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

Abstract

Background: Preexisting type 2 diabetes mellitus (T2DM) affects the prognosis and mortality of patients with some cancers. Insulin like growth factor (IGF) and insulin receptor (IR) signaling axes play important roles in both cancer and diabetes development. We aimed to explore the expression characteristics of proteins in IGF/IR axis in non-small cell lung cancer (NSCLC) cases with preexisting T2DM. Methods: Fifty-five NSCLC patients with preexisting T2DM were retrospectively included and matched by 55 NSCLC without diabetes at a 1:1 ratio. The expression of proteins in IGF/IR axis was detected by immunohistochemical staining. Clinicopathological data were 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, compared with those without T2DM. The high expression of IGF-1R and IRS-2 were found to be negatively associated with lymph node metastases and T staging in the T2DM group, respectively, and IRS-2 expression was also found more in the subgroup whose T2DM duration was more than 4 years. No difference was detected in the expression of IRS-1, IGF-1, IGF-2, IGFBP3, IR and mTOR between groups with or without T2DM. Conclusion: Our study found higher expression of IGF-1R and IRS-2 proteins in NSCLC patients with preexisting T2DM, and that there was an association with early stage NSCLC, which suggested that IGF signaling may play an important early event in development of NSCLC associated with diabetes.

Lack of any Prognostic Role of Insulin-Like Growth Factor-1 Receptor in Non-Small Cell Lung Cancer

“…It was demonstrated that addition of anti-IGF1R treatment to paclitaxelcarboplatin combination therapy in NSCLC improved the response to treatment (Gualberto and Karp, 2009;Karp et al, 2009;Goto et al, 2012;Chen et al, 2013). Studies have shown that there could be a correlation between K-Ras status and IGF1R expression.…”

“…It has been demonstrated that IGF1R plays an important role in the development and progression of many cancers such as prostate, breast, liver, and colorectal cancers and brain tumors (Resnik et al,1998;O'Brien et al, 2001;Alexia et al, 2004;Samani et al, 2007;Xiong et al, 2012;Li et al, 2013). Even though studies performed to assess the role of IGF1R in lung cancer have given conflicting results, the common outcome of the studies is that IGF1R may be an autocrine growth factor for lung cancer (Ding et al, 2013;Vincent et al, 2013). The purpose of this study was to determine whether IGF1R expression evaluated by an immunohistochemical method would have a prognostic role in non-small cell lung cancer (NSCLC).…”

Role of Hyperinsulinemia in Increased Risk of Prostate Cancer: A Case Control Study from Kathmandu Valley

“…Hyperglycemia make available energy for malignant cell production and, via the peculiar energy utilization of cancer cells, favors cancer growth and neoangiogenesis (Ding et al, 2013). Also high serum glucose shows the way to swift augmentation of insulin from the pancreatic beta cells, and elevated insulin levels can be allied with insulin resistance.…”

Anti-Diabetic Medications Do Not Influence Risk of Lung Cancer in Patients with Diabetes Mellitus: a Systematic Review and Meta-analysis

“…Despite advances in early diagnosis and treatment modalities, prognosis remains poor; the five-year survival rate is only about 15% (Mulshine et al, 2005). Individuals at risk for developing lung cancer can be identified by clinical epidemiologic factors (Bach et al, 2003;Spitz et al, 2007;Cassidy et al, 2008;Tammemagi et al, 2011;Ding et al, 2013) and it has been well established that tobacco smoking is the most important cause of lung cancer, accounting for 85%-90% of all cases in the world (Ruano-Ravina et al, 2003;Tyczynski et al, 2003). The remaining cases were attributable to nonsmoking causes such as pulmonary tuberculosis, environmental exposure to radon and arsenic in drinking water in homes, occupational exposure to asbestos and other carcinogens, as well as family history of lung cancer (Lam et al, 2004; RESEARCH ARTICLE Bruske-Hohlfeld, 2009;Gao et al, 2009;WU et al, 2011).…”