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RU2015103190A - METHOD FOR ASSESSING THE RISK OF PROGRESSING INTRAEPITITAL CERVICAL NEOPLASIA AND THE DEVELOPMENT OF Cervical Cancer ON THE BASIS OF DETERMINING HUMAN GENE mRNA LEVELS - Google Patents

METHOD FOR ASSESSING THE RISK OF PROGRESSING INTRAEPITITAL CERVICAL NEOPLASIA AND THE DEVELOPMENT OF Cervical Cancer ON THE BASIS OF DETERMINING HUMAN GENE mRNA LEVELS Download PDF

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RU2015103190A
RU2015103190A RU2015103190A RU2015103190A RU2015103190A RU 2015103190 A RU2015103190 A RU 2015103190A RU 2015103190 A RU2015103190 A RU 2015103190A RU 2015103190 A RU2015103190 A RU 2015103190A RU 2015103190 A RU2015103190 A RU 2015103190A
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Ольга Владимировна Бурменская
Вера Николаевна Прилепская
Нисо Мирзоевна Назарова
Денис Владимирович Ребриков
Дмитрий Юрьевич Трофимов
Геннадий Тихонович Сухих
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Федеральное государственное бюджетное учреждение "Научный центр акушерства, гинекологии и перинатологии имени академика В.И. Кулакова" Министерства здравоохранения Российской Федерации
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Abstract

Способ оценки риска прогрессирования интраэпителиальной цервикальной неоплазии и развития рака шейки матки на основе определения уровней мРНК генов человека, отличающийся тем, что измеряют уровень мРНК генов человека MKI67, CDKN2A или используют любые другие маркеры пролиферации и регуляции клеточного цикла, изменение уровня экспрессии которых при прогрессировании интраэпителиальной цервикальной неоплазии и развитии рака шейки матки коррелирует с уровнем экспрессии MKI67, CDKN2A, в частности CCNB1, BIRC5, AURKA; BCL2 или используют любые другие маркеры апоптоза, изменение уровня экспрессии которых при прогрессировании интраэпителиальной цервикальной неоплазии и развитии рака шейки матки коррелирует с уровнем экспрессии BCL2, в частности BAX, BAG1, NDRG1; PGR или используют любые другие маркеры рецепторного аппарата клеток, изменение уровня экспрессии которых при прогрессировании интраэпителиальной цервикальной неоплазии и развитии рака шейки матки коррелирует с уровнем экспрессии PGR, в частности ESR1, CD68, в образцах из мест поражений и полученные в ходе реакции значения уровней мРНК подставляют в формулу,где p - риск неопластической трансформации;z - значение регрессионной функции, определяют по формулеz=b1*Х1+b2*Х2+…+bn*Xn+а,где X1…Xn - уровень экспрессии мРНК генов или индекс соотношения уровня экспрессии генов; b1…bn - регрессионные коэффициенты; а - константа; при этом если значение p менее или равно пороговому значению (p≤cut-off), делают заключение об отсутствии риска малигнизации; если значение p>cut-off,делают заключение о прогрессии заболевания и высоком риске неопластической трансформации; пороговое значение определяют на основе экспериментальных данных с помощью ROC-анализа.A method for assessing the risk of progression of intraepithelial cervical neoplasia and the development of cervical cancer based on the determination of human gene mRNA levels, characterized in that the mRNA levels of human genes MKI67, CDKN2A are measured or any other markers of cell cycle proliferation and regulation are used, changes in the expression level of which with the progression of intraepithelial cervical neoplasia and the development of cervical cancer correlates with the expression level of MKI67, CDKN2A, in particular CCNB1, BIRC5, AURKA; BCL2 or use any other markers of apoptosis, the change in the expression level of which with the progression of intraepithelial cervical neoplasia and the development of cervical cancer correlates with the expression level of BCL2, in particular BAX, BAG1, NDRG1; PGR or use any other markers of the receptor apparatus of cells, the change in the expression level of which with the progression of intraepithelial cervical neoplasia and the development of cervical cancer correlates with the expression level of PGR, in particular ESR1, CD68, in the samples from the lesion sites and the values of mRNA obtained during the reaction are substituted into the formula, where p is the risk of neoplastic transformation; z is the value of the regression function, is determined by the formula z = b1 * X1 + b2 * X2 + ... + bn * Xn + a, where X1 ... Xn is the level of expression of the gene mRNA or the index of the ratio of the level of ex gene pressures; b1 ... bn - regression coefficients; a is a constant; in this case, if the p value is less than or equal to the threshold value (p≤cut-off), conclude that there is no risk of malignancy; if the value p> cut-off, make a conclusion about the progression of the disease and the high risk of neoplastic transformation; the threshold value is determined on the basis of experimental data using ROC analysis.

Claims (1)

Способ оценки риска прогрессирования интраэпителиальной цервикальной неоплазии и развития рака шейки матки на основе определения уровней мРНК генов человека, отличающийся тем, что измеряют уровень мРНК генов человека MKI67, CDKN2A или используют любые другие маркеры пролиферации и регуляции клеточного цикла, изменение уровня экспрессии которых при прогрессировании интраэпителиальной цервикальной неоплазии и развитии рака шейки матки коррелирует с уровнем экспрессии MKI67, CDKN2A, в частности CCNB1, BIRC5, AURKA; BCL2 или используют любые другие маркеры апоптоза, изменение уровня экспрессии которых при прогрессировании интраэпителиальной цервикальной неоплазии и развитии рака шейки матки коррелирует с уровнем экспрессии BCL2, в частности BAX, BAG1, NDRG1; PGR или используют любые другие маркеры рецепторного аппарата клеток, изменение уровня экспрессии которых при прогрессировании интраэпителиальной цервикальной неоплазии и развитии рака шейки матки коррелирует с уровнем экспрессии PGR, в частности ESR1, CD68, в образцах из мест поражений и полученные в ходе реакции значения уровней мРНК подставляют в формулуA method for assessing the risk of progression of intraepithelial cervical neoplasia and the development of cervical cancer based on the determination of human gene mRNA levels, characterized in that the mRNA levels of human genes MKI67, CDKN2A are measured or any other markers of cell cycle proliferation and regulation are used, changes in the expression level of which with the progression of intraepithelial cervical neoplasia and the development of cervical cancer correlates with the expression level of MKI67, CDKN2A, in particular CCNB1, BIRC5, AURKA; BCL2 or use any other markers of apoptosis, the change in the expression level of which with the progression of intraepithelial cervical neoplasia and the development of cervical cancer correlates with the expression level of BCL2, in particular BAX, BAG1, NDRG1; PGR or use any other markers of the receptor apparatus of cells, the change in the expression level of which with the progression of intraepithelial cervical neoplasia and the development of cervical cancer correlates with the expression level of PGR, in particular ESR1, CD68, in the samples from the lesion sites and the values of mRNA obtained during the reaction are substituted into the formula
Figure 00000001
,
Figure 00000001
,
где p - риск неопластической трансформации;where p is the risk of neoplastic transformation; z - значение регрессионной функции, определяют по формулеz is the value of the regression function, determined by the formula z=b1*Х1+b2*Х2+…+bn*Xn+а, z = b1 * X1 + b2 * X2 + ... + bn * Xn + a, где X1…Xn - уровень экспрессии мРНК генов или индекс соотношения уровня экспрессии генов; b1…bn - регрессионные коэффициенты; а - константа; при этом если значение p менее или равно пороговому значению (p≤cut-off), делают заключение об отсутствии риска малигнизации; если значение p>cut-off,делают заключение о прогрессии заболевания и высоком риске неопластической трансформации; пороговое значение определяют на основе экспериментальных данных с помощью ROC-анализа. where X1 ... Xn is the level of gene mRNA expression or an index of the ratio of the level of gene expression; b1 ... bn - regression coefficients; a is a constant; in this case, if the p value is less than or equal to the threshold value (p≤cut-off), conclude that there is no risk of malignancy; if the value p> cut-off, make a conclusion about the progression of the disease and the high risk of neoplastic transformation; the threshold value is determined on the basis of experimental data using ROC analysis.
RU2015103190A 2015-02-02 2015-02-02 Method for assessing the risk of progression of intraepithelial cervical neoplasia and development of cervical cancer by determining the levels of human mrna genes RU2660360C2 (en)

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