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

Zardiashvili M.D., Frankevich V.E., Nazarova N.M., Bugrova A.E., Kononikhin A.S., Brhozovsky А.G., Starodubtseva N.L., Asaturova A.V., Sukhikh G.T.

1Research Center of Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, Moscow, Russia 2 Moscow Institute of Physics and Technology, Dolgoprudny, Moscow Region, Russia 3Institute of Biomedical Problems – Russian Federation State Scientific Research Center, Russian Academy of Sciences, Moscow, Russia 4N.M. Emanuel Institute for Biochemical Physics, Russian Academy of Sciences, Moscow, Russia
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.

Keywords

cervical intraepithelial neoplasia
HPV
proteomics
mass spectrometry
cervicovaginal fluid

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Received 07.02.2017

Accepted 17.02.2017

About the Authors

Zardiashvili Maka Djemalovna, PhD student, Research Center of Obstetrics, Gynecology and Perinatology, Ministry Of Health of Russia.
117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +79163375351. E-mail: z-m-d@mail.ru
Frankevich Vladimir Evgenievich, PhD, Head of Department of Systems Biology in Reproduction, Research Center of Obstetrics, Gynecology and Perinatology,
Ministry Of Health of Russia. 117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +74954380788, ext. 2198. E-mail: v_frankevich@oparina4.ru
Nazarova Niso Mirzoevna, MD, PhD, Senior Researcher, Research Center of Obstetrics, Gynecology and Perinatology, Ministry Of Health of Russia.
117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +74954381403. E-mail: grab2@yandex.ru
Bugrova Anna Evgenievna, PhD, Senior Researcher of Proteomics of Human Reproduction, Research Center of Obstetrics, Gynecology and Perinatology,
Ministry Of Health of Russia. 117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +79265626590. E-mail: a_bugrova@oparina4.ru
Kononikhin Aleksey Sergeevich, PhD, Researcher of Proteomics of Human Reproduction, Research Center of Obstetrics, Gynecology and Perinatology,
Ministry Of Health of Russia. 117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +79167854781. E-mail: konoleha@yandex.ru
Brhozovsky Alexander Gennadievich, PhD student of Laboratory of proteomics, Institute of Biomedical Problems – Russian Federation State Scientific Research Center, Russian Academy of Sciences. 123007, Russia, Moscow, Khoroshevskoye shosse 76. Tel.: +79167705168. E-mail: agb.imbp@gmail.com
Starodubtseva Nataliia Leonidovna, PhD, Head of Laboratory of Proteomics of Human Reproduction, Research Center of Obstetrics, Gynecology and Perinatology,
Ministry Of Health of Russia. 117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +79164639867. E-mail: n_starodubtseva@oparina4.ru
Asaturova Aleksandra Vyacheslavovna, PhD, Senior Researcher of pathologoanatomic department, Research Center of Obstetrics, Gynecology and Perinatology,
Ministry Of Health of Russia. 117997, Russia, Moscow, Ac. Oparina str. 4. Tel. +74954382311. E-mail: a_asaturova@oparina4.ru
Sukhikh Gennadiy Tikhonovich, Academician of RAMS, MD, PhD, Professor, Director, Research Center of Obstetrics, Gynecology and Perinatology,
Ministry Of Health of Russia. 117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +74954381800. E-mail: g_sukhikh@oparina4.ru

For citations: Zardiashvili M.D., Frankevich V.E., Nazarova N.M., Bugrova A.E., Kononikhin A.S., Brhozovsky А.G., Starodubtseva N.L., Asaturova A.V., Sukhikh G.T. Proteomic composition of cervicovaginal fluid in cervical diseases associated with HPV infection. Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2017; (4): 88-94. (in Russian)
http://dx.doi.org/10.18565/aig.2017.4.88-94

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