Clinical significance of serum angiopoietin-like protein 2 in colorectal cancer patients.

417 Background: Angiopoietin-like protein 2 (ANGPTL2) is a secreted protein belonging to the angiopoietin family. It has been reported to act as a causative mediator of chronic inflammation and metabolic abnormalities. ANGPTL2 increases inflammatory carcinogenesis in several cancers, and its expression in tumor cells is highly correlated with the frequency of tumor cell metastasis through increased tumor angiogenesis and tumor cell epithelial-to-mesenchymal transitions. However, to our own knowledge, clinical significance of serum ANGPTL2 in cancer patients remains unknown. The aim of this study was to quantify serum ANGPTL2 level using ELISA, and to evaluate its clinical and prognostic significance in patients with colorectal cancer (CRC). Methods: We quantified serum ANGPTL2 levels from 194 CRC patients and normal 48 controls (NC) by ELISA. Next, we investigated ANGPTL2 expression in matched CRC tissues (n=194) by immunohistochemistry (IHC) to identify the source of circulating ANGPTL2. The IHC score of ANGPTL2 was determined on the basis of both staining intensity and the percentage of positive cells. Results: Serum ANGPTL2 levels were significantly higher in CRC than in NC (p<0.01) and gradually increased according to TNM stage progression. Serum ANGPTL2 levels discriminated CRC from NC with high accuracy (AUC=0.837). High serum ANGPTL2 was significantly associated with larger tumor size (p=0.03), undifferentiated adenocarcinoma (p=0.03), advanced T stage (p<0.01), peritoneal metastasis (p<0.01). In addition, Kaplan–Meier curves revealed that high serum ANGPTL2 were significantly associated with poor disease free survival (p=0.01) and overall survival (p=0.03). Interestingly, ANGPTL2 levels in serum from CRC patients closely correlated with IHC scores of cytoplasmic ANGPTL2 expression in matched CRC tissues (r=0.14, p=0.03). Conclusions: Serum ANGPTL2, which might be derived from primary CRC tumor, has strong potential to serve as a noninvasive biomarker for CRC diagnosis and prognosis.