Systematic Survey of the Role of IGF in the Link Between Diabetes and Cancer

Abstract

Epidemiological studies have proposed a link between type II diabetes and cancer via the IGF/insulin signaling pathway, which includes insulin-like peptides (IGF1, IGF2, and insulin), insulin receptors (IR-A, IR-B, IGF1R, and hybrids), and insulin substrate proteins (IRS1–6). In this study, up- and down-regulation of various components in the IGF/insulin signaling pathway are compared to clinical outcomes for cancer patients; the components include diagnosis age, overall survival, tumor invasion and vascularization, and body mass index. It was found that the up-regulation of insulin growth Factor (IGF)/insulin components was associated with overall survival and tumor invasion and vascularization, while the down-regulation of equivalent components was not associated with clinical outcomes assessed in this study. Particularly, the up-regulation of DOK5, IGF2, and IRS2 in colorectal cancer and IGF1R in liver cancer is associated with significantly decreased overall survival. Functional aberrations in either of the two proteins in co-expression pairs were identified for each cancer and correlated with overall survival and diagnosis age. Specific biomarkers proposed in this study will be further analyzed to fine-tune consistent associations that can be translated to reliable prognostic standards for the roles of IGF/insulin signaling pathway modulations that promote cancer.

Insulin-Like Growth Factor 2 (IGF2) Signaling in Colorectal Cancer—From Basic Research to Potential Clinical Applications

“…Among others, it was proven that consumption of ≥15 g alcohol/day was associated with exclusively elevated risk of CRC with IGF2 DMR0 hypomethylation but not risk of cancer with high-level IGF2 DMR0 methylation, suggesting a possible mechanistic link between alcohol intake and CRC risk through IGF2 DMR0 hypomethylation during colorectal carcinogenesis [71]. The connections between IGF2 and type II diabetes mellitus (T2DM) and non-islet cell tumor hypoglycemia (NICTH) in etiology of this cancer are also examined [52,72,73]. Common IGF2 expression by tumor cells as well as autocrine action of this growth factor were also brought to attention, occasionally even reaching target tissues and causing tumor-induced hypoglycemia [74].…”

“…Common IGF2 expression by tumor cells as well as autocrine action of this growth factor were also brought to attention, occasionally even reaching target tissues and causing tumor-induced hypoglycemia [74]. While some studies did not show quantitative differences in IGF2 expression in CRC patients with T2DM, compared to those not affected by diabetes [75], newer research report that upregulation of DOK5, IGF2, and IRS2 in colorectal cancer and T2DM patients is associated with significantly decreased overall survival (OS) [73]. A role of IGF2 is implicated in preadipocyte differentiation and metabolism.…”

DOK5 as a Prognostic Biomarker of Gastric Cancer Immunoinvasion: A Bioinformatics Analysis

“…At present, surgery can be said to be the most efficient treatment for early GC, and 90% of patients will have a good prognosis [ 14 ]. However, resulting from the lack of early diagnosis, many patients are diagnosed at advanced stages, for example, about 65% of patients with stage 3 and stage 4 tumors, and nearly 85% of patients have lymph node metastasis [ 15 ]. In addition, treatment resistance often appears during the treatment of advanced GC.…”