Identification of protein biomarkers for cervical cancer using human cervicovaginal fluid
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...
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| Veröffentlicht in: | PloS one 2014-09, Vol.9 (9), p.e106488-e106488 |
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| creator | Van Raemdonck, Geert A A Tjalma, Wiebren A A Coen, Edmond P Depuydt, Christophe E Van Ostade, Xaveer W M |
| description | 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.
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.
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.
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. |
| doi_str_mv | 10.1371/journal.pone.0106488 |
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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.
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.
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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0106488</identifier><identifier>PMID: 25215525</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Actinin ; Actinin - metabolism ; Aged ; Bioindicators ; Biology and Life Sciences ; Biomarkers ; Biomarkers, Tumor - metabolism ; Body Fluids - metabolism ; Cancer ; Cell cycle ; Cell division ; Cellular biology ; Cervical cancer ; Cervix ; Cervix Uteri - metabolism ; Clearing ; Enzyme-Linked Immunosorbent Assay ; Epigenetics ; Female ; Fluids ; Gene amplification ; Genital tract ; Health risks ; Human papillomavirus ; Humans ; Immunization ; Kinases ; Laboratories ; Longitudinal Studies ; Mass spectrometry ; Medical screening ; Medicine and Health Sciences ; Metabolism ; Middle Aged ; Neoplasm Proteins - metabolism ; Ovarian cancer ; Papillomaviridae - physiology ; Plasma ; Precancerous Conditions - metabolism ; Protein sources ; Proteins ; Proteomics ; Pyruvate kinase ; Pyruvic acid ; Reproducibility of Results ; Reproductive system ; Scientific imaging ; Self tests ; Studies ; Trends ; Uterine Cervical Neoplasms - metabolism ; Uterine Cervical Neoplasms - virology ; Vaccines ; Vagina - metabolism ; Viruses ; Womens health</subject><ispartof>PloS one, 2014-09, Vol.9 (9), p.e106488-e106488</ispartof><rights>2014 Van Raemdonck et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2014 Van Raemdonck et al 2014 Van Raemdonck et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c526t-289599d222dcb8bc2ec7e707061b0ce457ec71aee57ea06c5b0c09ff8c0daf973</citedby><cites>FETCH-LOGICAL-c526t-289599d222dcb8bc2ec7e707061b0ce457ec71aee57ea06c5b0c09ff8c0daf973</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4162552/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4162552/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,724,777,781,861,882,2096,2915,23847,27905,27906,53772,53774,79349,79350</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25215525$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Veedu, Rakesh N.</contributor><creatorcontrib>Van Raemdonck, Geert A A</creatorcontrib><creatorcontrib>Tjalma, Wiebren A A</creatorcontrib><creatorcontrib>Coen, Edmond P</creatorcontrib><creatorcontrib>Depuydt, Christophe E</creatorcontrib><creatorcontrib>Van Ostade, Xaveer W M</creatorcontrib><title>Identification of protein biomarkers for cervical cancer using human cervicovaginal fluid</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>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.
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.
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.
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.</description><subject>Actinin</subject><subject>Actinin - metabolism</subject><subject>Aged</subject><subject>Bioindicators</subject><subject>Biology and Life Sciences</subject><subject>Biomarkers</subject><subject>Biomarkers, Tumor - metabolism</subject><subject>Body Fluids - metabolism</subject><subject>Cancer</subject><subject>Cell cycle</subject><subject>Cell division</subject><subject>Cellular biology</subject><subject>Cervical cancer</subject><subject>Cervix</subject><subject>Cervix Uteri - metabolism</subject><subject>Clearing</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Epigenetics</subject><subject>Female</subject><subject>Fluids</subject><subject>Gene amplification</subject><subject>Genital tract</subject><subject>Health risks</subject><subject>Human papillomavirus</subject><subject>Humans</subject><subject>Immunization</subject><subject>Kinases</subject><subject>Laboratories</subject><subject>Longitudinal Studies</subject><subject>Mass spectrometry</subject><subject>Medical screening</subject><subject>Medicine and Health Sciences</subject><subject>Metabolism</subject><subject>Middle Aged</subject><subject>Neoplasm Proteins - 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metabolism</topic><topic>Aged</topic><topic>Bioindicators</topic><topic>Biology and Life Sciences</topic><topic>Biomarkers</topic><topic>Biomarkers, Tumor - metabolism</topic><topic>Body Fluids - metabolism</topic><topic>Cancer</topic><topic>Cell cycle</topic><topic>Cell division</topic><topic>Cellular biology</topic><topic>Cervical cancer</topic><topic>Cervix</topic><topic>Cervix Uteri - metabolism</topic><topic>Clearing</topic><topic>Enzyme-Linked Immunosorbent Assay</topic><topic>Epigenetics</topic><topic>Female</topic><topic>Fluids</topic><topic>Gene amplification</topic><topic>Genital tract</topic><topic>Health risks</topic><topic>Human papillomavirus</topic><topic>Humans</topic><topic>Immunization</topic><topic>Kinases</topic><topic>Laboratories</topic><topic>Longitudinal Studies</topic><topic>Mass spectrometry</topic><topic>Medical screening</topic><topic>Medicine and Health Sciences</topic><topic>Metabolism</topic><topic>Middle Aged</topic><topic>Neoplasm Proteins - metabolism</topic><topic>Ovarian cancer</topic><topic>Papillomaviridae - physiology</topic><topic>Plasma</topic><topic>Precancerous Conditions - metabolism</topic><topic>Protein sources</topic><topic>Proteins</topic><topic>Proteomics</topic><topic>Pyruvate kinase</topic><topic>Pyruvic acid</topic><topic>Reproducibility of Results</topic><topic>Reproductive system</topic><topic>Scientific imaging</topic><topic>Self tests</topic><topic>Studies</topic><topic>Trends</topic><topic>Uterine Cervical Neoplasms - metabolism</topic><topic>Uterine Cervical Neoplasms - virology</topic><topic>Vaccines</topic><topic>Vagina - metabolism</topic><topic>Viruses</topic><topic>Womens health</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Van Raemdonck, Geert A A</creatorcontrib><creatorcontrib>Tjalma, Wiebren A A</creatorcontrib><creatorcontrib>Coen, Edmond P</creatorcontrib><creatorcontrib>Depuydt, Christophe E</creatorcontrib><creatorcontrib>Van Ostade, Xaveer W M</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Van Raemdonck, Geert A A</au><au>Tjalma, Wiebren A A</au><au>Coen, Edmond P</au><au>Depuydt, Christophe E</au><au>Van Ostade, Xaveer W M</au><au>Veedu, Rakesh N.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Identification of protein biomarkers for cervical cancer using human cervicovaginal fluid</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2014-09-12</date><risdate>2014</risdate><volume>9</volume><issue>9</issue><spage>e106488</spage><epage>e106488</epage><pages>e106488-e106488</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>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.
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.
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.
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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25215525</pmid><doi>10.1371/journal.pone.0106488</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Actinin Actinin - metabolism Aged Bioindicators Biology and Life Sciences Biomarkers Biomarkers, Tumor - metabolism Body Fluids - metabolism Cancer Cell cycle Cell division Cellular biology Cervical cancer Cervix Cervix Uteri - metabolism Clearing Enzyme-Linked Immunosorbent Assay Epigenetics Female Fluids Gene amplification Genital tract Health risks Human papillomavirus Humans Immunization Kinases Laboratories Longitudinal Studies Mass spectrometry Medical screening Medicine and Health Sciences Metabolism Middle Aged Neoplasm Proteins - metabolism Ovarian cancer Papillomaviridae - physiology Plasma Precancerous Conditions - metabolism Protein sources Proteins Proteomics Pyruvate kinase Pyruvic acid Reproducibility of Results Reproductive system Scientific imaging Self tests Studies Trends Uterine Cervical Neoplasms - metabolism Uterine Cervical Neoplasms - virology Vaccines Vagina - metabolism Viruses Womens health |
| title | Identification of protein biomarkers for cervical cancer using human cervicovaginal fluid |
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