has been reported that gefitinib and erlotinib are EGFR tyrosine kinase inhibitors (TKIs) for in-frame deletion in exon 19 and the substitution mutation (L858R) in exon 21 [6,7,8]

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