Prognostic implications of tumoral expression of insulin like growth factors 1 and 2 in patients with non-small-cell lung cancer

Clin Lung Cancer. 2014 May;15(3):213-21. doi: 10.1016/j.cllc.2013.12.006. Epub 2014 Jan 1.


Introduction: The currently available systemic therapies for non-small-cell lung cancer (NSCLC) have limited efficacy. Previous studies indicated an association of elevated insulinlike growth factor (IGF)-1 receptor (IGF-1R) and insulin receptor expression levels with poor survival in patients with NSCLC. To better understand the molecular biomarkers involved in the IGF signaling pathway in NSCLC, the expression levels of IGF-1 and IGF-2 are characterized and evaluated for their association with IGF-1R and phosphorylated IGF-1R (pIGF-1R) expression in NSCLC.

Materials and methods: A total of 352 patients who underwent NSCLC resection with curative intent were studied. The expression patterns of the IGF-1, IGF-2, IGF-1R, and pIGF-1R proteins were assessed immunohistochemically using tissue microarrays.

Results: The IGF-1 expression was higher in patients with adenocarcinoma (ADC) than in those with squamous cell carcinoma (SCC), whereas the IGF-2 score was higher in patients with SCC than those with ADC. Likewise, the IGF-1 score was higher in patients with mutated epidermal growth factor receptor (mtEGFR) than in those with wild type EGFR (wtEGFR), whereas the IGF-2 score was higher in patients with wtEGFR than in those with mtEGFR. Patients with low levels of IGF-1 expression had longer overall survival (OS) than those with high IGF-1 expression, and subgroup analyses found a significant difference in OS only in patients with ADC.

Conclusion: The overexpression of IGF-1 predicts poor survival among patients with NSCLC, especially those with ADC. These results might serve as a future guide for clinical trials involving IGF-1R-targeting agents.

Keywords: Carcinoma; IGF Type 1; IGF Type 2; Non–Small-Cell Lung; Prognosis; Survival.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / pathology
  • Adenocarcinoma / surgery
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Non-Small-Cell Lung / surgery
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Insulin-Like Growth Factor I / genetics*
  • Insulin-Like Growth Factor II / genetics*
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Lung Neoplasms / surgery
  • Male
  • Middle Aged
  • Prognosis
  • Receptor, IGF Type 1 / genetics
  • Survival Rate
  • Tissue Array Analysis


  • Biomarkers, Tumor
  • Insulin-Like Growth Factor I
  • Insulin-Like Growth Factor II
  • Receptor, IGF Type 1