IGF-1 to IGFBP-2 ratio ≤0.85 a strong indicator of pancreatic adenocarcinoma

Insulin-like growth factor 1 (IGF-1) to insulin-like growth factor–binding protein 2 (IGFBP-2) ratio ≤0.85 appears to be a useful biomarker in the diagnosis of pancreatic adenocarcinoma (PDAC), suggests a recent study.

“This new direction of research is promising and may possibly improve PDAC detection,” the researchers said. “The presented data may also contribute to the explanation of the pathogenesis of diabetes in the course of pancreatic cancer.”

Sixty-nine patients with PDAC and 20 healthy controls were included in this study, which sought to assess the serum concentration levels of IGF-1 and IGFBP-2 to verify their potential role in the diagnosis of the disease. ELISA was used to estimate these concentrations. The Bioethics Committee at the Medical University of Lodz in Poland approved the study protocol.

Mean serum IGF-1 level was significantly lower in PDAC patients compared with controls (45.83±30.03 vs 70.66±60.57 ng/mL; p<0.0001). On the other hand, mean IGFBP-2 level was significantly higher in PDAC patients than in controls (225.06±86.37 vs 51.92±29.40 ng/mL; p<0.0001). [J Clin Gastroenterol 2020;54:e83-e88]

At the 0.01 sensitivity level, the IGF-1/IGFBP-2 ratio <0.85 points signaled the presence of PDAC. Moreover, this test demonstrated a specificity of 0.097 (α=0.01; β=0.097; IGF-1/IGFBP-2 ≤0.85) at this level of sensitivity.

Data published by Karna and colleagues contrasted these findings, showing higher serum IGF-1 in the control group than in PDAC patients (261±30 vs 162±28 ng/mL; p<0.01). The authors further suggested that deregulation of IGF-1 homeostasis may result in disturbances in tissue collagen metabolism during pancreatic diseases. [Int J Exp Pathol 2002;83:239-246]

Another study suggested that maintenance of a normal plasma IGF-1 concentration was needed for standard insulin sensitivity. Furthermore, states in which insulin was significantly increased (eg, hyperinsulinaemia in diabetes) correlated with lower serum IGF-1 concentrations. [Diabetes 2003;52:2483-2489; Horm Res 2004;62:77-82]

In some studies, elevated IGF-1 concentrations were associated with an increased risk of breast, prostate, and colon cancers, but the relationship between these proteins and PDAC risk was unclear. [J Natl Cancer Inst 1999;91:620-625; Lancet 1998;351:1393-1396; Eur J Cancer 1993;29A:492-497; Cancer Epidemiol Biomarkers Prev 2010;19:2877-2887]

In addition, researchers of the current study have shown that, “in our PDAC patients, the mean IGFBP-2 serum level was significantly higher compared with the control group. In the literature, [however], there is a relatively small number of publications concerning IGFBP-2, especially in PDAC.”

One study by Chen and colleagues reported elevated levels of IGFBP-2 in the pancreatic juice from a pancreatic cancer patient. They confirmed in the next study that marked overexpression of IGFBP-2 was detected in most of the cancer tissues. [Proteomics 2006;6:3871-3879; Mol Cell Proteomics 2007;6:1331-1342]

“IGF-1 and IGFBP-2 are proteins that belong to the IGF axis, which is involved in glucose and lipid metabolism and may as well promote carcinogenesis,” the researchers said. “Further studies in this area in a larger patient group are necessary to confirm our preliminary findings.”