title: Identification of protein biomarkers for cervical cancer using human cervicovaginal fluid.
abstract: OBJECTIVE
  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.
authors.affiliation: Laboratory for Protein Science, Proteomics and Epigenetic Signaling (PPES) and Centre for Proteomics and Mass spectrometry (CeProMa), University of Antwerp, Wilrijk, Belgium.
authors.forename: Geert A A
authors.initials: GA
authors.lastname: Van Raemdonck
authors.affiliation: Department of Gynaecology and Gynaecologic Oncology, University Hospital Antwerp, Edegem, Belgium.
authors.forename: Wiebren A A
authors.initials: WA
authors.lastname: Tjalma
authors.affiliation: Laboratory for Protein Science, Proteomics and Epigenetic Signaling (PPES) and Centre for Proteomics and Mass spectrometry (CeProMa), University of Antwerp, Wilrijk, Belgium.
authors.forename: Edmond P
authors.initials: EP
authors.lastname: Coen
authors.affiliation: Department of Molecular Diagnostics, Algemeen Medisch Laboratorium bvba, Sonic Healthcare Benelux, Antwerpen, Belgium.
authors.forename: Christophe E
authors.initials: CE
authors.lastname: Depuydt
authors.affiliation: Laboratory for Protein Science, Proteomics and Epigenetic Signaling (PPES) and Centre for Proteomics and Mass spectrometry (CeProMa), University of Antwerp, Wilrijk, Belgium.
authors.forename: Xaveer W M
authors.initials: XW
authors.lastname: Van Ostade
mesh_terms: D000185:Actinin / Q000378:metabolism; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001826:Body Fluids / Q000378:metabolism*; D002584:Cervix Uteri / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D027383:Papillomaviridae / Q000502:physiology; D011230:Precancerous Conditions / Q000378:metabolism; D040901:Proteomics; D015203:Reproducibility of Results; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000821:virology; D014621:Vagina / Q000378:metabolism*
chemical_list: C111453:ACTN4 protein, human; D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D000185:Actinin