IPA Analysis of Cervicovaginal Fluid from Precancerous Women Points to the Presence of Biomarkers for the Precancerous State of Cervical Carcinoma

Despite large gaps in our knowledge on the intracellular mechanism leading to cervical cancer, the pathways induced by oncogenic high-risk Human Papilloma Virus (HPV) and those finally causing cervical cancer are increasingly being unraveled. Assuming that precancerous tissue is recognized and lysed...

Full description

Bibliographic Details
Main Authors: Xaveer Van Ostade, Martin Dom, Geert Van Raemdonck
Format: Article
Language:English
Published: MDPI AG 2014-08-01
Series:Proteomes
Subjects:
Online Access:http://www.mdpi.com/2227-7382/2/3/426
_version_ 1818006964280492032
author Xaveer Van Ostade
Martin Dom
Geert Van Raemdonck
author_facet Xaveer Van Ostade
Martin Dom
Geert Van Raemdonck
author_sort Xaveer Van Ostade
collection DOAJ
description Despite large gaps in our knowledge on the intracellular mechanism leading to cervical cancer, the pathways induced by oncogenic high-risk Human Papilloma Virus (HPV) and those finally causing cervical cancer are increasingly being unraveled. Assuming that precancerous tissue is recognized and lysed by the immune system—which is in many cases incomplete because of the counteraction by the HPV virus—we hypothesize that several intracellular factors, involved in induction and development of precancerous lesions and/or cervical cancer are being released into the cervicovaginal fluid (CVF). These factors can then be seen as markers for the precancerous state, and when they persist they are indicative for an increased risk for cervical carcinoma. In a previous study, we analyzed the proteomic profiles of six CVF samples from women with different stages of precancerous lesions and compared these with the CVF proteomes from healthy women. Here, we extend these observations by investigating these proteomes by Ingenuity Pathway Analysis (IPA). We show that proteins in CVF from precancerous women are clearly more involved in pathways that make up the ‘hallmarks of cancer’, as compared to CVF proteins from healthy persons. Moreover, after literature search, proteins classified by IPA in the ‘cancer’ category, were more correlated with cervical cancer when they originated from CVF from precancerous women. Many of these proteins formed a network with angiotensin II as central mediator. The search for ‘network biomarkers’, rather than single biomarkers, could drastically increase specificity, sensitivity and prognostic value of cervical cancer diagnosis, making use of an easy to handle fluid, the CVF.
first_indexed 2024-04-14T05:08:35Z
format Article
id doaj.art-9b99b9218e394ccaa246da5b99da4a09
institution Directory Open Access Journal
issn 2227-7382
language English
last_indexed 2024-04-14T05:08:35Z
publishDate 2014-08-01
publisher MDPI AG
record_format Article
series Proteomes
spelling doaj.art-9b99b9218e394ccaa246da5b99da4a092022-12-22T02:10:37ZengMDPI AGProteomes2227-73822014-08-012342645010.3390/proteomes2030426proteomes2030426IPA Analysis of Cervicovaginal Fluid from Precancerous Women Points to the Presence of Biomarkers for the Precancerous State of Cervical CarcinomaXaveer Van Ostade0Martin Dom1Geert Van Raemdonck2Laboratory for Protein Science, Proteomics and Epigenetic Signaling (PPES), University of Antwerp, Universiteitsplein 1, Wilrijk 2610, BelgiumLaboratory for Protein Science, Proteomics and Epigenetic Signaling (PPES), University of Antwerp, Universiteitsplein 1, Wilrijk 2610, BelgiumLaboratory for Protein Science, Proteomics and Epigenetic Signaling (PPES), University of Antwerp, Universiteitsplein 1, Wilrijk 2610, BelgiumDespite large gaps in our knowledge on the intracellular mechanism leading to cervical cancer, the pathways induced by oncogenic high-risk Human Papilloma Virus (HPV) and those finally causing cervical cancer are increasingly being unraveled. Assuming that precancerous tissue is recognized and lysed by the immune system—which is in many cases incomplete because of the counteraction by the HPV virus—we hypothesize that several intracellular factors, involved in induction and development of precancerous lesions and/or cervical cancer are being released into the cervicovaginal fluid (CVF). These factors can then be seen as markers for the precancerous state, and when they persist they are indicative for an increased risk for cervical carcinoma. In a previous study, we analyzed the proteomic profiles of six CVF samples from women with different stages of precancerous lesions and compared these with the CVF proteomes from healthy women. Here, we extend these observations by investigating these proteomes by Ingenuity Pathway Analysis (IPA). We show that proteins in CVF from precancerous women are clearly more involved in pathways that make up the ‘hallmarks of cancer’, as compared to CVF proteins from healthy persons. Moreover, after literature search, proteins classified by IPA in the ‘cancer’ category, were more correlated with cervical cancer when they originated from CVF from precancerous women. Many of these proteins formed a network with angiotensin II as central mediator. The search for ‘network biomarkers’, rather than single biomarkers, could drastically increase specificity, sensitivity and prognostic value of cervical cancer diagnosis, making use of an easy to handle fluid, the CVF.http://www.mdpi.com/2227-7382/2/3/426cervicovaginal fluidbiomarkercervical cancer
spellingShingle Xaveer Van Ostade
Martin Dom
Geert Van Raemdonck
IPA Analysis of Cervicovaginal Fluid from Precancerous Women Points to the Presence of Biomarkers for the Precancerous State of Cervical Carcinoma
Proteomes
cervicovaginal fluid
biomarker
cervical cancer
title IPA Analysis of Cervicovaginal Fluid from Precancerous Women Points to the Presence of Biomarkers for the Precancerous State of Cervical Carcinoma
title_full IPA Analysis of Cervicovaginal Fluid from Precancerous Women Points to the Presence of Biomarkers for the Precancerous State of Cervical Carcinoma
title_fullStr IPA Analysis of Cervicovaginal Fluid from Precancerous Women Points to the Presence of Biomarkers for the Precancerous State of Cervical Carcinoma
title_full_unstemmed IPA Analysis of Cervicovaginal Fluid from Precancerous Women Points to the Presence of Biomarkers for the Precancerous State of Cervical Carcinoma
title_short IPA Analysis of Cervicovaginal Fluid from Precancerous Women Points to the Presence of Biomarkers for the Precancerous State of Cervical Carcinoma
title_sort ipa analysis of cervicovaginal fluid from precancerous women points to the presence of biomarkers for the precancerous state of cervical carcinoma
topic cervicovaginal fluid
biomarker
cervical cancer
url http://www.mdpi.com/2227-7382/2/3/426
work_keys_str_mv AT xaveervanostade ipaanalysisofcervicovaginalfluidfromprecancerouswomenpointstothepresenceofbiomarkersfortheprecancerousstateofcervicalcarcinoma
AT martindom ipaanalysisofcervicovaginalfluidfromprecancerouswomenpointstothepresenceofbiomarkersfortheprecancerousstateofcervicalcarcinoma
AT geertvanraemdonck ipaanalysisofcervicovaginalfluidfromprecancerouswomenpointstothepresenceofbiomarkersfortheprecancerousstateofcervicalcarcinoma