Discovery of Prognostic Markers for Early-Stage High-Grade Serous Ovarian Cancer by Maldi-Imaging

Hagen Kulbe; Oliver Klein; Zhiyang Wu; Eliane T Taube; Wanja Kassuhn; David Horst; Silvia Darb-Esfahani; Paul Jank; Salem Abobaker; Frauke Ringel; Andreas du Bois; Florian Heitz; Jalid Sehouli; Elena I Braicu

doi:10.3390/cancers12082000

Discovery of Prognostic Markers for Early-Stage High-Grade Serous Ovarian Cancer by Maldi-Imaging

Cancers (Basel). 2020 Jul 22;12(8):2000. doi: 10.3390/cancers12082000.

Authors

Hagen Kulbe^{1

2}, Oliver Klein³, Zhiyang Wu³, Eliane T Taube⁴, Wanja Kassuhn^{1

2}, David Horst⁴, Silvia Darb-Esfahani⁵, Paul Jank^{4

6}, Salem Abobaker^{1

2}, Frauke Ringel^{1

2}, Andreas du Bois⁷, Florian Heitz⁷, Jalid Sehouli^{1

2}, Elena I Braicu^{1

2}

Affiliations

¹ Tumorbank Ovarian Cancer Network, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany.
² Department of Gynecology, European Competence Center for Ovarian Cancer, Charité Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany.
³ BIH Center for Regenerative Therapies BCRT, Charité - Universitätsmedizin Berlin, 10117 Berlin, Germany.
⁴ Institute of Pathology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany.
⁵ Institute of Pathology Berlin-Spandau and Berlin-Buch, 10117 Berlin, Germany.
⁶ Institute of Pathology, Philipps-University Marburg, 35032 Marburg, Germany.
⁷ Evangelische Kliniken Essen-Mitte Klinik für Gynäkologie und gynäkologische Onkologie, 45136 Essen, Germany.

Abstract

With regard to relapse and survival, early-stage high-grade serous ovarian (HGSOC) patients comprise a heterogeneous group and there is no clear consensus on first-line treatment. Currently, no prognostic markers are available for risk assessment by standard targeted immunohistochemistry and novel approaches are urgently required. Here, we applied MALDI-imaging mass spectrometry (MALDI-IMS), a new method to identify distinct mass profiles including protein signatures on paraffin-embedded tissue sections. In search of prognostic biomarker candidates, we compared proteomic profiles of primary tumor sections from early-stage HGSOC patients with either recurrent (RD) or non-recurrent disease (N = 4; each group) as a proof of concept study. In total, MALDI-IMS analysis resulted in 7537 spectra from the malignant tumor areas. Using receiver operating characteristic (ROC) analysis, 151 peptides were able to discriminate between patients with RD and non-RD (AUC > 0.6 or < 0.4; p < 0.01), and 13 of them could be annotated to proteins. Strongest expression levels of specific peptides linked to Keratin type1 and Collagen alpha-2(I) were observed and associated with poor prognosis (AUC > 0.7). These results confirm that in using IMS, we could identify new candidates to predict clinical outcome and treatment extent for patients with early-stage HGSOC.

Keywords: MALDI-IMS; early-stage HGSOC; ovarian cancer; prognostic markers.