Lipid markers of cervical epithelium neoplastic transformation in HPV-associated diseases
Objective. To discover peculiarities of the lipid composition of neoplastically transformed and adjacent cervical epithelium with HPV-associated diseases.Nekrasova M.E., Chagovets V.V., Starodubtseva N.L., Kononikhin A.S., Salimova D.F., Tokareva A.O., Lagutin V.V., Naumov V.A., Nazarova N.M., Frankevich V.E., Sukhikh G.T.
Material and methods. The study included 41 patients with neoplastic transformations of the cervical epithelium, caused by human papillomavirus, who applied to outpatient department of Federal State Budget Institution “National Medical Research Center for Obstetrics, Gynecology and Perinatology” Ministry Of Healthcare of the Russian Federation. А biopsy of the cervix uteri (strictly according to the indications for biopsy) with subsequent histological examination of the biopsy specimens and analysis of their lipid composition were performed in all women, included in the study. Qualitative and quantitative assessment of biopsy samples lipid extracts was performed by mass spectrometry with electrospray ionization. Lipids of five classes were identified: phosphatidylcholines, phosphatidylethanolamines, sphingomyelins, di – and triglycerides. The obtained experimental data were analyzed using the multivariate OPLS-DA method.
Results. A statistically meaningful change in the levels of lipids, such as phosphatidylcholines (PC 32:0, PC 34:1, PC 36:4, PC 34:0, PC 38:4), phosphatidylethanolamines (PE O-46:0, LPE 46:0, PE O-48:0, LPE 48:0, PE O-46:1) and sphingomyelins (SM 34:0, SM 42:2 )was identified in cervical tissues with neoplastic transformation, caused by human papillomavirus.
Conclusion. This study revealed significant changes in the content of several glycerophospholipids and sphingolipids in neoplastically transformed tissues of the cervix uteri compared to adjacent normal tissues. Found lipids can be used as a part of the prognostic panel to predict the course of cervical neoplasias in the direction of regress or malignancy.
Keywords
cervical intraepithelial neoplasia
cervical cancer
human papillomavirus
biomarkers
microenvironment
mass spectrometry
lipids
phosphatidylcholine
sphingomyelin
Supplementary Materials
- Fig. 1. Score plots based on the OPLS-DA analysis of mass spectrometric data when comparing the lipid composition of pathological and borderline tissues from patients with a) chronic cervicitis (in combination with HPV infection); b) LSIL; c) HSIL; d) cervical cancer. Blue dots correspond to borderline tissues, red dots correspond to pathological
- Fig. 2. Score plots based on the OPLS-DA analysis of mass spectrometric data when comparing the lipid composition of tissues of patients with different diagnoses a) borderline tissues; b) pathological tissues. Color marking corresponds to the diagnosis, which was made according to the results of histological examination. Green dots correspond to chronic cervicitis (in combination with HPV infection), blue dots correspond to LSIL, yellow dots correspond to HSIL, red dots correspond to cervical cancer
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Received 08.12.2017
Accepted 22.12.2017
About the Authors
Nekrasova Maria Evgenievna, PhD student, National Medical Research Center of Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia namedafter Academician V.I. Kulakov. 117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +74954381403. E-mail: mashenka_90@mail.ru
Chagovets Vitaliy Viktorovich, PhD, Senior Researcher of Laboratory of Proteomics and Metabolomics of Human Reproduction, National Medical Research
Center of Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia named after Academician V.I. Kulakov.
117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +79169191466. E-mail: vvchagovets@gmail.com
Starodubtseva Nataliia Leonidovna, PhD, Head of Laboratory of Proteomics and Metabolomics of Human Reproduction, National Medical Research Center of Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia named after Academician V.I. Kulakov.
117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +79164639867. E-mail: n_starodubtseva@oparina4.ru
Kononikhin Alexey Sergeevich, PhD, Researcher of Laboratory of Proteomics and Metabolomics of Human Reproduction, National Medical Research Center of Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia named after Academician V.I. Kulakov.
117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +79167854781. E-mail: konoleha@yandex.ru
Salimova Dinara Failevna, specialist of Laboratory of Proteomics and Metabolomics of Human Reproduction, National Medical Research Center of Obstetrics,
Gynecology and Perinatology, Ministry of Health of Russia named after Academician V.I. Kulakov.
117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +79162060766. E-mail: Salimova.1993@mail.ru
Tokareva Alisa Olegovna, postgraduate student, Moscow Institute of physics and technology.
141700, Russia, Moscow Region, Dolgoprudny, Institutsky lane 9. Tel.: +79651286886. E-mail: alisa.tokareva@phystech.edu
Lagutin Vadim Vladimirovich, Researcher of Bioinformatics Laboratory, National Medical Research Center of Obstetrics, Gynecology and Perinatology,
Ministry of Health of Russia named after Academician V.I. Kulakov. 117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +74991378258. E-mail: laggi@mail.ru
Naumov Vladimir Aleksandrovich, researcher of Bioinformatics Laboratory, National Medical Research Center of Obstetrics, Gynecology and Perinatology,
Ministry of Health of Russia named after Academician V.I. Kulakov. 117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +74991378258. E-mail: looongdog@gmail.com
Nazarova Niso Mirzoevna, MD, PhD, Senior Researcher, National Medical Research Center of Obstetrics, Gynecology and Perinatology,
Ministry of Health of Russia named after Academician V.I. Kulakov. 117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +74954381403. E-mail: grab2@yandex.ru
Frankevich Vladimir Evgenievich, PhD, Head of Department of Systems Biology in Reproduction, National Medical Research Center of Obstetrics,
Gynecology and Perinatology, Ministry of Health of Russia named after Academician V.I. Kulakov.
117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +74954380788, ext. 2198. E-mail: v_frankevich@oparina4.ru
Sukhikh Gennadiy Tikhonovich, Academician of RAMS, MD, PhD, Professor, Director, National Medical Research Center of Obstetrics, Gynecology and Perinatology,
Ministry of Health of Russia named after Academician V.I. Kulakov. 117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +74954381800. E-mail: g_sukhikh@oparina4.ru
For citations: Nekrasova M.E., Chagovets V.V., Starodubtseva N.L., Kononikhin A.S., Salimova D.F., Tokareva A.O., Lagutin V.V., Naumov V.A., Nazarova N.M., Frankevich V.E., Sukhikh G.T. Lipid markers of cervical epithelium neoplastic transformation in HPV-associated diseases. Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2018; (4): 64-70. (in Russian)
https://dx.doi.org/10.18565/aig.2018.4.64-70
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