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

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.

[1]  C. Lovly,et al.  Molecular Pathways: Clinical Applications and Future Direction of Insulin-like Growth Factor-1 Receptor Pathway Blockade , 2015, Clinical Cancer Research.

[2]  Yan-Ze Jin,et al.  Membranous Insulin-like Growth Factor-1 Receptor (IGF1R) Expression Is Predictive of Poor Prognosis in Patients with Epidermal Growth Factor Receptor (EGFR)-Mutant Lung Adenocarcinoma , 2015, Journal of pathology and translational medicine.

[3]  L. Girnita,et al.  Targeting the IGF-1R: The Tale of the Tortoise and the Hare , 2015, Front. Endocrinol..

[4]  Y. Suh,et al.  Regulation of IGF -1 signaling by microRNAs , 2014, Front. Genet..

[5]  W. Travis.  The 2015 WHO classification of lung tumors , 2014, Der Pathologe.

[6]  P. Haluska,et al.  Can we unlock the potential of IGF-1R inhibition in cancer therapy? , 2014, Cancer treatment reviews.

[7]  S. Stanilova,et al.  Association of insulin-like growth factor-I receptor polymorphism with colorectal cancer development , 2014, Molecular Biology Reports.

[8]  P. Petronini,et al.  Targeting PI3K/AKT/mTOR pathway in non small cell lung cancer. , 2014, Biochemical pharmacology.

[9]  Michael Thomas,et al.  Insulin-like growth factor 1 pathway mutations and protein expression in resected non-small cell lung cancer. , 2014, Human pathology.

[10]  A. Borczuk,et al.  Epidermal growth factor receptor mutations in lung adenocarcinoma , 2014, Laboratory Investigation.

[11]  C. Long-Smith,et al.  Insulin and IGF-1 signalling: longevity, protein homoeostasis and Alzheimer's disease. , 2012, Biochemical Society transactions.

[12]  G. Scagliotti,et al.  The role of the insulin-like growth factor signaling pathway in non-small cell lung cancer and other solid tumors. , 2012, Cancer treatment reviews.

[13]  M. Schubert,et al.  Central insulin and insulin-like growth factor-1 signaling: implications for diabetes associated dementia. , 2011, Current diabetes reviews.

[14]  K. Lim,et al.  Comparison of clinical outcome of patients with non-small-cell lung cancer harbouring epidermal growth factor receptor exon 19 or exon 21 mutations , 2011, Journal of Clinical Pathology.

[15]  J. Zha,et al.  Targeting the Insulin-like Growth Factor Receptor-1R Pathway for Cancer Therapy , 2010, Clinical Cancer Research.

[16]  Mu-Kuan Chen,et al.  Relationship of Insulin-Like Growth Factors System Gene Polymorphisms with the Susceptibility and Pathological Development of Hepatocellular Carcinoma , 2010, Annals of Surgical Oncology.

[17]  Balazs Halmos,et al.  Structure and clinical relevance of the epidermal growth factor receptor in human cancer. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[18]  Matthew Meyerson,et al.  Structures of lung cancer-derived EGFR mutants and inhibitor complexes: mechanism of activation and insights into differential inhibitor sensitivity. , 2007, Cancer cell.

[19]  Daniel A. Haber,et al.  Epidermal growth factor receptor mutations in lung cancer , 2007, Nature Reviews Cancer.

[20]  J. Minna,et al.  Clinical and biological features associated with epidermal growth factor receptor gene mutations in lung cancers. , 2006, Journal of the National Cancer Institute.

[21]  S. A,et al.  EGFR Mutations and Lung Cancer , 2005, PLoS Medicine.

[22]  S. Toyooka,et al.  PD-160 The relationship between epidermal growth factor receptor (EGFR) mutations and clinicopathologic features in non-small cell lung cancers , 2005 .

[23]  S. Toyooka,et al.  The relationship between epidermal growth factor receptor mutations and clinicopathologic features in non-small cell lung cancers. , 2005, Clinical cancer research : an official journal of the American Association for Cancer Research.

[24]  R. Wilson,et al.  EGF receptor gene mutations are common in lung cancers from "never smokers" and are associated with sensitivity of tumors to gefitinib and erlotinib. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[25]  S. Gabriel,et al.  EGFR Mutations in Lung Cancer: Correlation with Clinical Response to Gefitinib Therapy , 2004, Science.

[26]  Daniel Jones.  Anticancer drugs: To the rescue? , 2004, Nature Reviews Drug Discovery.

[27]  C. Franceschi,et al.  Polymorphic variants of insulin-like growth factor I (IGF-I) receptor and phosphoinositide 3-kinase genes affect IGF-I plasma levels and human longevity: cues for an evolutionarily conserved mechanism of life span control. , 2003, The Journal of clinical endocrinology and metabolism.