Proteomic composition of cervicovaginal fluid in cervical diseases associated with HPV infection


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Abstract

Objective. To determine changes of the cervicovaginal fluid proteomic composition for assessment of the severity of HPV-associated cervical lesions among women of reproductive age. Subject and methods. The study involved 30 volunteers with various forms of HPV-associated cervical lesions (ASCUS, LSIL and HSIL). All samples of cervicovaginal fluid were prepared for further proteomic analysis by tandem mass spectrometry (HPLC-MS/MS). Semi-quantitative data analysis including identification and annotation of proteins was carried out using the software package MaxQuant and Perseus. Results. The protein panels specific to the various forms of HPV-associated cervical lesions (ASCUS, LSIL and HSIL) were identified. The first group of proteins (P4HB, HSPA8, C4BPA and others) characterized the early changes associated with HPV infection and cervical epithelium lesion, including viruspenetration into the cell and its transcription, impaired function of the complement system. The second group of proteins (PRDX5, YWHAE, LRG1 and others) were directly involved in the development and progression of cervical neoplasia and characterized late changes, in particular, reduced apoptosis, impaired differentiation and maturation of the epithelium, and the transformation of atypical cells. Conclusion. The analysis of the proteome of the CVH allows to study the molecular mechanisms of the pathogenesis of HPV-associated cervical diseases and to differentiate epithelial changes at early stages of development.

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About the authors

Maka Djemalovna Zardiashvili

Research Center of Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: z-m-d@mail.ru
PhD student

Vladimir Evgenievich Frankevich

Research Center of Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: v_frankevich@oparina4.ru
PhD, Head of Department of Systems Biology in Reproduction

Niso Mirzoevna Nazarova

Research Center of Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: grab2@yandex.ru
MD, PhD, Senior Researcher

Anna Evgenievna Bugrova

Research Center of Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia; N.M. Emanuel Institute for Biochemical Physics, Russian Academy of Sciences

Email: a_bugrova@oparina4.ru
PhD, Senior Researcher of Proteomics of Human Reproduction

Aleksey Sergeevich Kononikhin

Research Center of Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: konoleha@yandex.ru
PhD, Researcher of Proteomics of Human Reproduction

Alexander Gennadievich Brhozovsky

Institute of Biomedical Problems - Russian Federation State Scientific Research Center, Russian Academy of Sciences

Email: agb.imbp@gmail.com
PhD student of Laboratory of proteomics

Nataliia Leonidovna Starodubtseva

Research Center of Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia; Moscow Institute of Physics and Technology

Email: n_starodubtseva@oparina4.ru
PhD, Head of Laboratory of Proteomics of Human Reproduction

Aleksandra Vyacheslavovna Asaturova

Research Center of Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: g_sukhikh@oparina4.ru
PhD, Senior Researcher of pathologoanatomic department

Gennadiy Tikhonovich Sukhikh

Research Center of Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Academician of RAS, MD, PhD, Professor, Director

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