Lysophospholipids Are Potential Biomarkers of Ovarian Cancer

Author:

Sutphen Rebecca1,Xu Yan2,Wilbanks George D.3,Fiorica James13,Grendys Edward C.13,LaPolla James P.4,Arango Hector5,Hoffman Mitchell S.6,Martino Martin3,Wakeley Katie37,Griffin David6,Blanco Rafael W.8,Cantor Alan B.1,Xiao Yi-jin2,Krischer Jeffrey P.1

Affiliation:

1. 1Interdisciplinary Oncology, Departments of

2. 4Cleveland Clinic Foundation, Cleveland, Ohio;

3. 2Obstetrics and Gynecology, and

4. 5Department of Gynecologic Oncology, Bayfront Medical Center, St. Petersburg, Florida;

5. 6Morton Plant Hospital, Clearwater, Florida;

6. 3Gynecologic Oncology, College of Medicine and H. Lee Moffitt Cancer Center and Research Institute, University of South Florida, Tampa, Florida;

7. 7New England Medical Center, Tufts University, Boston, Massachusetts; and

8. 8Bay Area Oncology, Tampa, Florida

Abstract

Abstract Objective: To determine whether lysophosphatidic acid (LPA) and other lysophospholipids (LPL) are useful markers for diagnosis and/or prognosis of ovarian cancer in a controlled setting. Method: Plasma samples were collected from ovarian cancer patients and healthy control women in Hillsborough and Pinellas counties, Florida, and processed at the University of South Florida H. Lee Moffitt Cancer Center and Research Institute (Moffitt). Case patients with epithelial ovarian cancer (n = 117) and healthy control subjects (n = 27) participated in the study. Blinded LPL analysis, including 23 individual LPL species, was performed at the Cleveland Clinic Foundation using an electrospray ionization mass spectrometry–based method. LPL levels were transmitted to Moffitt, where clinical data were reviewed and statistical analyses were performed. Results: There were statistically significant differences between preoperative case samples (n = 45) and control samples (n = 27) in the mean levels of total LPA, total lysophosphatidylinositol (LPI), sphingosine-1-phosphate (S1P), and individual LPA species as well as the combination of several LPL species. The combination of 16:0-LPA and 20:4-LPA yielded the best discrimination between preoperative case samples and control samples, with 93.1% correct classification, 91.1% sensitivity, and 96.3% specificity. In 22 cases with both preoperative and postoperative samples, the postoperative levels of several LPL, including S1P, total LPA, and lysophosphatidylcholine (LPC) levels and some individual species of LPA and LPC, were significantly different from preoperative levels. Conclusion: LPA, LPI, LPC, and S1P appear useful as diagnostic and prognostic biomarkers of ovarian cancer.

Publisher

American Association for Cancer Research (AACR)

Subject

Oncology,Epidemiology

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