Lysophospholipids as Biomarkers: Ova Ca (LPA)

Lysophospholipids Are Potential Biomarkers of Ovarian Cancer

Rebecca Sutphen1, Yan Xu4, George D. Wilbanks2, James Fiorica1,2, Edward C. Grendys, Jr.1,2, James P. LaPolla5, Hector Arango6, Mitchell S. Hoffman3, Martin Martino2, Katie Wakeley2,7, David Griffin3, Rafael W. Blanco8, Alan B. Cantor1, Yi-jin Xiao4 and Jeffrey P. Krischer1 Departments of 1 Interdisciplinary Oncology, 2 Obstetrics and Gynecology, and 3 Gynecologic Oncology, College of Medicine and H. Lee Moffitt Cancer Center and Research Institute, University of South Florida, Tampa, Florida; 4 Cleveland Clinic Foundation, Cleveland, Ohio; 5 Department of Gynecologic Oncology, Bayfront Medical Center, St. Petersburg, Florida; 6 Morton Plant Hospital, Clearwater, Florida; 7 New England Medical Center, Tufts University, Boston, Massachusetts; and 8 Bay Area Oncology, Tampa, Florida

Requests for reprints: Rebecca Sutphen, H. Lee Moffitt Cancer Center and Research Institute, University of South Florida, 12902 Magnolia Drive, FOW-LCS, Tampa, FL 33612.

Phone: 813-903-4990; Fax: 813-558-4807. E-mail: rsutphen@hsc.usf.edu

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.

Cancer Epidemiology Biomarkers & Prevention Vol. 13, 1185-1191, July 2004

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