Taiwanese Journal of Obstetrics and Gynecology
Volume 45, Issue 1 , Pages 26-32, March 2006

Seldi-tof MS Profiling of Plasma Proteins in Ovarian Cancer

  • Shao-Pai Wu

      Affiliations

    • Department of Obstetrics and Gynecology, Army Forces Tao-Yuan General Hospital, Tao-Yuan, Taipei, Taiwan
  • ,
  • Ya-Wen Lin

      Affiliations

    • Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan
  • ,
  • Hung-Cheng Lai

      Affiliations

    • Department of Obstetrics and Gynecology, Tri-Service General Hospital, Taipei, Taiwan
  • ,
  • Tang-Yuan Chu

      Affiliations

    • Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan
    • Department of Obstetrics and Gynecology, Tri-Service General Hospital, Taipei, Taiwan
  • ,
  • Yu-Liang Kuo

      Affiliations

    • Department of Obstetrics and Gynecology, Army Forces Tao-Yuan General Hospital, Tao-Yuan, Taipei, Taiwan
  • ,
  • Hang-Seng Liu

      Affiliations

    • Department of Obstetrics and Gynecology, Army Forces Tao-Yuan General Hospital, Tao-Yuan, Taipei, Taiwan
    • Corresponding Author InformationCorrespondence to: Dr. Hang-Seng Liu, Department of Obstetrics and Gynecology, Army Forces Tao-Yuan General Hospital, 168 Chong-Shin Road, Lungtan Tao-Yuan County 325, Taiwan

Received 14 July 2005; received in revised form 19 July 2005; accepted 19 July 2005.

Article Outline

Summary 

Objective

Proteomic profiling of plasma or serum is a technique to identify new biomarkers in disease. The objective of this study was to identify new plasma biomarkers in ovarian cancer patients using mass spectrometry protein profiling and artificial intelligence.

Methods

A total of 65 plasma samples obtained from women with ovarian cancer (n = 35) and age-matched disease-free controls (n = 30) were applied to anion exchange protein chips for protein profiling by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS).

Results

SELDI-TOF MS was highly reproducible in detecting ovarian tumor-specific protein profiles. One protein peak (relative molecular mass, Mr, 11,537 Da) was identified in plasma from women with ovarian cancer but not in controls. Two peaks, Mr 5,147 and 8,780 Da, were present in the plasma of controls but not of women with ovarian cancer. After a training analysis, classification analysis generated by univariant or linear combination split was performed to reach a discriminant protein signature pattern. After cross validation, a sensitivity of 84% and specificity of 89% for all studied cases and controls was reached.

Conclusion

This study clearly demonstrates that the combined technology of SELDI-TOF MS and artificial intelligence is effective in distinguishing protein expression between normal and ovarian cancer plasma. The identified protein peaks may be candidate proteins for early detection of ovarian cancer or evaluation of therapeutic response.

Key Words:  protein chip , ovarian cancer , SELDI-TOF mass spectrometry

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References 

  1. Farias-Eisner R, Teng F, Oliveira M, Leuchter R, Karlan B, Lagasse LD, et al. The influence of tumor grade, distribution, and extent of carcinomatosis in minimal residual stage III epithelial ovarian cancer after optimal primary cytoreductive surgery . Gynecol Oncol . 1994;55:108–110
  2. Farias-Eisner R , Kim YB , Berek JS . Surgical management of ovarian cancer . Semin Surg Oncol . 1994;10:268–275
  3. Jacobs IJ , Skates SJ , MacDonald N , et al.   Screening for ovarian cancer: a pilot randomised controlled trial . Lancet . 1999;353:1207–1210
  4. Jacobs IJ , Menon U . Progress and challenges in screening for early detection of ovarian cancer . Mol Cell Proteomics . 2004;3:355–366
  5. Menon U , Jacobs IJ . Recent developments in ovarian cancer screening . Curr Opin Obstet Gynecol . 2000;12:39–42
  6. Cohen LS , Escobar PF , Scharm C , Glimco B , Fishman DA . Three-dimensional power Doppler ultrasound improves the diagnostic accuracy for ovarian cancer prediction . Gynecol Oncol . 2001;82:40–48
  7. Ye B , Cramer DW , Skates SJ , et al.   Haptoglobin-alpha subunit as potential serum biomarker in ovarian cancer: identification and characterization using proteomic profiling and mass spectrometry . Clin Cancer Res . 2003;9:2904–2911
  8. Bast RC , Klug TL , St John E , et al.   A radioimmunoassay using a monoclonal antibody to monitor the course of epithelial ovarian cancer . N Engl J Med . 1983;309:883–887
  9. 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;93:1458–1464
  10. Kim JH , Skates SJ , Uede T , et al.   Osteopontin as a potential diagnostic biomarker for ovarian cancer . JAMA . 2002;287:1671–1679
  11. Schummer M , Ng WV , Bumgarner RE , et al.   Comparative hybridization of an array of 21,500 ovarian cDNAs for the discovery of genes overexpressed in ovarian carcinomas . Gene . 1999;238:375–385
  12. Petricoin EF , Ardekani AM , Hitt BA , et al.   Use of proteomic patterns in serum to identify ovarian cancer . Lancet . 2002;359:572–577
  13. Espina V , Dettloff KA , Cowherd S , Petricoin EF , Liotta LA . Use of proteomic analysis to monitor responses to biological therapies . Expert Opin Biol Ther . 2004;4:83–93
  14. Vlahou A , Laronga C , Wilson L , et al.   A novel approach toward development of a rapid blood test for breast cancer . Clin Breast Cancer . 2003;4:203–209
  15. Chu TY , Hwang KS , Yu MH , Lee HS , Lai HC , Liu JY . A research-based tumor tissue bank of gynecologic oncology: characteristics of nucleic acids extracted from normal and tumor tissues from different sites . Int J Gynecol Cancer . 2002;12:171–176
  16. Diamandis EP . Analysis of serum proteomic patterns for early cancer diagnosis: drawing attention to potential problems . J Natl Cancer Inst . 2004;96:353–356
  17. Laronga C , Becker S , Watson P , et al.   SELDI-TOF serum profiling for prognostic and diagnostic classification of breast cancers . Dis Markers . 2003;19:229–238
  18. Lehrer S , Roboz J , Ding H , et al.   Putative protein markers in the sera of men with prostatic neoplasms . BJU Int . 2003;92:223–225
  19. Grizzle WE , Adam BL , Bigbee WL , et al.   Serum protein expression profiling for cancer detection: validation of a SELDI-based approach for prostate cancer . Dis Markers . 2003;19:185–195
  20. Issaq HJ , Veenstra TD , Conrads TP , Felschow D . The SELDITOF MS approach to proteomics: protein profiling and biomarker identification . Biochem Biophys Res Commun . 2002;292:587–592
  21. Ebert MP , Meuer J , Wiemer JC , et al.   Identification of gastric cancer patients by serum protein profiling . J Proteome Res . 2004;3:1261–1266
  22. Rodland KD . Proteomics and cancer diagnosis: the potential of mass spectrometry . Clin Biochem . 2004;37:579–583
  23. Verma M , Wright GL , Hanash SM , Gopal-Srivastava R , Srivastava S . Proteomic approaches within the NCI early detection research network for the discovery and identification of cancer biomarkers . Ann N Y Acad Sci . 2001;945:103–115
  24. Wilson LL , Tran L , Morton DL , Hoon DS . Detection of differentially expressed proteins in early-stage melanoma patients using SELDI-TOF mass spectrometry . Ann N Y Acad Sci . 2004;1022:317–322
  25. Wright GL . SELDI proteinchip MS: a platform for biomarker discovery and cancer diagnosis . Expert Rev Mol Diagn . 2002;2:549–563
  26. Wulfkuhle JD , Paweletz CP , Steeg PS , Petricoin EF , Liotta L . Proteomic approaches to the diagnosis, treatment, and monitoring of cancer . Adv Exp Med Biol . 2003;532:59–68
  27. Xiao Z , Prieto D , Conrads TP , Veenstra TD , Issaq HJ . Proteomic patterns: their potential for disease diagnosis . Mol Cell Endocrinol . 2005;230:95–106
  28. Yang EC , Guo J , Diehl G , et al.   Protein expression profiling of endometrial malignancies reveals a new tumor marker: chaperonin 10 . J Proteome Res . 2004;3:636–643
  29. Zhu XD , Zhang WH , Li CL , Xu Y , Liang WJ , Tien P . New serum biomarkers for detection of HBV-induced liver cirrhosis using SELDI protein chip technology . World J Gastroenterol . 2004;10:2327–2329
  30. Yu JK , Chen YD , Zheng S . An integrated approach to the detection of colorectal cancer utilizing proteomics and bioinformatics . World J Gastroenterol . 2004;10:3127–3131
  31. Kozak KR , Amneus MW , Pusey SM , et al.   Identification of biomarkers for ovarian cancer using strong anion-exchange ProteinChips: potential use in diagnosis and prognosis . Proc Natl Acad Sci USA . 2003;100:12343–12348
  32. Zhang Z , Bast RC , Yu Y , et al.   Three biomarkers identified from serum proteomic analysis for the detection of early stage ovarian cancer . Cancer Res . 2004;64:5882–5890
  33. Vehmas AK , Borchelt DR , Price DL , et al.   beta-Amyloid peptide vaccination results in marked changes in serum and brain Abeta levels in APPswe/PS1DeltaE9 mice, as detected by SELDI-TOF-based ProteinChip technology . DNA Cell Biol . 2001;20:713–721
  34. Austen BM , Frears ER , Davies H . The use of SELDI proteinchip arrays to monitor production of Alzheimer's beta-amyloid in transfected cells . J Pept Sci . 2000;6:459–469
  35. Davies H , Lomas L , Austen B . Profiling of amyloid beta peptide variants using SELDI protein chip arrays . Biotechniques . 1999;27:1258–1261
  36. Ganz T . Immunology. Versatile defensins . Science . 2002;298:977–979

PII: S1028-4559(09)60186-8

doi:10.1016/S1028-4559(09)60186-8

Taiwanese Journal of Obstetrics and Gynecology
Volume 45, Issue 1 , Pages 26-32, March 2006