Tumors of female reproductive system

Опухоли женской репродуктивной системы

1994-40981999-8627

Publishing House ABV Press

779

10.17650/1994-4098-2020-16-4-66-75

GYNECOLOGY. ORIGINAL REPORTS

ГИНЕКОЛОГИЯ. ОРИГИНАЛЬНЫЕ СТАТЬИ

Prognostic value of microRNA assessment in cervical epithelial cells of patients with mild dysplasia

Прогностическое значение анализа микроРНК в клетках цервикального эпителия при дисплазии легкой степени

https://orcid.org/0000-0002-2079-5061

Knyazeva

M. S.

Князева

М. С.

Russian Federation

68 Leningradskaya St., Pesochnyy, Saint Petersburg 197758

4/9 office 16, Lugovaya St., Innovation center “Skolkovo”, Moscow 143026

197758 Санкт-Петербург, пос. Песочный, ул. Ленинградская, 68

143026 Москва, инновационный центр «Сколково», ул. Луговая, 4, стр. 9, пом. 16

Prisyazhnaya

Т. S.

Присяжная

Т. С.

Russian Federation

47 Piskarevskiy Prospekt, Saint Petersburg 195067

195067 Санкт-Петербург, Пискарёвский проспект, 47

https://orcid.org/0000-0003-0827-1641

Zabegina

L. M.

Забегина

Л. М.

Russian Federation

68 Leningradskaya St., Pesochnyy, Saint Petersburg 197758

4/9 office 16, Lugovaya St., Innovation center “Skolkovo”, Moscow 143026

197758 Санкт-Петербург, пос. Песочный, ул. Ленинградская, 68

143026 Москва, инновационный центр «Сколково», ул. Луговая, 4, стр. 9, пом. 16

https://orcid.org/0000-0003-1140-6578

Smirnova

О. A.

Смирнова

О. А.

Russian Federation

68 Leningradskaya St., Pesochnyy, Saint Petersburg 197758

197758 Санкт-Петербург, пос. Песочный, ул. Ленинградская, 68

https://orcid.org/0000-0002-3396-125X

Mikhetko

A. A.

Михетько

А. А.

Russian Federation

47 Piskarevskiy Prospekt, Saint Petersburg 195067

197758 Санкт-Петербург, пос. Песочный, ул. Ленинградская, 68

https://orcid.org/0000-0001-6937-2740

Berlev

I. V.

Берлев

И. В.

Russian Federation

68 Leningradskaya St., Pesochnyy, Saint Petersburg 197758

47 Piskarevskiy Prospekt, Saint Petersburg 195067

197758 Санкт-Петербург, пос. Песочный, ул. Ленинградская, 68

195067 Санкт-Петербург, Пискарёвский проспект, 47

https://orcid.org/0000-0001-5334-7292

Malek

A. V.

Малек

А. В.

Russian Federation

47 Piskarevskiy Prospekt, Saint Petersburg 195067

4/9 office 16, Lugovaya St., Innovation center “Skolkovo”, Moscow 143026

Анастасия Валерьевна Малек

197758 Санкт-Петербург, пос. Песочный, ул. Ленинградская, 68

143026 Москва, инновационный центр «Сколково», ул. Луговая, 4, стр. 9, пом. 16

anastasia@malek.com

N.N. Petrov National Research Institute of Oncology, Ministry of Health of RussiaФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Петрова» Минздрава России

Oncosystem LLCООО «Онкосистема»

I.I. Mechnikov North-Western State Medical University, Ministry of Health of RussiaФГБОУ ВО «Северо-Западный государственный медицинский университет им. И.И. Мечникова» Минздрава России

13122020

164

66751203202112032021

2020

https://ojrs.abvpress.ru/ojrs/article/view/779

Background. Currently, there are no reliable markers for the prognosis of the low-grade squamous intraepithelial lesion (LSIL) of the cervical epithelium. Scientific literature provides with inconsistent recommendations regarding the management of the young patients with a cytological diagnosis of LSIL. The progression of cervical dysplasia and the development of cervical cancer are associated with characteristic alterations of the microRNA expression profile.

Objective: to assess the prognostic value of microRNA in LSIL. Materials and methods. Samples (cytological smears) obtained from patients diagnosed with LSIL (n = 36), but with a different course of the disease over the next 6–12 months. Analysis of miRNA expression was carried out by the method of “two-tailed” reverse transcription and subsequent PCR.

Results. The expression level of miR-126, miR-21, miR-1246, miR-182 was statistically significantly different in the compared groups, but the predictive value of the analysis of individual molecules was low (AUC <0.65). Calculation of the concentration ratios of the “reciprocal” pairs of microRNAs made it possible to obtain a more effective prognostic marker. ROC analysis of such ratios (miR-126/miR-182, miR-21/miR-182, miR-1246/miR-182) yielded AUC values: 0.82–0.89, sensitivity: 0.71–0.92; specificity: 0.86.

Conclusions. Analysis of a panel of microRNA marker molecules in the material of the cervical epithelium and calculation of the concentration ratios of “reciprocal” pairs is a promising method for prognosis of LSIL course.

Введение. В настоящее время не существует надежных маркеров прогноза течения дисплазии цервикального эпителия легкой степени (low-grade squamous intraepithelial lesion, LSIL). В научной литературе представлены разноречивые рекомендации относительно тактики ведения пациенток молодого возраста с цитологическим диагнозом LSIL. Прогрессирование дисплазии и развитие рака шейки матки ассоциированы с характерными изменениями профиля экспрессии микроРНК в клетках цервикального эпителия.

Цель исследования – оценить прогностическое значение микроРНК клеток цервикального эпителия при LSIL.

Материалы и методы. Материалами исследования служили образцы (цитологические мазки), полученные от пациенток с диагнозом LSIL (n = 36), но с разным течением заболевания в течение последующих 6–12 мес. Анализ экспрессии микроРНК был проведен методом «двухфланговой» обратной транскрипции и последующей полимеразной цепной реакции.

Результаты. Уровни экспрессии miR-126, miR-21, miR-1246, miR-182 статистически значимо различались в сравниваемых группах, но прогностическая значимость анализа отдельных молекул была низкой (AUC <0,65). Расчет соотношений концентраций реципрокных пар микроРНК позволил повысить прогностическую значимость анализа. При ROC-анализе таких соотношений (miR-126/miR-182, miR-21/miR-182, miR-1246/miR-182) получены следующие значения: AUC 0,82–0,89; чувствительность 0,71–0,92; специфичность 0,86.

Выводы. Анализ панели маркерных молекул микроРНК в материале цервикального эпителия и расчет соотношений концентраций реципрокных пар является перспективным методом прогноза течения LSIL.

cervical cancerlow-grade squamous intraepithelial lesionprognosismicroRNAreverse transcription polymerase chain reaction

рак шейки маткидисплазия легкой степенипрогнозмикроРНКполимеразная цепная реакция с обратной транскрипцией

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