Identification of Protein Biomarkers for Cervical Cancer Using Human Cervicovaginal Fluid |
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Authors: | Geert A A Van Raemdonck Wiebren A A Tjalma Edmond P Coen Christophe E Depuydt Xaveer W M Van Ostade |
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Institution: | 1. Laboratory for Protein Science, Proteomics and Epigenetic Signaling (PPES) and Centre for Proteomics and Mass spectrometry (CeProMa), University of Antwerp, Wilrijk, Belgium.; 2. Department of Gynaecology and Gynaecologic Oncology, University Hospital Antwerp, Edegem, Belgium.; 3. Department of Molecular Diagnostics, Algemeen Medisch Laboratorium bvba, Sonic Healthcare Benelux, Antwerpen, Belgium.; The University of Queensland, Australia, |
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Abstract: | ObjectivesCervicovaginal fluid (CVF) can be considered as a potential source of biomarkers for diseases of the lower female reproductive tract. The fluid can easily be collected, thereby offering new opportunities such as the development of self tests. Our objective was to identify a CVF protein biomarker for cervical cancer or its precancerous state.MethodsA differential proteomics study was set up using CVF samples from healthy and precancerous women. Label-free spectral counting was applied to quantify protein abundances.ResultsThe proteome analysis revealed 16 candidate biomarkers of which alpha-actinin-4 (p = 0.001) and pyruvate kinase isozyme M1/M2 (p = 0.014) were most promising. Verification of alpha-actinin-4 by ELISA (n = 28) showed that this candidate biomarker discriminated between samples from healthy and both low-risk and high-risk HPV-infected women (p = 0.009). Additional analysis of longitudinal samples (n = 29) showed that alpha-actinin-4 levels correlated with virus persistence and clearing, with a discrimination of approximately 18 pg/ml.ConclusionsOur results show that CVF is an excellent source of protein biomarkers for detection of lower female genital tract pathologies and that alpha-actinin-4 derived from CVF is a promising candidate biomarker for the precancerous state of cervical cancer. Further studies regarding sensitivity and specificity of this biomarker will demonstrate its utility for improving current screening programs and/or its use for a cervical cancer self-diagnosis test. |
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