Legumain: A biomarker for diagnosis and prognosis of human ovarian cancer

Legumain is a member of the asparaginyl endopeptidase family that is over-expressed in response to hypoxic stress on mammary adenocarcinoma, colorectal cancer, proliferating endothelial cells, and tumor-associated macrophages (TAMs). Here, we demonstrate that elevated expression of legumain in ovarian cancer by a proteomic approach using isobaric tags for relative and absolute quantification (iTRAQ) followed by liquid chromatographymass spectrometry (LCMS/MS). To investigate the relationship between legumain expression and ovarian cancer development, we tested legumain expression in malignant human ovarian tumors (n?=?60), borderline ovarian tumors (n?=?20), benign ovarian tumors (n?=?20), and normal ovary samples (n?=?20) using immunohistochemical assay (IHC). A correlation between legumain expression, and clinocopathologic and biological variables was also established. Importantly, increased legumain expression was validated by real-time PCR and Western blots, correlated positively with an increased malignancy of ovarian tumors (P?<?0.01). In fact, patients with strong legumain expression had a worse prognosis (P?=?0.03). In addition, results of in vitro experiments revealed that over-expression of legumain correlates with increased cell migration and invasion of ovarian cancer cells. Although legumain's functional role and clinical utility remain to be established, our results indicated that a sensitive assay for early expression of legumain may serve as both a potential biomarker and a molecular target for treatment of ovarian cancer. J. Cell. Biochem. 113: 26792686, 2012. (c) 2012 Wiley Periodicals, Inc.