title: High resolution mass spectrometry coupled with multivariate data analysis revealing plasma lipidomic alteration in ovarian cancer in Asian women.
abstract: Ovarian cancer (OC) is the most common cause of death from gynecologic malignancies in women. The identification of reliable diagnostic biomarkers for the early detection of this deadly disease is critical for reducing the mortality rate of OC. Plasma lysophosphatidic acid (LPA) levels were increased from OC patients vs. healthy controls. Therefore, lipidomics may represent an excellent developing prospect for the discovery of diagnostic biomarkers of OC. In this study, a nontargeted lipidomics approach based on ultra performance liquid chromatography-electrospray ionization-QTOF-mass spectrometry (UPLC-ESI-QTOF-MS) combined with multivariate data analysis, including principal component analysis (PCA) and (orthogonal) partial least squared discriminant analysis [(O)PLS-DA] was applied for the investigation of potential diagnostic biomarkers in plasma of OC patients. Patients with OC could be distinguished from healthy individuals and patients with benign gynecological tumor disease by this method, which shows a significant lipid perturbation in this disease. With the assistance of high resolution and high accuracy of MS and MS/MS data, the potential markers including lysophosphatidylcholines (LPCs), phosphatidylcholines (PCs) and triacylglycerols (TGs) with specific fatty acid chains, were identified. Interestingly, LPCs were up-regulated and PCs and TGs were down-regulated, compared OC group with benign tumor and normal control groups, and the glycerophospholipid metabolism emerged as a key pathway, in particular, the phospholipase A2 (PLA2) enzyme activity, that was disregulated in the disease. This study may provide new insight into underlying mechanisms for OC and proves that MS-based lipidomics is a powerful method in discovering new potential clinical biomarkers for diseases.
authors.affiliation: Beijing National Laboratory for Molecular Sciences, Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry Chinese Academy of Sciences, Beijing Mass Spectrum Center, Beijing 100190, China.
authors.forename: Yangyang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Obstetrics and Gynecology, Peking University Shougang Hospital, Beijing 100144, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Beijing National Laboratory for Molecular Sciences, Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry Chinese Academy of Sciences, Beijing Mass Spectrum Center, Beijing 100190, China; Graduate School, University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.affiliation: Beijing National Laboratory for Molecular Sciences, Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry Chinese Academy of Sciences, Beijing Mass Spectrum Center, Beijing 100190, China.
authors.forename: Jinchao
authors.initials: J
authors.lastname: Wei
authors.affiliation: Beijing National Laboratory for Molecular Sciences, Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry Chinese Academy of Sciences, Beijing Mass Spectrum Center, Beijing 100190, China.
authors.forename: Shaoxiang
authors.initials: S
authors.lastname: Xiong
authors.affiliation: Beijing National Laboratory for Molecular Sciences, Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry Chinese Academy of Sciences, Beijing Mass Spectrum Center, Beijing 100190, China; Graduate School, University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address: zhenwenzhao@iccas.ac.cn.
authors.forename: Zhenwen
authors.initials: Z
authors.lastname: Zhao
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D044466:Asian People; D014408:Biomarkers, Tumor / Q000097:blood; D002648:Child; D002851:Chromatography, High Pressure Liquid; D016002:Discriminant Analysis; D005260:Female; D006801:Humans; D008055:Lipids / Q000097:blood*; D055432:Metabolomics / Q000379:methods*; D008875:Middle Aged; D015999:Multivariate Analysis; D010051:Ovarian Neoplasms / Q000097:blood* / Q000378:metabolism*; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D008055:Lipids
keywords: Glycerophospholipid metabolism; Lipidomics; Mass spectrometry; Multivariate data analysis; Ovarian cancer