Diagnosis of squamous intraepithelial lesions and cervical cancer based on the quantitative assessment of microRNA expression
Objective. To estimate the possibility of differential diagnosis of the severity of cervical squamous intraepithelial lesions on the basis of quantitative assessment of microRNA expression: has-mir-22-3p, has-mir-25*-3p, and has-mir-92a-5p in cervical epithelial scrapings.Chernova V.F., Karnaukhov V.N., Faizullin L.Z., Bairamova G.R., Kogan E.A., Mzarelua G.M., Nazarova N.M., Kozachenko A.V., Trofimov D.Yu., Prilepskaya V.N., Sukhikh G.T.
Subjects and methods. The investigation enrolled 95 women aged 18 to 49 years (mean age, 32.7±0.5 years) who were divided into 4 groups: 1) 32 patients without cervical disease; 2) 31 patients with low-grade squamous intraepithelial lesion; 3) 26 patients with high-grade squamous intraepithelial lesion; 4) 6 patients with cervical cancer. For a clinical diagnosis, cytological and histological examinations, extended colposcopy, and HPV testing were used and the level of microRNA expression was measured by quantitative real-time PCR.
Results. In cervical squamous intraepithelial lesions, the synthesis of mir-22 was considerably decreased and the expression of mir-92a was, on the contrary, increased. The expression of mir-25 was elevated insignificantly. A logistic regression analysis could reveal the mir-22 and mir-92a expression thresholds that allowed the differentiation of cervical cancer with a diagnostic accuracy of more than 80% in both patients without visible abnormalities and those with squamous intraepithelial lesions.
Conclusion. Along with traditional methods, the investigation permits the expression level of miRNAs, mir-22, and mir-92a to be considered as an informative molecular marker to predict the extent of involvement of the cervical epithelium in pre-cancer and cancer of the cervix uteri.
Keywords
cervical intraepithelial neoplasia
squamous intraepithelial lesions
cervical cancer
mir-22
mir-25
mir-92a
expression
References
1. Torre L.A., Bray F., Siegel R.L., Ferlay J., Lortet-Tieulent J., Jemal A. Global cancer statistics, 2012. CA: Cancer J. Clin. 2015; 65(2): 87-108.
2. Bernard E., Pons-Salort M., Favre M., Heard I., Delarocque-Astagneau E., Guillemot D., Thiébaut A.C. Comparing human papillomavirus prevalences in women with normal cytology or invasive cervical cancer to rank genotypes according to their oncogenic potential: A meta-analysis of observational studies. BMC Infect. Dis. 2013; 13: 373.
3. Давыдов М.И., Аксель Е.М. ред. Статистика злокачественных новообразований в России и странах СНГ в 2012 г. М.: Издательская группа РОНЦ; 2014: 47. [Davydov M.I., Axel E.M., ed. Statistics of malignant neoplasms in Russia and CIS countries in 2012. Moscow: Publishing group RONTS; 2014: 47. (in Russian)]
4. DiGiuseppe S., Keiffer T.R., Bienkowska-Haba M., Luszczek W., Guion L.G., Müller M., Sapp M. Topography of the human papillomavirus minor capsid protein L2 during vesicular trafficking of infectious entry. J. Virol. 2015; 89(20): 10442-52.
5. Richart R.M. Cervical intraepithelial neoplasia. Pathol. Ann. 1973; 8: 301.
6. World Health Organization. Human papillomavirus (HPV) and cervical cancer. Available at: http://www.who.int/mediacentre/factsheets/fs380/en/Accessed 24 February 2016
7. Stahlhut C., Slack F.J. MicroRNAs and the cancer phenotype: profiling, signatures and clinical implications. Genome Med. 2013; 5(12): 111.
8. Frixa T., Donzelli S., Blandino G. Oncogenic MicroRNAs: Key players in malignant transformation. Cancers (Basel). 2015; 7(4): 2466-85.
9. Galamb Á., Benczik M., Zinner B., Vígh E., Baghy K., Jeney C. et al. Dysregulation of microRNA expression in human cervical preneoplastic and neoplastic lesions. Pathol. Oncol. Res. 2015; 21(3): 503-8.
10. Коган Е.А., Файзуллина Н.М., Ли Ц., Демура Т.А., Жарков Н.В., Козаченко А.В., Чернова В.Ф., Байрамова Г.Р., Прилепская В.Н. Ранняя диагностика ВПЧ-ассоциированной патологии шейки матки у женщин до 30 лет и старше. Акушерство и гинекология. 2015; 9: 62-7. [Kogan E.A., Faizullina N.M., Li Ts., Demura T.A., Zharkov N.V., Kozachenko A.V., Chernova V.F., Bairamova G.R., Prilepskaya V.N. Early diagnosis of HPV-associated disease of the cervix uteri in women aged less than 30 years or older. Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2015; (9): 62-7. (in Russian)]
11. Zhu X.L., Wen S.Y., Ai Z.H., Wang J., Xu Y.L., Teng Y.C. Screening for characteristic microRNAs between pre-invasive and invasive stages of cervical cancer. Mol. Med. Rep. 2015; 12(1): 55-62.
12. Chen C., Ridzon D.A., Broomer A.J., Zhou Z., Lee D.H., Nguyen J.T. et al. Realtime quantification of microRNAs by stem-loop RT-PCR. Nucleic Acids Res. 2005; 33(20): e179.
13. López A.Y., López J.A. Multistep model of cervical cancer: participation of miRNAs and coding genes. Int. J. Mol. Sci. 2014; 15(9): 15700-33.
14. Байрамова Г.Р., Файзуллин Л.З., Королькова А.И., Полозников А.А., Киселев В.И. Скрининг рака шейки матки: что нового в мировой практике? Акушерство и гинекология. 2016; 7: 17-21. http://dx.doi.org/10.18565/aig.2016.7.17-21 [Bairamova G.R., Faizullin L.Z., Korolkova A.I., Poloznikov A.A., Kiselev V.I. Cervical cancer screening: What is new in global practice? Akusherstvo i ginekologiya/Obstetrics and Gynecology. 2016; (7): 17-21. (in Russian) http://dx.doi.org/10.18565/aig.2016.7.17-21]
15. Tian Q., Li Y., Wang F., Li Y., Xu J., Shen Y. et al. MicroRNA Detection in cervical exfoliated cells as a triage for human papillomavirus – positive women. J. Natl. Cancer Inst. 2014; 106(9): pii: dju241.
16. Malta M., Ribeiro J., Monteiro P., Loureiro J., Medeiros R., Sousa H. Let-7c is a candidate biomarker for cervical intraepithelial lesions: a pilot study. Mol. Diagn. Ther. 2015; 19(3): 191-6.
17. Xin M., Qiao Z., Li J., Liu J., Song S., Zhao X. et al. miR-22 inhibits tumor growth and metastasis by targeting ATP citrate lyase: evidence in osteosarcoma, prostate cancer, cervical cancer and lung cancer. Oncotarget. 2016; 7(28):44252-65.
18. Song S.J., Pandolfi P.P. miR-22 in tumorigenesis. Cell Cycle. 2014; 13(1): 11-2.
19. Zhang H., Cao H., Xu D., Zhu K. MicroRNA-92a promotes metastasis of nasopharyngeal carcinoma by targeting the PTEN/AKT pathway. Onco Targets Ther. 2016; 9: 3579-88.
20. Caiazza C., Mallardo M. The roles of miR-25 and its targeted genes in development of human cancer. Microna. 2016; 5(2): 113-9.
Received 10.04.2017
Accepted 28.04.2017
About the Authors
Viktoria Chernova, PhD student of the Research Center of Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia. 117997, Russia, Moscow, Ac. Oparina 4Vitaly Nikolaevich Karnaukhov, Junior Researcher, Laboratory of Molecular Genetic Methods, Research Center of Obstetrics, Gynecology and Perinatology,
Ministry of Health of Russia. 117997, Russia, Moscow, Ac. Oparina 4. Tel.: +79167106789. E-mail: v_karnauhov@oparina4.ru
Fayzullin Leonid Zakievich, Cand. Sc. (Biology), Leading Researcher, Laboratory of Molecular Genetic Methods, Research Center of Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia. 117997, Russia, Moscow, Ac. Oparina 4. Tel.: +79167106789. E-mail: l_faizullin@oparina4.ru
Bayramova Guldana Raufovna, doctor of medical sciences, head of the clinical work of the scientific and polyclinic department, Research Center of Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia. 117997, Russia, Moscow, Ac. Oparina 4. Tel.: +79099947700. E-mail: g_bairamova@oparina4.ru
Kogan Evgenia Aleksandrovna, MD, Professor, Head of the Department of Pathological Anatomy, I.M. Sechenov First Moscow State Medical University.
119991, Russia, Moscow, Bolshaya Pirogovskaya st. 2-4. Tel.: +79265331271. E-mail: koganevg@gmail.com
Mzarelua Guranda Merabovna, graduate student of the Research Center of Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia.
117997, Russia, Moscow, Ac. Oparina 4. Tel.: +74954381403. E-mail: mzareluag@mail.ru
Nazarova Niso Mirzoevna, doctor of medical sciences, leading researcher of the scientific and polyclinic department, Research Center of Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia. 117997, Russia, Moscow, Ac. Oparina 4. Tel.: +74954381403. E-mail: n_nazarova@oparina4.ru
Kozachenko Andrey Vladimirovich, leading research assistant of the gynecological department, Research Center of Obstetrics, Gynecology and Perinatology,
Ministry of Health of Russia. 117997, Russia, Moscow, Ac. Oparina 4. Tel.: +74954387783. E-mail: a_kozachenko@oparina4.ru
Dmitriy Trofimov, Doctor of Biological Sciences, Head of the Laboratory of Molecular Genetic Methods, Research Center of Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia. 117997, Russia, Moscow, Ac. Oparina 4. Tel.: +79166144922. E-mail: d_trofimov@oparina4.ru
Prilepskaya Vera Nikolaevna, doctor of medical sciences, deputy director for science, Research Center of Obstetrics, Gynecology and Perinatology,
Ministry of Health of Russia. 117997, Russia, Moscow, Ac. Oparina 4. Tel.: +74954386934
Sukhikh Gennady Tikhonovich, Doctor of Medical Sciences, Academician of the Russian Academy of Sciences, Director of the Research Center of Obstetrics,
Gynecology and Perinatology, Ministry of Health of Russia. 117997, Russia, Moscow, Ac. Oparina 4. Tel.: +74954381800. E-mail: g_sukhikh@oparina4.ru
For citations: Chernova V.F., Karnaukhov V.N., Faizullin L.Z., Bairamova G.R.,
Kogan E.A., Mzarelua G.M., Nazarova N.M., Kozachenko A.V., Trofimov D.Yu.,
Prilepskaya V.N., Sukhikh G.T. Diagnosis of squamous intraepithelial lesions and cervical cancer based on the quantitative assessment of microRNA expression.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2017; (9): 78-84. (in Russian)
http://dx.doi.org/10.18565/aig.2017.9.78-84
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