Characteristics of dynamic changes in proteomic composition of cervicovaginal fluid in cervical diseases associated with HPV infection


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Abstract

Objective. To develop a non-invasive approach to the differential diagnosis of HPV-associated cervical diseases in patients of reproductive age with minor lesions of the cervical epithelium based on a proteomic analysis of cervicovaginal fluid (CVF). Materials and methods. Samples of CVF were obtained from seven patients aged 26-36 years (31 ± 4) with minor HPV-associated cervical lesions (ASCUS, LSIL) during the dynamic observation (0, 6 and 12 months). Semi-quantitative analysis of proteomic data (HPLC-MS/MS), including protein identification and annotation, was carried out using the MaxQuant and STRING software. Results. A significant change in the level of seven proteins SOD1, CSTA, FGB, ENO1, BPI, BPIFB1, SERPINB13 was revealed during the dynamic observation. The analysis of enriching functional groups based on GeneOntology data showed that these proteins are most associated with the activation of immune (innate immunity) and antimicrobial processes, and are also involved in the regulation of apoptosis and epithelial-mesenchymal transformation. The change in the level of the proteins is likely to be mediated by the elimination of the HPV virus and associated neoplastic transformation of the cervical epithelium. Conclusion. Proteomic analysis of CVF revealed a panel of proteins that can be used to assess the dynamics of the pathological process and the effectiveness of the chosen treatment strategy for patients with neoplastic changes in the cervix.

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About the authors

Natalia L. Starodubtseva

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: n_starodubtseva@oparina4.ru
Ph.D., Head of the Laboratory of Proteomics of Human Reproduction

Alexander G. Brzhozovskiy

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia; Skolkovo Institute of Science and Technology

Email: agb.imbp@gmail.com
Researcher, Laboratory of Proteomics of Human Reproduction

Anna E. Bugrova

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia; N.M. Emanuel Institute of Biochemical Physics of RAS

Email: a_bugrova@oparina4.ru
Ph.D., Senior Researcher, Laboratory of Proteomics of Human Reproduction

Aleksey S. Kononikhin

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia; Skolkovo Institute of Science and Technology

Email: konoleha@yandex.ru
Ph.D. Researcher, Laboratory of Proteomics of Human Reproduction

Kirill I. Gusakov

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: kigusakov@gmail.com
PhD Student

Niso M. Nazarova

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: grab2@yandex.ru
MD, Leading Researcher

Vladimir E. Frankevich

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: v_frankevich@oparina4.ru
Ph.D., Head of the Department of system biology in reproduction

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