Biology of Human Tumors Elevated Serum Angiopoietin-like Protein 2 Correlates with the Metastatic Properties of Colorectal Cancer: A Serum Biomarker for Early Diagnosis and Recurrence

Purpose: Angiopoietin-like protein 2 (ANGPTL2) is a mediator of chronic inflammation and inflammatory carcinogenesis. The biologic and clinical significance of ANGPTL2 remains unknown in human cancer. Therefore, we investigated the function of ANGPTL2 and evaluated its clinical significance in both primary tumors and matched sera in patients with colorectal cancer. Experimental Design: A colorectal cancer cell line was transfected with siRNA against ANGPTL2 for the assessment of its function. We examined ANGPTL2 expression in colorectal cancer tissues (n 1⁄4 195) by immunohistochemistry. Finally, we screened serum ANGPTL2 levels from 32 colorectal cancers and 23 normal controls (NC), and validated these results in serum samples obtained from 195 colorectal cancers and 45 NCs by ELISA. Results: Knockdown of ANGPTL2 in vitro significantly inhibited cell proliferation, migration, and invasion, whereas it enhanced anoikis. ANGPTL2 was overexpressed in colorectal cancer tissues, and was significantly associated with advanced T stage, lymph node, and livermetastasis. Likewise, serumANGPTL2 levels in colorectal cancers were significantly higher than NCs (P < 0.01), and allowed distinguishing of colorectal cancers fromNCs with high accuracy (AUC1⁄4 0.837). The subsequent validation step confirmed that serumANGPTL2 levels in colorectal cancerswere significantly higher than inNCs (P< 0.0001), andhad a high AUC value (0.885) for distinguishing colorectal cancers from NCs. High serum ANGPTL2 was significantly associated with advanced T stage, lymph node and liver metastasis, early relapse, and poor prognosis in colorectal cancers. Conclusion: SerumANGPTL2 is a novel diagnostic and recurrence-predictive biomarker in patients with colorectal cancer. Clin Cancer Res; 20(23); 1–12. 2014 AACR.