title: Discovery of specific metastasis-related N-glycan alterations in epithelial ovarian cancer based on quantitative glycomics.
abstract: Generally, most of ovarian cancer cannot be detected until large scale and remote metastasis occurs, which is the major cause of high mortality in ovarian cancer. Therefore, it is urgent to discover metastasis-related biomarkers for the detection of ovarian cancer in its occult metastasis stage. Altered glycosylation is a universal feature of malignancy and certain types of glycan structures are well-known markers for tumor progressions. Thus, this study aimed to reveal specific changes of N-glycans in the secretome of the metastatic ovarian cancer. We employed a quantitative glycomics approach based on metabolic stable isotope labeling to compare the differential N-glycosylation of secretome between an ovarian cancer cell line SKOV3 and its high metastatic derivative SKOV3-ip. Intriguingly, among total 17 N-glycans identified, the N-glycans with bisecting GlcNAc were all significantly decreased in SKOV3-ip in comparison to SKOV3. This alteration in bisecting GlcNAc glycoforms as well as its corresponding association with ovarian cancer metastatic behavior was further validated at the glycotransferase level with multiple techniques including real-time PCR, western blotting, transwell assay, lectin blotting and immunohistochemistry analysis. This study illustrated metastasis-related N-glycan alterations in ovarian cancer secretome in vitro for the first time, which is a valuable source for biomarker discovery as well. Moreover, N-glycans with bisecting GlcNAc shed light on the detection of ovarian cancer in early peritoneal metastasis stage which may accordingly improve the prognosis of ovarian cancer patients.
authors: Key Laboratory of Glycoconjugate Research Ministry of Public Health, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
authors: Xingwang
authors: X
authors: Zhang
authors: Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China.
authors: Yisheng
authors: Y
authors: Wang
authors: Key Laboratory of Glycoconjugate Research Ministry of Public Health, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
authors: Yifan
authors: Y
authors: Qian
authors: Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China.
authors: Xin
authors: X
authors: Wu
authors: Key Laboratory of Glycoconjugate Research Ministry of Public Health, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
authors: Zejian
authors: Z
authors: Zhang
authors: Key Laboratory of Glycoconjugate Research Ministry of Public Health, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
authors: Xijun
authors: X
authors: Liu
authors: Institute of Biomedical Sciences, Fudan University, Shanghai, China.
authors: Ran
authors: R
authors: Zhao
authors: Key Laboratory of Glycoconjugate Research Ministry of Public Health, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
authors: Lei
authors: L
authors: Zhou
authors: Key Laboratory of Glycoconjugate Research Ministry of Public Health, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
authors: Yuanyuan
authors: Y
authors: Ruan
authors: Key Laboratory of Glycoconjugate Research Ministry of Public Health, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
authors: Jiejie
authors: J
authors: Xu
authors: Key Laboratory of Glycoconjugate Research Ministry of Public Health, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
authors: Haiou
authors: H
authors: Liu
authors: Key Laboratory of Glycoconjugate Research Ministry of Public Health, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
authors: Shifang
authors: S
authors: Ren
authors: Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China ; Department of Obstetrics and Gynecology of Shanghai Medical School, Fudan University, Shanghai, China ; Institute of Biomedical Sciences, Fudan University, Shanghai, China ; Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, China.
authors: Congjian
authors: C
authors: Xu
authors: Key Laboratory of Glycoconjugate Research Ministry of Public Health, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
authors: Jianxin
authors: J
authors: Gu
mesh_terms: D000077216:Carcinoma, Ovarian Epithelial; D045744:Cell Line, Tumor; D002465:Cell Movement; D005260:Female; D055785:Gene Knockdown Techniques; D054794:Glycomics / Q000379:methods*; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D017351:N-Acetylglucosaminyltransferases / Q000378:metabolism; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009375:Neoplasms, Glandular and Epithelial / Q000378:metabolism* / Q000473:pathology*; D009587:Nitrogen Isotopes; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology*; D011134:Polysaccharides / Q000378:metabolism*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D009587:Nitrogen Isotopes; D011134:Polysaccharides; D017351:N-Acetylglucosaminyltransferases; C054599:beta-1,4-mannosyl-glycoprotein beta-1,4-N-acetylglucosaminyltransferase