Platelet protein biomarker panel for ovarian cancer diagnosis

Marta Lomnytska; Rui Pinto; Susanne Becker; Ulla Engström; Sonja Gustafsson; Christina Björklund; Markus Templin; Jan Bergstrand; Lei Xu; Jerker Widengren; Elisabeth Epstein; Bo Franzén; Gert Auer

doi:10.1186/s40364-018-0118-y

Platelet protein biomarker panel for ovarian cancer diagnosis

Biomark Res. 2018 Jan 12:6:2. doi: 10.1186/s40364-018-0118-y. eCollection 2018.

Authors

Marta Lomnytska^{1

2

3}, Rui Pinto⁴, Susanne Becker³, Ulla Engström⁵, Sonja Gustafsson⁶, Christina Björklund⁶, Markus Templin⁷, Jan Bergstrand⁸, Lei Xu⁸, Jerker Widengren⁸, Elisabeth Epstein^{2

9}, Bo Franzén^{3

6}, Gert Auer^{3

6}

Affiliations

¹ 1Department of Obstetrics and Gynaecology, Academical Uppsala University Hospital, Uppsala University, SE-751 85 Uppsala, Sweden.
² 2Institute of Women's and Children's Health, Karolinska Institute, SE-171 76 Stockholm, Sweden.
³ 3Department of Oncology and Pathology, Cancer Centre Karolinska, Karolinska Institute, SE-171 76 Stockholm, Sweden.
⁴ 4Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, St. Mary's Campus, Norfolk Place, W2 1PG, London, England UK.
⁵ 5Ludwig Institute for Cancer Research Ltd, Box 595, SE-751 24 Uppsala, Sweden.
⁶ NeoProteomics AB, Cancer Centre Karolinska, SE-17176 Stockholm, Sweden.
⁷ 7NMI Natural and Medical Sciences Institute at the University of Tübingen, 72770 Reutlingen, Germany.
⁸ 8Experimental Biomolecular Physics, Department of Applied Physics, Royal Institute of Technology, AlbaNova University Center, SE-106 91 Stockholm, Sweden.
⁹ Department of Obstetrics and Gynaecology, Department of Clinical Science and Education, Södersjukhuset, SE-118 83 Stockholm, Sweden.

Abstract

Background: Platelets support cancer growth and spread making platelet proteins candidates in the search for biomarkers.

Methods: Two-dimensional (2D) gel electrophoresis, Partial Least Squares Discriminant Analysis (PLS-DA), Western blot, DigiWest.

Results: PLS-DA of platelet protein expression in 2D gels suggested differences between the International Federation of Gynaecology and Obstetrics (FIGO) stages III-IV of ovarian cancer, compared to benign adnexal lesions with a sensitivity of 96% and a specificity of 88%. A PLS-DA-based model correctly predicted 7 out of 8 cases of FIGO stages I-II of ovarian cancer after verification by western blot. Receiver-operator curve (ROC) analysis indicated a sensitivity of 83% and specificity of 76% at cut-off >0.5 (area under the curve (AUC) = 0.831, p < 0.0001) for detecting these cases. Validation on an independent set of samples by DigiWest with PLS-DA differentiated benign adnexal lesions and ovarian cancer, FIGO stages III-IV, with a sensitivity of 70% and a specificity of 83%.

Conclusion: We identified a group of platelet protein biomarker candidates that can quantify the differential expression between ovarian cancer cases as compared to benign adnexal lesions.

Keywords: Biomarker; Liquid biopsy; Ovarian cancer; Platelet proteome.