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Int J Proteomics. 2014;2014:129064. doi: 10.1155/2014/129064. Epub 2014 Jun 15.

Prediction of spontaneous regression of cervical intraepithelial neoplasia lesions grades 2 and 3 by proteomic analysis.

International journal of proteomics

Kai-Erik Uleberg, Irene Tveiterås Ovestad, Ane Cecilie Munk, Cato Brede, Bianca van Diermen, Einar Gudlaugsson, Emiel A M Janssen, Anne Hjelle, Jan P A Baak

Affiliations

  1. Norconsult AS, Section 355 QA Service, P.O. Box 216, NO-4503 Mandal, Norway ; Former International Research Institute of Stavanger (IRIS), P.O. Box 8046, 4068 Stavanger, Norway.
  2. Pathology Department, Stavanger University Hospital, P.O. Box 8100, 4068 Stavanger, Norway.
  3. Department of Gynecology and Obstetrics, Stavanger University Hospital, P.O. Box 8100, 4068 Stavanger, Norway.
  4. Department of Medical Biochemistry, Stavanger University Hospital, P.O. Box 8100, 4068 Stavanger, Norway.
  5. Former International Research Institute of Stavanger (IRIS), P.O. Box 8046, 4068 Stavanger, Norway ; Mediteam AS, Sjøveien 34, 4315 Sandnes, Norway.
  6. Pathology Department, Stavanger University Hospital, P.O. Box 8100, 4068 Stavanger, Norway ; The Gade Institute, University of Bergen, P.O. Box 1400, 5021 Bergen, Norway.

PMID: 25018881 PMCID: PMC4082862 DOI: 10.1155/2014/129064

Abstract

Regression of cervical intraepithelial neoplasia (CIN) 2-3 to CIN 1 or less is associated with immune response as demonstrated by immunohistochemistry in formaldehyde-fixed paraffin-embedded (FFPE) biopsies. Proteomic analysis of water-soluble proteins in supernatants of biopsy samples with LC-MS (LTQ-Orbitrap) was used to identify proteins predictive of CIN2-3 lesions regression. CIN2-3 in the biopsies and persistence (CIN2-3) or regression (≤CIN1) in follow-up cone biopsies was validated histologically by two experienced pathologists. In a learning set of 20 CIN2-3 (10 regressions and 10 persistence cases), supernatants were depleted of seven high abundance proteins prior to unidimensional LC-MS/MS protein analysis. Mean protein concentration was 0.81 mg/mL (range: 0.55-1.14). Multivariate statistical methods were used to identify proteins that were able to discriminate between regressive and persistent CIN2-3. The findings were validated in an independent test set of 20 CIN2-3 (10 regressions and 10 persistence cases). Multistep identification criteria identified 165 proteins. In the learning set, zinc finger protein 441 and phospholipase D6 independently discriminated between regressive and persistent CIN2-3 lesions and correctly classified all 20 patients. Nine regression and all persistence cases were correctly classified in the validation set. Zinc finger protein 441 and phospholipase D6 in supernatant samples detected by LTQ-Orbitrap can predict regression of CIN2-3.

References

  1. Cell Oncol (Dordr). 2011 Oct;34(5):443-50 - PubMed
  2. Anal Chem. 2009 Apr 1;81(7):2581-90 - PubMed
  3. Traffic. 2008 Aug;9(8):1233-9 - PubMed
  4. Biochem Cell Biol. 2004 Feb;82(1):225-53 - PubMed
  5. Cancer Lett. 2008 Aug 8;266(2):135-43 - PubMed
  6. CA Cancer J Clin. 2011 Mar-Apr;61(2):69-90 - PubMed
  7. PLoS One. 2013;8(2):e56633 - PubMed
  8. Drug Discov Today. 2005 May 15;10(10):719-25 - PubMed
  9. Biochem Biophys Res Commun. 2004 Jul 16;320(1):45-53 - PubMed
  10. J Clin Pathol. 2006 Oct;59(10):1017-28 - PubMed
  11. Int J Gynecol Pathol. 1993 Apr;12(2):186-92 - PubMed
  12. Arch Pathol Lab Med. 2001 Sep;125(9):1200-3 - PubMed
  13. Nature. 2012 Nov 8;491(7423):284-7 - PubMed
  14. Nucleic Acids Symp Ser (Oxf). 2008;(52):185-6 - PubMed
  15. Exp Ther Med. 2013 Dec;6(6):1365-1368 - PubMed
  16. Proteome Sci. 2011 Jun 28;9:36 - PubMed
  17. Mol Cancer Res. 2003 Sep;1(11):789-800 - PubMed
  18. Int J Oncol. 2013 Dec;43(6):1754-62 - PubMed
  19. Methods Mol Med. 2005;119:85-99 - PubMed
  20. APMIS. 2007 Dec;115(12):1409-14 - PubMed
  21. Int J Gynecol Pathol. 2004 Apr;23(2):100-9 - PubMed
  22. Cold Spring Harb Symp Quant Biol. 2008;73:273-81 - PubMed
  23. Aust N Z J Obstet Gynaecol. 2010 Aug;50(4):363-70 - PubMed
  24. Genes Dev. 2006 Aug 1;20(15):1993-7 - PubMed
  25. Biochim Biophys Acta. 2009 Sep;1791(9):845-9 - PubMed
  26. PLoS One. 2012;7(3):e33711 - PubMed
  27. Proteome Sci. 2009 Apr 17;7:17 - PubMed
  28. Cell Mol Life Sci. 2001 Apr;58(4):625-35 - PubMed
  29. Cancer Epidemiol Biomarkers Prev. 2002 May;11(5):483-8 - PubMed
  30. Mol Oncol. 2007 Sep;1(2):144-59 - PubMed
  31. Epigenetics. 2014 Jan;9(1):113-8 - PubMed
  32. Prog Mol Biol Transl Sci. 2010;96:133-56 - PubMed
  33. Cochrane Database Syst Rev. 2010 Jun 16;(6):CD001318 - PubMed
  34. Pathol Res Pract. 2010 Sep 15;206(9):591-601 - PubMed
  35. J Proteome Res. 2010 Jul 2;9(7):3608-20 - PubMed
  36. J Biol Chem. 2011 Mar 4;286(9):7279-89 - PubMed
  37. Virology. 2009 Feb 20;384(2):260-5 - PubMed
  38. Mod Pathol. 2010 Sep;23(9):1231-40 - PubMed
  39. BMB Rep. 2010 Sep;43(9):635-41 - PubMed
  40. Genome Biol. 2003;4(10):231 - PubMed
  41. Lancet. 2006 Feb 11;367(9509):489-98 - PubMed
  42. Cell Biochem Biophys. 2008;50(3):111-31 - PubMed
  43. Curr Opin Struct Biol. 2001 Feb;11(1):39-46 - PubMed
  44. J Clin Pathol. 2011 Apr;64(4):303-7 - PubMed
  45. BMC Infect Dis. 2009 Jul 29;9:119 - PubMed
  46. Mod Pathol. 1998 Sep;11(9):886-91 - PubMed
  47. PLoS One. 2011;6(7):e22727 - PubMed
  48. Gynecol Oncol. 2012 Dec;127(3):489-94 - PubMed
  49. Nature. 2012 Nov 8;491(7423):279-83 - PubMed
  50. JAMA. 2004 May 5;291(17):2100-6 - PubMed
  51. Am J Clin Pathol. 2004 Dec;122(6):902-11 - PubMed

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