Abstract
Simple SummaryThe heterogeneity of epithelial ovarian cancer and its associated molecular biological characteristics are continuously integrated in the development of therapy guidelines. In a next step, future therapy recommendations might also be able to focus on the patient’s systemic status, not only the tumor’s molecular pattern. Therefore, new methods to identify and validate host-related biomarkers need to be established. Using mass spectrometry, we developed and independently validated a blood-based proteomic classifier, stratifying epithelial ovarian cancer patients into good and poor survival groups. We also determined an age dependence of the prognostic performance of this classifier and its association with important biological processes. This work highlights that, just like molecular markers of the tumor itself, the systemic condition of a patient (partly reflected in proteomic patterns) also influences survival and therapy response and could therefore be integrated into future processes of therapy planning.Mass-spectrometry-based analyses have identified a variety of candidate protein biomarkers that might be crucial for epithelial ovarian cancer (EOC) development and therapy response. Comprehensive validation studies of the biological and clinical implications of proteomics are needed to advance them toward clinical use. Using the Deep MALDI method of mass spectrometry, we developed and independently validated (development cohort: n = 199, validation cohort: n = 135) a blood-based proteomic classifier, stratifying EOC patients into good and poor survival groups. We also determined an age dependency of the prognostic performance of this classifier, and our protein set enrichment analysis showed that the good and poor proteomic phenotypes were associated with, respectively, lower and higher levels of complement activation, inflammatory response, and acute phase reactants. This work highlights that, just like molecular markers of the tumor itself, the systemic condition of a patient (partly reflected in proteomic patterns) also influences survival and therapy response in a subset of ovarian cancer patients and could therefore be integrated into future processes of therapy planning.
Highlights
Despite all the advances in ovarian cancer research, and the understanding of the heterogeneity of this disease, epithelial ovarian cancer (EOC) still has the highest mortality rate of all gynecological malignancies, with a five-year survival in advanced stages of only 30%
The development cohort (DC) comprised 199 patients with EOC treated at the Department of Gynecology and Obstetrics at University of Essen, Germany, diagnosed between
The independent validation cohort (VC) comprised 135 patients with EOC treated within the European OVCAD consortium (Berlin, Hamburg (Germany), Leuven
Summary
Despite all the advances in ovarian cancer research, and the understanding of the heterogeneity of this disease, epithelial ovarian cancer (EOC) still has the highest mortality rate of all gynecological malignancies, with a five-year survival in advanced stages of only 30%. Primary therapy for patients with EOC is radical cytoreductive surgery, followed by adjuvant platinum-based chemotherapy, administered in six cycles of carboplatin and paclitaxel with/without bevacizumab [1]. PARP (Poly(ADP-ribose)-Polymerase)-inhibition was introduced in the first-line-treatment for selected patients [2]. Initial response to therapy can be divided into three categories: platinum-resistant or -refractory, platinum-partially sensitive, and platinum-responsive. The duration of response to primary chemotherapy is considered the most important factor for treatment of recurrence [3]. Management of EOC could be improved by the use of validated biomarkers to identify patients, in advance of therapy, that are likely to be platinum resistant and at high risk of early progression [4]
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