Table of Contents
International Journal of Proteomics
Volume 2014 (2014), Article ID 129064, 14 pages
http://dx.doi.org/10.1155/2014/129064
Research Article

Prediction of Spontaneous Regression of Cervical Intraepithelial Neoplasia Lesions Grades 2 and 3 by Proteomic Analysis

1Norconsult AS, Section 355 QA Service, P.O. Box 216, NO-4503 Mandal, Norway
2Former International Research Institute of Stavanger (IRIS), P.O. Box 8046, 4068 Stavanger, Norway
3Pathology Department, Stavanger University Hospital, P.O. Box 8100, 4068 Stavanger, Norway
4Department of Gynecology and Obstetrics, Stavanger University Hospital, P.O. Box 8100, 4068 Stavanger, Norway
5Department of Medical Biochemistry, Stavanger University Hospital, P.O. Box 8100, 4068 Stavanger, Norway
6Mediteam AS, Sjøveien 34, 4315 Sandnes, Norway
7The Gade Institute, University of Bergen, P.O. Box 1400, 5021 Bergen, Norway

Received 30 January 2014; Revised 29 April 2014; Accepted 14 May 2014; Published 15 June 2014

Academic Editor: Jen-Fu Chiu

Copyright © 2014 Kai-Erik Uleberg et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.