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Ovarian Cancer: Biomarker Proteomic Diagnosis in Progress

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Abstract

Ovarian cancer lacks clear syndromes at an early stage and could result in serious problem in woman's health status. The current diagnostic approach relies on physical examination, ultrasound examination, and blood test for CA125. These approaches could not diagnose early stage ovarian cancer with high sensitivity and specificity. The present paper reviewed the efforts in screening the proteomic biomarkers for ovarian cancer. The sources of biomarkers were discussed. Then, the current techniques in proteomics were introduced. Finally, the biomarkers for ovarian cancer were summarized.

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References

  1. Andersen, M. R., Goff, B. A., Lowe, K. A., Scholler, N., Bergan, L., Drescher, C. W., Paley, P., & Urban, N. (2010). Use of a symptom index, CA125, and HE4 to predict ovarian cancer. Gynecologic Oncology, 116, 378–383.

    Article  Google Scholar 

  2. Anderson, G. L. (2010). Ovarian cancer biomarker screening: still too early to tell. Women’s Health (London, England), 6, 487–490.

    Article  Google Scholar 

  3. Anderson, G. L., McIntosh, M., Wu, L., Barnett, M., Goodman, G., Thorpe, J. D., Bergan, L., Thornquist, M. D., Scholler, N., Kim, N., O’Briant, K., Drescher, C., & Urban, N. (2010). Assessing lead time of selected ovarian cancer biomarkers: a nested case–control study. Journal of the National Cancer Institute, 102, 26–38.

    Article  CAS  Google Scholar 

  4. Badgwell, D., Lu, Z., Cole, L., Fritsche, H., Atkinson, E. N., Somers, E., Allard, J., Moore, R. G., Lu, K. H., & Bast, R. C., Jr. (2007). Urinary mesothelin provides greater sensitivity for early stage ovarian cancer than serum mesothelin, urinary hCG free beta subunit and urinary hCG beta core fragment. Gynecologic Oncology, 106, 490–497.

    Article  CAS  Google Scholar 

  5. Bast, R. C., Jr., Badgwell, D., Lu, Z., Marquez, R., Rosen, D., Liu, J., Baggerly, K. A., Atkinson, E. N., Skates, S., Zhang, Z., Lokshin, A., Menon, U., Jacobs, I., & Lu, K. (2005). New tumor markers: CA125 and beyond. International Journal of Gynecological Cancer, 15(Suppl 3), 274–281.

    Article  Google Scholar 

  6. Brioschi, P. A., Bischof, P., Rapin, C., De Roten, M., Irion, O., & Krauer, F. (1985). Longitudinal study of CEA and CA125 in ovarian cancer. Gynecologic Oncology, 21, 1–6.

    Article  CAS  Google Scholar 

  7. Cadron, I., Van Gorp, T., Amant, F., Vergote, I., Moerman, P., Waelkens, E., Daemen, A., Van De Plas, R., De Moor, B., & Zeillinger, R. (2009). The use of laser microdissection and SELDI-TOF MS in ovarian cancer tissue to identify protein profiles. Anticancer Research, 29, 1039–1045.

    Google Scholar 

  8. Cadron, I., Van Gorp, T., Moerman, P., Waelkens, E., & Vergote, I. (2011). Proteomic analysis of laser microdissected ovarian cancer tissue with SELDI-TOF MS. Methods in Molecular Biology, 755, 155–163.

    Article  Google Scholar 

  9. Colakovic, S., Lukic, V., Mitrovic, L., Jelic, S., Susnjar, S., & Marinkovic, J. (2000). Prognostic value of CA125 kinetics and half-life in advanced ovarian cancer. The International Journal of Biological Markers, 15, 147–152.

    CAS  Google Scholar 

  10. Court, M., Selevsek, N., Matondo, M., Allory, Y., Garin, J., Masselon, C. D., & Domon, B. (2011). Toward a standardized urine proteome analysis methodology. Proteomics, 11, 1160–1171.

    Article  CAS  Google Scholar 

  11. Cruickshank, D. J., Terry, P. B., & Fullerton, W. T. (1992). CA125-response assessment in epithelial ovarian cancer. International Journal of Cancer, 51, 58–61.

    Article  CAS  Google Scholar 

  12. Dijkstra, M., Vonk, R. J., & Jansen, R. C. (2007). SELDI-TOF mass spectra: a view on sources of variation. Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences, 847, 12–23.

    Article  CAS  Google Scholar 

  13. Duffy, M. J., Bonfrer, J. M., Kulpa, J., Rustin, G. J., Soletormos, G., Torre, G. C., Tuxen, M. K., & Zwirner, M. (2005). CA125 in ovarian cancer: European Group on Tumor Markers guidelines for clinical use. International Journal of Gynecological Cancer, 15, 679–691.

    Article  CAS  Google Scholar 

  14. Gortzak-Uzan, L., Ignatchenko, A., Evangelou, A. I., Agochiya, M., Brown, K. A., St Onge, P., Kireeva, I., Schmitt-Ulms, G., Brown, T. J., Murphy, J., Rosen, B., Shaw, P., Jurisica, I., & Kislinger, T. (2008). A proteome resource of ovarian cancer ascites: integrated proteomic and bioinformatic analyses to identify putative biomarkers. Journal of Proteome Research, 7, 339–351.

    Article  CAS  Google Scholar 

  15. Gustafsson, J. O., Oehler, M. K., Ruszkiewicz, A., McColl, S. R., & Hoffmann, P. (2011). MALDI imaging mass spectrometry (MALDI-IMS)-application of spatial proteomics for ovarian cancer classification and diagnosis. International Journal of Molecular Sciences, 12, 773–794.

    Article  CAS  Google Scholar 

  16. Hellstrom, I., Heagerty, P. J., Swisher, E. M., Liu, P., Jaffar, J., Agnew, K., & Hellstrom, K. E. (2010). Detection of the HE4 protein in urine as a biomarker for ovarian neoplasms. Cancer Letters, 296, 43–48.

    Article  CAS  Google Scholar 

  17. Henderson, N. A., & Steele, R. J. (2005). SELDI-TOF proteomic analysis and cancer detection. The Surgeon, 3(383–390), 422.

    Google Scholar 

  18. Imai, S., Maeda, H., Kiyozuka, Y., Noda, T., Moriyama, I., & Ichijo, M. (1989). Characterization of the CA125 antigen secreted from a newly established human ovarian cancer cell line (SHIN-3). Acta Pathologica Japonica, 39, 43–49.

    CAS  Google Scholar 

  19. Kim, K., Visintin, I., Alvero, A. B., & Mor, G. (2009). Development and validation of a protein-based signature for the detection of ovarian cancer. Clinics in Laboratory Medicine, 29, 47–55.

    Article  Google Scholar 

  20. Kohn, E. C., Azad, N., Annunziata, C., Dhamoon, A. S., & Whiteley, G. (2007). Proteomics as a tool for biomarker discovery. Disease Markers, 23, 411–417.

    CAS  Google Scholar 

  21. Kozak, K. R., Su, F., Whitelegge, J. P., Faull, K., Reddy, S., & Farias-Eisner, R. (2005). Characterization of serum biomarkers for detection of early stage ovarian cancer. Proteomics, 5, 4589–4596.

    Article  CAS  Google Scholar 

  22. Kuzuya, K., Nozaki, M., & Chihara, T. (1986). Evaluation of CA125 as a circulating tumor marker for ovarian cancer. Nihon Sanka Fujinka Gakkai Zasshi, 38, 949–957.

    CAS  Google Scholar 

  23. Larkin, S. E., Zeidan, B., Taylor, M. G., Bickers, B., Al-Ruwaili, J., Aukim-Hastie, C., & Townsend, P. A. (2010). Proteomics in prostate cancer biomarker discovery. Expert Review of Proteomics, 7, 93–102.

    Article  CAS  Google Scholar 

  24. Lemaire, R., Menguellet, S. A., Stauber, J., Marchaudon, V., Lucot, J. P., Collinet, P., Farine, M. O., Vinatier, D., Day, R., Ducoroy, P., Salzet, M., & Fournier, I. (2007). Specific MALDI imaging and profiling for biomarker hunting and validation: fragment of the 11S proteasome activator complex, Reg alpha fragment, is a new potential ovary cancer biomarker. Journal of Proteome Research, 6, 4127–4134.

    Article  CAS  Google Scholar 

  25. Lin, Y. W., Lin, C. Y., Lai, H. C., Chiou, J. Y., Chang, C. C., Yu, M. H., & Chu, T. Y. (2006). Plasma proteomic pattern as biomarkers for ovarian cancer. International Journal of Gynecological Cancer, 16(Suppl 1), 139–146.

    Article  Google Scholar 

  26. Liu, C. (2011). The application of SELDI-TOF-MS in clinical diagnosis of cancers. Journal of Biomedicine and Biotechnology, 2011, 245821.

    Google Scholar 

  27. Moore, R. G., McMeekin, D. S., Brown, A. K., DiSilvestro, P., Miller, M. C., Allard, W. J., Gajewski, W., Kurman, R., Bast, R. C., Jr., & Skates, S. J. (2009). A novel multiple marker bioassay utilizing HE4 and CA125 for the prediction of ovarian cancer in patients with a pelvic mass. Gynecologic Oncology, 112, 40–46.

    Article  CAS  Google Scholar 

  28. Moshkovskii, S. A., Serebryakova, M. V., Kuteykin-Teplyakov, K. B., Tikhonova, O. V., Goufman, E. I., Zgoda, V. G., Taranets, I. N., Makarov, O. V., & Archakov, A. I. (2005). Ovarian cancer marker of 11.7 kDa detected by proteomics is a serum amyloid A1. Proteomics, 5, 3790–3797.

    Article  CAS  Google Scholar 

  29. Moss, E. L., Hollingworth, J., & Reynolds, T. M. (2005). The role of CA125 in clinical practice. Journal of Clinical Pathology, 58, 308–312.

    Article  CAS  Google Scholar 

  30. Obermair, A. (2007). Preoperative serum CA125 in surgical stage 1 epithelial ovarian cancer. Gynecologic Oncology, 107, 357–358.

    Article  CAS  Google Scholar 

  31. Palmer, C., Duan, X., Hawley, S., Scholler, N., Thorpe, J. D., Sahota, R. A., Wong, M. Q., Wray, A., Bergan, L. A., Drescher, C. W., McIntosh, M. W., Brown, P. O., Nelson, B. H., & Urban, N. (2008). Systematic evaluation of candidate blood markers for detecting ovarian cancer. PLoS One, 3, e2633.

    Article  Google Scholar 

  32. Park, Y., Lee, J. H., Hong, D. J., Lee, E. Y., & Kim, H. S. (2011). Diagnostic performances of HE4 and CA125 for the detection of ovarian cancer from patients with various gynecologic and non-gynecologic diseases. Clinical Biochemistry, 44, 884–888.

    Article  CAS  Google Scholar 

  33. Petri, A. L., Simonsen, A. H., Hogdall, E., Christensen, I. J., Kjaer, S. K., Yip, C., Risum, S., Pedersen, A. T., Hartwell, D., Fung, E. T., & Hogdall, C. (2010). Comparison of proteomic biomarker panels in urine and serum for ovarian cancer diagnosis. Proteomics. Clinical Applications, 4, 304–314.

    Article  CAS  Google Scholar 

  34. Petri, A. L., Simonsen, A. H., Yip, T. T., Hogdall, E., Fung, E. T., Lundvall, L., & Hogdall, C. (2009). Three new potential ovarian cancer biomarkers detected in human urine with equalizer bead technology. Acta Obstetricia et Gynecologica Scandinavica, 88, 18–26.

    Article  CAS  Google Scholar 

  35. Plebani, M. (2005). Proteomics: the next revolution in laboratory medicine? Clinica Chimica Acta, 357, 113–122.

    Article  CAS  Google Scholar 

  36. Rosenthal, A. N., Menon, U., & Jacobs, I. J. (2006). Screening for ovarian cancer. Clinical Obstetrics and Gynecology, 49, 433–447.

    Article  Google Scholar 

  37. Roy, H. K., & Khandekar, J. D. (2007). Biomarkers for the early detection of cancer: an inflammatory concept. Archives of Internal Medicine, 167, 1822–1824.

    Article  Google Scholar 

  38. Shah, C. A., Lowe, K. A., Paley, P., Wallace, E., Anderson, G. L., McIntosh, M. W., Andersen, M. R., Scholler, N., Bergan, L. A., Thorpe, J. D., Urban, N., & Drescher, C. W. (2009). Influence of ovarian cancer risk status on the diagnostic performance of the serum biomarkers mesothelin, HE4, and CA125. Cancer Epidemiology, Biomarkers & Prevention, 18, 1365–1372.

    Article  CAS  Google Scholar 

  39. Steffensen, K. D., Waldstrom, M., Brandslund, I., & Jakobsen, A. (2011). Prognostic impact of prechemotherapy serum levels of HER2, CA125, and HE4 in ovarian cancer patients. International Journal of Gynecological Cancer, 21, 1040–1047.

    Article  Google Scholar 

  40. Tang, K. L., Li, T. H., Xiong, W. W., & Chen, K. (2010). Ovarian cancer classification based on dimensionality reduction for SELDI-TOF data. BMC Bioinformatics, 11, 109.

    Article  Google Scholar 

  41. Thomas, C. E., Sexton, W., Benson, K., Sutphen, R., & Koomen, J. (2010). Urine collection and processing for protein biomarker discovery and quantification. Cancer Epidemiology, Biomarkers & Prevention, 19, 953–959.

    Article  CAS  Google Scholar 

  42. Tiss, A., Timms, J. F., Smith, C., Devetyarov, D., Gentry-Maharaj, A., Camuzeaux, S., Burford, B., Nouretdinov, I., Ford, J., Luo, Z., Jacobs, I., Menon, U., Gammerman, A., & Cramer, R. (2010). Highly accurate detection of ovarian cancer using CA125 but limited improvement with serum matrix-assisted laser desorption/ionization time-of-flight mass spectrometry profiling. International Journal of Gynecological Cancer, 20, 1518–1524.

    Google Scholar 

  43. Tyson, D. R., & Ornstein, D. K. (2008). Proteomics of cancer of hormone-dependent tissues. Advances in Experimental Medicine and Biology, 630, 133–147.

    Article  CAS  Google Scholar 

  44. Van Gorp, T., Cadron, I., Despierre, E., Daemen, A., Leunen, K., Amant, F., Timmerman, D., De Moor, B., & Vergote, I. (2011). HE4 and CA125 as a diagnostic test in ovarian cancer: prospective validation of the risk of ovarian malignancy algorithm. British Journal of Cancer, 104, 863–870.

    Article  Google Scholar 

  45. Van Gorp, T., Cadron, I., & Vergote, I. (2011). The utility of proteomics in gynecologic cancers. Current Opinion in Obstetrics and Gynecology, 23, 3–7.

    Article  Google Scholar 

  46. Veenstra, T. D., Prieto, D. A., & Conrads, T. P. (2004). Proteomic patterns for early cancer detection. Drug Discovery Today, 9, 889–897.

    Article  CAS  Google Scholar 

  47. Vergote, I. B., Onsrud, M., Bormer, O. P., Sert, B. M., & Moen, M. (1992). CA125 in peritoneal fluid of ovarian cancer patients. Gynecologic Oncology, 44, 161–165.

    Article  CAS  Google Scholar 

  48. Wang, Q., Li, D., Zhang, W., Tang, B., Li, Q. Q., & Li, L. (2011). Evaluation of proteomics-identified CCL18 and CXCL1 as circulating tumor markers for differential diagnosis between ovarian carcinomas and benign pelvic masses. The International Journal of Biological Markers, 26(4), 262–273.

    Google Scholar 

  49. Whelan, L. C., Power, K. A., McDowell, D. T., Kennedy, J., & Gallagher, W. M. (2008). Applications of SELDI-MS technology in oncology. Journal of Cellular and Molecular Medicine, 12, 1535–1547.

    Article  CAS  Google Scholar 

  50. Wu, S. P., Lin, Y. W., Lai, H. C., Chu, T. Y., Kuo, Y. L., & Liu, H. S. (2006). SELDI-TOF MS profiling of plasma proteins in ovarian cancer. Taiwanese Journal of Obstetrics & Gynecology, 45, 26–32.

    Article  Google Scholar 

  51. Xiao, Z., Prieto, D., Conrads, T. P., Veenstra, T. D., & Issaq, H. J. (2005). Proteomic patterns: their potential for disease diagnosis. Molecular and Cellular Endocrinology, 230, 95–106.

    Article  CAS  Google Scholar 

  52. Yuan, Z., & Ghosh, D. (2008). Combining multiple biomarker models in logistic regression. Biometrics, 64, 431–439.

    Article  Google Scholar 

  53. Zhang, H., Kong, B., Qu, X., Jia, L., Deng, B., & Yang, Q. (2006). Biomarker discovery for ovarian cancer using SELDI-TOF-MS. Gynecologic Oncology, 102, 61–66.

    Article  CAS  Google Scholar 

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  1. The First Affiliated Hospital of Liaoning Medical University, Jinzhou 121001, Liaoning, China

    Yong Zhang, Bin Guo & Ran Bi

  2. Guta District People’s Street five No. two, Jinzhou 121000, Liaoning, China

    Ran Bi

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  1. Yong Zhang
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Zhang, Y., Guo, B. & Bi, R. Ovarian Cancer: Biomarker Proteomic Diagnosis in Progress. Appl Biochem Biotechnol 168, 910–916 (2012). https://doi.org/10.1007/s12010-012-9829-y

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