Serum 27-nor-5β-Cholestane-3,7,12,24,25 Pentol Glucuronide Discovered by Metabolomics as Potential Diagnostic Biomarker for Epithelium Ovarian Cancer

被引:93
作者
Chen, Jing [2 ]
Zhang, Xiaoyan [1 ]
Cao, Rui [3 ]
Lu, Xin [2 ]
Zhao, Sumin [2 ]
Fekete, Agnes [4 ]
Huang, Qiang [2 ]
Schmitt-Kopplin, Philippe [4 ]
Wang, Yisheng [1 ]
Xu, Zhiliang [2 ]
Wan, Xiaoping [5 ]
Wu, Xiaohua [6 ]
Zhao, Naiqing [7 ]
Xu, Congjian [1 ]
Xu, Guowang [2 ]
机构
[1] Fudan Univ, Obstet & Gynecol Hosp, Shanghai Med Sch, Inst Biomed Sci,Shanghai Key Lab Female Reprod En, Shanghai 200011, Peoples R China
[2] Chinese Acad Sci, Dalian Inst Chem Phys, CAS Key Lab Separat Sci Analyt Chem, Dalian 116023, Peoples R China
[3] Dalian Med Univ, Dept Obstet & Gynecol Hosp, Dalian 116033, Peoples R China
[4] Helmholtz Zentrum Muenchen, German Res Ctr Environm Hlth, Dept BioGeoChem & Analyt, Inst Ecol Chem, D-85764 Neuherberg, Germany
[5] Shanghai Jiao Tong Univ, Sch Med, Int Peace Matern & Child Hlth Hosp, Shanghai 200030, Peoples R China
[6] Fudan Univ, Dept Gynecol Oncol, Canc Hosp, Shanghai 200032, Peoples R China
[7] Fudan Univ, Dept Biostat & Social Med, Sch Publ Hlth, Shanghai 200032, Peoples R China
基金
中国国家自然科学基金;
关键词
metabolomics; LC-MS; biomarker discovery; epithelium ovarian cancer; 27-nor-5 beta-cholestane-3,7,12,24,25 pentol glucuronide; CHROMATOGRAPHY-MASS-SPECTROMETRY; BILE ALCOHOL; SPECTROSCOPIC DATA; HEPATITIS-B; METABONOMICS; IDENTIFICATION; METABOLITE; FUTURE; URINE; EXPRESSION;
D O I
10.1021/pr200173q
中图分类号
Q5 [生物化学];
学科分类号
070307 [化学生物学];
摘要
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-5 beta-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 consumotion, 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.
引用
收藏
页码:2625 / 2632
页数:8
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