Lysophospholipids Are Potential Biomarkers of Ovarian Cancer

Cancer Epidemiology Biomarkers and Prevention - Tập 13 Số 7 - Trang 1185-1191 - 2004
Rebecca Sutphen1, Yan Xu2, George D. Wilbanks3, James V. Fiorica1,3, Edward C. Grendys1,3, James P. LaPolla4, Hector Arango5, Mitchell Hoffman6, Martin A Martino3, Katie Wakeley3,7, David Ray Griffin6, Rafael W. Blanco8, Alan Cantor1, Yijin Xiao2, Jeffrey P. Krischer1
11Interdisciplinary Oncology, Departments of
24Cleveland Clinic Foundation, Cleveland, Ohio;
32Obstetrics and Gynecology, and
45Department of Gynecologic Oncology, Bayfront Medical Center, St. Petersburg, Florida;
56Morton Plant Hospital, Clearwater, Florida;
63Gynecologic Oncology, College of Medicine and H. Lee Moffitt Cancer Center and Research Institute, University of South Florida, Tampa, Florida;
77New England Medical Center, Tufts University, Boston, Massachusetts; and
88Bay Area Oncology, Tampa, Florida

Tóm tắt

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.

Từ khóa


Tài liệu tham khảo

American Cancer Society. Cancer facts and figures 2003. American Cancer Society [accessed 2003 Apr]. Available from: http://www.cancer.org/docroots/STT/stt_0.asp.

Mok SC, Chao J, Skates S, et al. Prostasin, a potential serum marker for ovarian cancer: identification through microarray technology. J Natl Cancer Inst 2001;93:1458-64.

Schwartz PE, Taylor KJ. Is early detection of ovarian cancer possible? Ann Med 1995;27:519-28.

Taylor KJ, Schwartz PE. Screening for early ovarian cancer. Radiology 1994;192:1-10.

Greenlee RT, Hill-Harmon MB, Murray T, Thun M. Cancer statistics, 2001. CA Cancer J Clin 2001;51:15-36.

Bast RC Jr, Xu FJ, Yu YH, Barnhill S, Zhang Z, Mills GB. CA 125: the past and the future. Int J Biol Markers 1998;13:179-87.

Petricoin EF, Ardekani AM, Hitt BA, et al. Use of proteomic patterns in serum to identify ovarian cancer. Lancet 2002;359:572-7.

Xu Y, Shen Z, Wiper DW, et al. Lysophosphatidic acid as a potential biomarker for ovarian and other gynecologic cancers. JAMA 1998;280:719-23.

Kim H, Hye-Ran Y, Pyo D. Quantitative analysis of lysophosphatidic acid in human plasma by tandem mass spectrometry. Bull Korean Chem Soc 2002;23:1139-43.

Baker DL, Morrison P, Miller B, et al. Plasma lysophosphatidic acid concentration and ovarian cancer. JAMA 2002;287:3081-2.

Xu Y, Fang XJ, Casey G, Mills GB. Lysophospholipids activate ovarian and breast cancer cells. Biochem J 1995;309 Pt 3:933-40.

Xu Y, Gaudette DC, Boynton JD, et al. Characterization of an ovarian cancer activating factor in ascites from ovarian cancer patients. Clin Cancer Res 1995;1:1223-32.

Gaits F, Salles JP, Chap H. Dual effect of lysophosphatidic acid on proliferation of glomerular mesangial cells. Kidney Int 1997;51:1022-7.

Gennero I, Xuereb JM, Simon MF, et al. Effects of lysophosphatidic acid on proliferation and cytosolic Ca++ of human adult vascular smooth muscle cells in culture. Thromb Res 1994;94:317-26.

Goetzl EJ, Dolezalova H, Kong Y, Zeng L. Dual mechanisms for lysophospholipid induction of proliferation of human breast carcinoma cells. Cancer Res 1999;59:4732-7.

Imamura F, Mukai M, Ayaki M, et al. Involvement of small GTPases Rho and Rac in the invasion of rat ascites hepatoma cells. Clin Exp Metastasis 1999;17:141-8.

Genda T, Sakamoto M, Ichida T, et al. Cell motility mediated by rho and Rho-associated protein kinase plays a critical role in intrahepatic metastasis of human hepatocellular carcinoma. Hepatology 1999;30:1027-36.

Manning TJ Jr, Parker JC, Sontheimer H. Role of lysophosphatidic acid and rho in glioma cell motility. Cell Motil Cytoskeleton 2000;45:185-199.

Mukai M, Imamura F, Ayaki M, et al. Inhibition of tumor invasion and metastasis by a novel lysophosphatidic acid (cyclic LPA). Int J Cancer 1999;81:918-22.

Panetti TS, Chen H, Misenheimer TM, Getzler SB, Mosher DF. Endothelial cell mitogenesis induced by LPA: inhibition by thrombospondin-1 and thrombospondin-2. J Lab Clin Med 1997;129:208-16.

Ren XD, Kiosses WB, Schwartz MA. Regulation of the small GTP-binding protein Rho by cell adhesion and the cytoskeleton. EMBO J 1999;18:578-85.

Sengupta S, Xiao Y, Xu Y. A novel laminin-induced LPA autocrine loop in the migration of ovarian cancer cells. FASEB J 2003;11:1570-2.

Xiao Y, Chen Y, Kennedy AW, Belinson J, Xu Y. Evaluation of plasma lysophospholipids for diagnostic significance using electrospray ionization mass spectrometry (ESI-MS) analyses. Ann NY Acad Sci 2000;905:242-59.

Liscovitch M, Cantley LC. Lipid second messengers. Cell 1994;77:329-34.

Moolenaar WH, Kranenburg O, Postma FR, Zondag GC. Lysophosphatidic acid: G-protein signaling and cellular responses. Curr Opin Cell Biol 1997;9:168-73.

Shen Z, Wu M, Elson P, et al. Fatty acid composition of lysophosphatidic acid and lysophosphatidylinositol in plasma from patients with ovarian cancer and other gynecological diseases. Gynecol Oncol 2001;83:25-30.

Okita M, Gaudette DC, Mills GB, Holub BJ. Elevated levels and altered fatty acid composition of plasma lysophosphatidylcholine(lysoPC) in ovarian cancer patients. Int J Cancer 1997;71:31-4.

Van Brocklyn JR, Lee MJ, Menzeleev R, et al. Dual actions of sphingosine-1-phosphate: extracellular through the Gi-coupled receptor Edg-1 and intracellular to regulate proliferation and survival. J Cell Biol 1998;142:229-40.

Spiegel S, Milstien S. Sphingolipid metabolites: members of a new class of lipid second messengers. J Membr Biol 1995;146:225-37.

Meyer zu Heringdorf D, van Koppen CJ, Jakobs KH. Molecular diversity of sphingolipid signaling. FEBS Lett 1997;410:34-8.

Spiegel S. Sphingosine 1-phosphate: a prototype of a new class of second messengers. J Leukoc Biol 1999;65:341-4.

Ozols RF, Rubin SC, Thomas G, Robboy S. Epithelial ovarian cancer. In: Hoskins WJ, Perez CA, Young RC, editors. Principles and principles of gynecologic oncology. Philadelphia: Lippincott-Raven Publishers; 1997. p. 958.

WHO. WHO Handbook for reporting results of cancer treatment. Geneva (Switzerland): WHO; 1979.

Xiao YJ, Schwartz B, Washington M, et al. Electrospray ionization mass spectrometry analysis of lysophospholipids in human ascitic fluids: comparison of the lysophospholipid contents in malignant vs nonmalignant ascitic fluids. Anal Biochem 2001;290:302-13.

Zweig MH, Campbell G. Receiver-operating characteristic (ROC) plots: a fundamental evaluation tool in clinical medicine. Clin Chem 1993;39:561-77.

Jacobs IJ, Skates SJ, MacDonald N, et al. Screening for ovarian cancer: a pilot randomized controlled trial. Lancet 1999;353:1207-10.

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Thông tin xuất bản

Cancer Epidemiology Biomarkers and Prevention

Tập 13 Số 7

1185-1191

Thông tin tác giả