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Abstract
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.
Highlights
From the lists of unique cervicovaginal fluid (CVF) proteins we identified from healthy and precancerous women, pathway reconstruction was performed using the Ingenuity Pathway Analysis software
Proteins in the CVF proteome from precancerous individuals tended to be more involved in pathways that contribute in cancer processes, when compared to CVF proteins from healthy individuals
Examination of the literature from CVF proteins categorized by Ingenuity Pathway Analysis (IPA) as being involved in
Summary
Many secretions have a specific physiological function and act as physical and chemical barriers against pathogens that may come into contact with the soft, non-keratinized tissue separating the organ from the exterior. Consider organismal secretions as relatively easy obtainable fingerprints, handed to us by nature, as to inform us about the physiological state of the inside of our body and its state of defense against assaults from the outside. Examples of such secretions are feces, urine, brochoalveolar fluid, sweat, milk, tear fluid, saliva, semen, or cervicovaginal fluid
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