Identification of protein biomarkers for cervical cancer using human cervicovaginal fluid

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Authors
Raemdonck, Geert A. A. Van
Tjalma, Wiebren A. A.
Coen, Edmond P.
Depuydt, Christophe E.
Ostade, Xaveer W. M. Van
Issue Date
2014-09-12
Type
Article
Language
en_US
Keywords
Protein Biomarkers , Cervical Cancer , Human Cervicovaginal Fluid
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Abstract
Objectives: Cervicovaginal 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. Methods: A differential proteomics study was set up using CVF samples from healthy and precancerous women. Label-free spectral counting was applied to quantify protein abundances. Results: The 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. Conclusions: Our 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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Van Raemdonck, G. A., Tjalma, W. A., Coen, E. P., Depuydt, C. E., & Van Ostade, X. W. (2014). Identification of protein biomarkers for cervical cancer using human cervicovaginal fluid. PloS one, 9(9), e106488. https://doi.org/10.1371/journal.pone.0106488
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PloS One
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