Expression Characteristics of Proteins of the Insulin-like Growth Factor Axis in Non-small Cell Lung Cancer Patients with Preexisting Type 2 Diabetes Mellitus

Background: Preexisting type 2 diabetes mellitus (T2DM) affects the prognosis and mortality of patients withsome cancers. Insulin like growth factor (IGF) and insulin receptor (IR) signaling axes play important roles in bothcancer and diabetes development. We aimed to explore the expression characteristics of proteins in IGF/IR axisin non-small cell lung cancer (NSCLC) cases with preexisting T2DM.
Methods: Fifty-five NSCLC patients withpreexisting T2DM were retrospectively included and matched by 55 NSCLC without diabetes at a 1:1 ratio. Theexpression of proteins in IGF/IR axis was detected by immunohistochemical staining. Clinicopathological datawere collected to analyze their relationship with the protein expression.
Results: Both IGF 1 receptor (IGF-1R)and insulin receptor substrate 2 (IRS-2) showed higher expression in the NSCLC with T2DM group, comparedwith those without T2DM. The high expression of IGF-1R and IRS-2 were found to be negatively associated withlymph node metastases and T staging in the T2DM group, respectively, and IRS-2 expression was also found morein the subgroup whose T2DM duration was more than 4 years. No difference was detected in the expression ofIRS-1, IGF-1, IGF-2, IGFBP3, IR and mTOR between groups with or without T2DM.
Conclusion: Our studyfound higher expression of IGF-1R and IRS-2 proteins in NSCLC patients with preexisting T2DM, and thatthere was an association with early stage NSCLC, which suggested that IGF signaling may play an importantearly event in development of NSCLC associated with diabetes.