title: Legumain: a biomarker for diagnosis and prognosis of human ovarian cancer.
abstract: 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 chromatography-mass spectrometry (LC-MS/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.
authors.affiliation: Department of Immunology, Nankai University School of Medicine, Tianjin, China.
authors.forename: Lina
authors.initials: L
authors.lastname: Wang
authors.forename: Si
authors.initials: S
authors.lastname: Chen
authors.forename: Mingna
authors.initials: M
authors.lastname: Zhang
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.forename: Yanan
authors.initials: Y
authors.lastname: Chen
authors.forename: Weijun
authors.initials: W
authors.lastname: Su
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Liu
authors.forename: Dan
authors.initials: D
authors.lastname: Lu
authors.forename: Sanglin
authors.initials: S
authors.lastname: Li
authors.forename: Yixuan
authors.initials: Y
authors.lastname: Yang
authors.forename: Zongjin
authors.initials: Z
authors.lastname: Li
authors.forename: Dwayne
authors.initials: D
authors.lastname: Stupack
authors.forename: Pengpeng
authors.initials: P
authors.lastname: Qu
authors.forename: Huaidong
authors.initials: H
authors.lastname: Hu
authors.forename: Rong
authors.initials: R
authors.lastname: Xiang
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D002465:Cell Movement / Q000235:genetics / Q000502:physiology; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D010051:Ovarian Neoplasms / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D000099240:Asparaginyl Endopeptidase
chemical_list: D014408:Biomarkers, Tumor; D003546:Cysteine Endopeptidases; D000099240:Asparaginyl Endopeptidase