title: Serum 27-nor-5β-cholestane-3,7,12,24,25 pentol glucuronide discovered by metabolomics as potential diagnostic biomarker for epithelium ovarian cancer.
abstract: The aim of this study was to use a two steps strategy metabolomics to screen/identify and validate novel metabolic biomarker(s) for epithelial ovarian cancer (EOC). In the screening step, serum samples from 27 healthy women, 28 benign ovarian tumors, and 29 EOCs were analyzed by using LC-MS based nontargeted metabolomics. The three groups were separated with OSC filtered PLS-DA model, and six metabolites (27-nor-5β-cholestane-3,7,12,24,25 pentol glucuronide (CPG), phenylalanine, glycocholic acid, propionylcarnitine, Phe-Phe and Lyso PC (18:2)) were considered as potential biomarker candidates. In the validation step, the six metabolites were analyzed in targeted metabolomics by LC-selective ion monitoring mass spectrometry in another 685 serum samples with various clinical backgrounds. As a result, CPG was evaluated to be a potential biomarker and its content was elevated in EOC tissues compared with benign ovarian tumor tissues (p = 0.0005). Besides, CPG levels were found to be up-regulated in early stage EOC and in the three types of EOC histological types. Other variables such as nonovarian diseases, medicine consumption, gynecological inflammations, and menopausal state did not interfere in using CPG as diagnosis marker. CPG was found to be complementary to CA125. Our findings suggest that CPG can be considered a statistical relevant biomarker of EOC, ready for early stage detection.
authors: CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 116023 Dalian, China.
authors: Jing
authors: J
authors: Chen
authors: Xiaoyan
authors: X
authors: Zhang
authors: Rui
authors: R
authors: Cao
authors: Xin
authors: X
authors: Lu
authors: Sumin
authors: S
authors: Zhao
authors: Agnes
authors: A
authors: Fekete
authors: Qiang
authors: Q
authors: Huang
authors: Philippe
authors: P
authors: Schmitt-Kopplin
authors: Yisheng
authors: Y
authors: Wang
authors: Zhiliang
authors: Z
authors: Xu
authors: Xiaoping
authors: X
authors: Wan
authors: Xiaohua
authors: X
authors: Wu
authors: Naiqing
authors: N
authors: Zhao
authors: Congjian
authors: C
authors: Xu
authors: Guowang
authors: G
authors: Xu
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood*; D018394:CA-125 Antigen / Q000378:metabolism; D000077216:Carcinoma, Ovarian Epithelial; D002777:Cholestanols / Q000097:blood*; D002853:Chromatography, Liquid; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D020719:Glucuronides / Q000097:blood*; D006801:Humans; D013058:Mass Spectrometry; D008565:Membrane Proteins / Q000378:metabolism; D055432:Metabolomics / Q000379:methods*; D009375:Neoplasms, Glandular and Epithelial / Q000097:blood / Q000175:diagnosis; D010051:Ovarian Neoplasms / Q000097:blood / Q000175:diagnosis; D012372:ROC Curve
chemical_list: D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; D002777:Cholestanols; D020719:Glucuronides; C451759:MUC16 protein, human; D008565:Membrane Proteins; C030249:27-norcholestane-3,7,12,24,25-pentol