Plasma Insulin-Like Growth Factor-Binding Protein-2 Levels as Diagnostic and Prognostic Biomarker of Colorectal Cancer

Context: Overexpression of IGF-II and IGF-binding protein (IGFBP)-2 has been reported in several cancers. Objective: We aimed to assess the roles of plasma IGF-II and IGFBP-2 levels as diagnostic and prognostic biomarkers and the impact of loss of imprinting (LOI) of IGF-II on the survival of colorectal cancer (CRC). Design: We conducted a case control and prospective cohort study for diagnostic and prognostic values, respectively. Patients and Setting: Plasma levels of IGF-II and IGFBP-2 were measured in 162 patients with CRC before surgery, in paired 15 patients after curative surgery, in 24 patients with advanced colon polyps, and in 114 healthy controls between 2003 and 2006 in National Taiwan University Hospital. Results: The area under the curve values of using IGFBP-2 as a diagnostic marker for advanced colon polyp and CRC were 0.654 [95% confidence interval (CI) = 0.547-0.76; P = 0.017] and 0.815 (95% CI = 0.766-0.864; P < 0.001), respectively. The sensitivity and specificity for diagnosing CRC were 80.2 and 64%, respectively, if the cutoff value of IGFBP-2 was 377 ng/ml. In the multivariate Cox proportional hazards regression model, higher IGFBP-2 levels were associated with increased risk of mortality [hazard ratio (HR) = 2.46; P = 0.017], whereas higher IGF-II levels were associated with reduced risk of mortality (HR = 0.42; P = 0.044). LOI of IGF-II was associated with increased risk of mortality (HR = 7.91; P = 0.014) in patients with stage IV disease. Conclusions: IGFBP-2 is a potential diagnostic and prognostic biomarker of CRC. LOI of IGF-II is significantly associated with poor prognosis in patients with stage IV disease. (J Clin Endocrinol Metab 95: 1717-1725, 2010)