Prospect for a new timely ovarian cancer diagnostic procedure based on the use of a combination of serum A-SAA and CA125 proteins


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Abstract

Objective. To study possibilities for enhancing the efficiency of minimally invasive diagnosis of ovarian cancer, by using a combination of serum A-SAA and CA-125 proteins detectable by mass spectrometry and enzyme immunoassay. Subjects and methods. Clinical and morphological data on examinees and their sera were explored. The study sample consisted of 91 patients, which was divided into 4 comparable groups: 1) 34 patients with ovarian cancer; 2) 14 with benign ovarian tumors; 3) 17 with uterine myoma; 4) 26 apparently healthy women. A Labsystems Multitiskan Plus spectrophotometer (Finland) was used to determine A-SAA and CA-125 concentrations. Results. The investigation has shown that SELDI-TOF mass spectrometry may be rather highly effective in recognizing the sera of patients with ovarian cancer, benign ovarian tumors, or uterine myoma and healthy women. The basis for the developed experimental diagnostic system was mass spectrometric data that could individually provide about 90% diagnostic accuracy. The concurrent use of mass spectrometric data and A-SAA and CA-125 concentrations measured by enzyme immunoassay caused an increase in diagnostic accuracy up to 95.2%. The use of the support vector method yielded the best results. The merit of our proposed profiling method is its simplicity. The absence of serum prefractionation steps leads to more reproducible results and increases chances of introducing the methods into practical diagnosis. The findings may serve as prerequisites for developing a special hardware and software complex for the timely diagnosis of ovarian cancer. Conclusion. Thus, A-SAA as an independent ovarian cancer marker detectable by SELDI-TOF mass spectrometry has a sensitivity of 50% and a specificity of 96.4%. One important point to remember is that addition of A-SAA and CA-125 concentrations measurable by enzyme immunoassay to A-SAA spectrometric data allows the diagnostic accuracy for ovarian cancer to be increased up to 95%.

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About the authors

O. V Makarov

N.I. Pirogov Russian National Research Medical University, Ministry of Health of Russia

Email: profmakarov@mail.ru
professor, Department of Obstetrics and Gynaecology, Medical Faculty

S. A Moshkovsky

V.N. Orekhovich Research Institute of Biomedical Chemistry, Russian Academy of Medical Sciences

Email: smosh@mail.ru
Sc.D., Head of the Laboratory of Medicinal Proteomics

M. A Karpova

V.N. Orekhovich Research Institute of Biomedical Chemistry, Russian Academy of Medical Sciences

Email: moushutic@mail.ru
researcher of the Laboratory of Medicinal Proteomics

M. R Narimanova

N.I. Pirogov Russian National Research Medical University, Ministry of Health of Russia

Email: safarovametanat@ya.ru
assistant of the Department of Obstetrics and Gynaecology, Medical Faculty

References

  1. Аксель Е.М. Статистика злокачественных новообразований женских половых органов. В кн.: Козаченко В.П., ред. Клиническая онкогинекология. М.: Медицина; 2005: 9-17. [Aksel E.M. Statistics malignant neoplasms of female genital mutilation. In: Kozachenko V.P., ed. Clinical cancers. M.: Meditsina; 2005: 9-17. (in Russian)]
  2. Jacobs I.J., Menon U. Progress and challenges in screening for early detection of ovarian cancer. Mol. Cell. Proteomics. 2004; 3(4): 355-66.
  3. Petricoin E.F., Ardekani A.M., Hitt B.A., Levine PJ., Fusaro V.A., Steinberg S.M. et al. Use of proteomic patterns in serum to identify ovarian cancer. Lancet. 2002; 359(9306): 572-7.
  4. Адамян Л.В., Жордания К.И., Белобородов С.М. Репродуктивная функция у онкологических больных. Как сохранить возможность иметь детей. Вопросы онкологии. 2004; 50(3): 279-93. [Adamyan L.V., Zhordaniya K.I., Beloborodov S.M. Reproductive function in cancer patients. How to maintain the ability to have children. Voprosyi onkologii. 2004; 50(3): 279-93. (in Russian)]
  5. Жорданиа К.И. Новый взгляд на этиопатогенез рака яичников. Онкологинекология. 2012; 3: 4-9. [Zhordania K.I. A new look at the etiopathogenesis of ovarian cancer. Onkologinekologiya. 2012; 3: 4-9. (in Russian)]
  6. Адамян Л.В., Фанченко Н.Д., Алексеева М.Л., Новикова E.H., Андреева E.H. Диагностическая значимость определения онкомаркеров СА 125, СА 19,9, СЕА в гинекологии. Методические рекомендации. М.; 1994. [Adamyan L.V., Fanchenko N.D., Alekseeva M.L., Novikova E.H., Andreeva E.H. Diagnostic value of determination of tumor markers CA 125, CA 19.9, CEA in gynecology. Methodical recommendations. M.; 1994. (in Russian)]
  7. Zhang Z., Bast R.C. Jr, Yu Y., Li J., Sokoll L.J., Rai A.J. et al. Three biomarkers identified from serum proteomic analysis for the detection of early stage ovarian cancer. Cancer Res. 2004; 64(16): 5882-90.
  8. Торопыгин И.Ю., Серебрякова М.В., Хряпова Е.В., Миргородская О.А. Использование неполного протеолиза плазмы крови в диагностике рака яичника. В кн.: Материалы докладов VI гампозиума «Химия протеолитических ферментов». М.; 2007: 65. [Toropygin I.Yu., Serebryakova M.V., Hryapova E.V., Mirgorodskaya O.A. Using partial proteolysis in blood plasma of ovarian cancer diagnosis. In: Proceedings of the Symposium VI „Chemistry of proteolytic enzymes.” M.; 2007: 65. (in Russian)]
  9. Gutfeld O., Prus D., Ackerman Z., Dishon S., Linke R.P., Levin M., Urieli-Shoval S. Expression of serum amyloid A, in normal, dysplastic, and neoplastic human colonic mucosa: implication for a role in colonic tumorigenesis. J. Histochem. Cytochem. 2006; 54: 63-73.
  10. Kovacevic A., Hammer A., Sundl M., Pfister B., Hrzenjak A., Ray A. et al. Expression of serum amyloid A transcripts in human trophoblast and fetal-derived trophoblast-like choriocarcinoma cells. FEBS Lett. 2006; 580: 161-7.
  11. He R., Sang H., Ye R.D. Serum amyloid A induces IL-8 secretion through a G protein-coupled receptor, FPRL1/LXA4R. Blood. 2003; 101(4): 1572-81.
  12. Lee H.Y., Kim M.K., Park K.S., Bae Y.H., Yun J., Park J.I. et al. Serum amyloid A stimulates matrix-metalloproteinase-9 upregulation via formyl peptide receptor like-1-mediated signaling in human monocytic cells. Biochem. Biophys. Res. Commun. 2005; 330(3): 989-98.
  13. O’Hara R., Murphy E.P., Whitehead A.S., FitzGerald O., Bresnihan B. Acute-phase serum amyloid A production by rheumatoid arthritis synovial tissue. Arthritis Res. 2000; 2(2): 142-4.
  14. Wulfkuhle J.D., Liotta L.A., Petricoin E.F. Proteomic applications for the early detection of cancer. Nat. Rev. Cancer. 2003; 3(4): 267-75.
  15. Le L., Chi K., Tyldesley S., Flibotte S., Diamond D.L., Kuzyk M.A., Sadar M.D. Identification of serum amyloid A as a biomarker to distinguish prostate cancer patients with bone lesions. Clin. Chem. 2005; 51(4): 695-707.
  16. Mao Y., Zhou X.B., Pi D.Y., Sun Y.X. Constructing support vector machine ensembles for cancer classification based on proteomic profiling. Genomics Proteomics Bioinformatics. 2005; 3(4): 238-41.
  17. Skates S.J., Horick N., Yu Y., Xu F.J., Berchuck A., Havrilesky L.J. et al. Preoperative sensitivity and specificity for early-stage ovarian cancer when combining cancer antigen CA-125II, CA 15-3, CA 72-4, and macrophage colony-stimulating factor using mixtures of multivariate normal distributions. J. Clin. Oncol. 2004; 22(20): 4059-66.
  18. Vapnik V.N. Statistical learning theory. New York: Springer-Verlag; 1998.
  19. Xu L., Tan A.C., Naiman D.Q., Geman D., Winslow R.L. Robust prostate cancer marker genes emerge from direct integration of inter-study microarray data. Bioinformatics. 2005; 21(20): 3905-11.
  20. Uhlar C.M., Whitehead A.S. Serum amyloid A, the major vertebrate acute-phase reactant. Eur. J. Biochem. 1999; 265(2): 501-23.
  21. Casl M.T., Coen D., Simic D. Serum amyloid A protein in the prediction of postburn complications and fatal outcome in patients with severe burns. Eur. J. Clin. Chem. Clin. Biochem. 1996; 34(1): 31-5.
  22. Casl M.T., Surina B., Gojnaric-Spasic I., Pape E., Jagarinec N., Kranjcevic S. Serum amyloid A protein in patients with acute myocardial infarction. Ann. Clin. Biochem. 1995; 32(2): 196-200.
  23. Gericke B., Raila J., Sehouli J., Haebel S., Konsgen D., Mustea A., Schweigert F.J. Microheterogeneity of transthyretin in serum and ascitic fluid of ovarian cancer patients. BMC Cancer. 2005; 5: 133.

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