Abstract

BackgroundDue to high mortality and lack of efficient screening, new tools for ovarian cancer (OC) diagnosis are urgently needed. To broaden the knowledge on the pathological processes that occur during ovarian cancer tumorigenesis, protein-peptide profiling was proposed.MethodsSerum proteomic patterns in samples from OC patients were obtained using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF). Eighty nine serum samples (44 ovarian cancer and 45 healthy controls) were pretreated using solid-phase extraction method. Next, a classification model with the most discriminative factors was identified using chemometric algorithms. Finally, the results were verified by external validation on an independent test set of samples.ResultsMain outcome of this study was an identification of potential OC biomarkers by applying liquid chromatography coupled with tandem mass spectrometry. Application of this novel strategy enabled the identification of four potential OC serum biomarkers (complement C3, kininogen-1, inter-alpha-trypsin inhibitor heavy chain H4, and transthyretin). The role of these proteins was discussed in relation to OC pathomechanism.ConclusionsThe study results may contribute to the development of clinically useful multi-component diagnostic tools in OC. In addition, identifying a novel panel of discriminative proteins could provide a new insight into complex signaling and functional networks associated with this multifactorial disease.

Highlights

  • Due to high mortality and lack of efficient screening, new tools for ovarian cancer (OC) diagnosis are urgently needed

  • Discriminatory power of the obtained peaks was further analyzed by calculating the receiver operating characteristic (ROC) curve, which represents a graphical relation between sensitivity and specificity (Fig. 1)

  • The applied methodology constitutes an objective tool for identification of the OC indicators, which may contribute to understanding the pathological processes and may facilitate the development of both novel diagnostic tools and molecular targeted therapies

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Summary

Introduction

Due to high mortality and lack of efficient screening, new tools for ovarian cancer (OC) diagnosis are urgently needed. Serum measurement of cancer antigen 125 (CA125) and transvaginal ultrasound examination have become the most widely used methods in OC diagnosis [4]. They are characterized by low specificity, especially in early stage cancer and in women before menopause [5]. Food and Drug Administration (FDA) cleared for use two multiple biomarker tests: Risk of Ovarian Malignancy Algorithm (ROMA) and OVA1 - a multivariate index assay (MIA). ROMA combines serum CA125 and HE4 levels with menopausal status

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