medgenМедицинская генетикаMedical Genetics2073-7998Publishing House «Genius Media» LLC10.25557/2073-7998.2025.11.12-18medgen-3291Research ArticleОРИГИНАЛЬНОЕ ИССЛЕДОВАНИЕORIGINAL ARTICLEДинамика эпигенетического индекса стволовых клеток как фактор прогноза безметастатической выживаемости после неоадъювантной химиотерапии рака молочной железыDynamics of the epigenetic index of stem cells as a prognostic factor for metastasis-free survival after neoadjuvant chemotherapy for breast cancerКалинкинА. И.KalinkinA. I.

115522, Москва, ул. Москворечье, д. 1

1, Moskvorechye st., Moscow, 115522

СигинВ. О.SiginV. O.

115522, Москва, ул. Москворечье, д. 1

1, Moskvorechye st., Moscow, 115522

НиколаеваА. Ф.NikolaevaA. F.

115522, Москва, ул. Москворечье, д. 1

1, Moskvorechye st., Moscow, 115522

ИбрагимоваМ. К.IbragimovaM. K.

634009, Томск, пер. Кооперативный, д. 5

5, Kooperativny st., Tomsk, 634009

ЦыгановМ. М.TsyganovM. M.

634009, Томск, пер. Кооперативный, д. 5

5, Kooperativny st., Tomsk, 634009

ЛитвяковН. В.LitviakovN. V.

634009, Томск, пер. Кооперативный, д. 5

5, Kooperativny st., Tomsk, 634009

СтрельниковВ. В.StrelnikovV. V.

Стрельников Владимир Викторович

115522, Москва, ул. Москворечье, д. 1

Vladimir V. Strelnikov

1, Moskvorechye st., Moscow, 115522

vstrel@list.ruФГБНУ Медико-генетический научный центр имени академика Н.П. БочковаРоссияResearch Centre for Medical GeneticsRussian FederationНаучно-исследовательский институт онкологии, Томский национальный исследовательский медицинский центр Российской академии наукРоссияCancer Research Institute, Tomsk National Research Medical Center, Russian Academy of SciencesRussian Federation20252412202524111218Copyright © Калинкин А.И., Сигин В.О., Николаева А.Ф., Ибрагимова М.К., Цыганов М.М., Литвяков Н.В., Стрельников В.В., 20252025Калинкин А.И., Сигин В.О., Николаева А.Ф., Ибрагимова М.К., Цыганов М.М., Литвяков Н.В., Стрельников В.В.Kalinkin A.I., Sigin V.O., Nikolaeva A.F., Ibragimova M.K., Tsyganov M.M., Litviakov N.V., Strelnikov V.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.medgen-journal.ru/jour/article/view/3291

Внутриопухолевая клеточная гетерогенность и, особенно, наличие субпопуляции раковых стволовых клеток (РСК), ассоциируются с резистентностью к терапии и метастазированием. Сохранение доли РСК после неоадъювантной химиотерапии (НАХТ) подчёркивает необходимость оценки прогностического потенциала динамики эпигенетического индекса стволовых клеток (ЭИСК) в контексте безметастатической выживаемости у пациенток с раком молочной железы (РМЖ) люминального B подтипа.

На основании данных бисульфитного секвенирования из открытых источников был сформирован референсный эпигенетический атлас, включающий 88 образцов различных клеточных и тканевых типов. С использованием энтропии Шеннона и критерия Уилкоксона были отобраны 45 высоковариабельных CpG-пар для эпигенетической деконволюции. Статистический анализ и деконволюция проведены на 19 парных образцах РМЖ люминального B подтипа до и после НАХТ. Установлено, что исходно высокий уровень ЭИСК в биоптатах РМЖ до лечения ассоциируется с отсутствием метастазирования в течение 10 лет (p < 0,05). После НАХТ в группе без метастазирования наблюдалось значимое снижение ЭИСК в опухолях, тогда как в группе с метастазированием динамика снижения ЭИСК была значительно менее выраженной (p < 0,05). Таким образом, динамика ЭИСК, определяемая методом эпигенетической деконволюции, может рассматриваться в качестве перспективного прогностического и предиктивного маркера при оценке эффективности и исходов НАХТ у пациенток с РМЖ люминального B подтипа.

Intratumoral heterogeneity, particularly the subpopulation of cancer stem cells (CSCs), is associated with therapy resistance and metastasis. The persistence of a small fraction of CSCs after neoadjuvant chemotherapy (NAC) underscores the need to evaluate the prognostic potential of the dynamic epigenetic stem cell index (ESCI) in the context of metastasis-free survival in patients with luminal B subtype breast cancer. Based on bisulfite sequencing data from public repositories, we constructed a reference epigenetic atlas comprising 88 samples of various cell and tissue types. Using Shannon entropy and the Wilcoxon test, 45 highly variable CpG pairs were selected and applied for epigenetic deconvolution. Statistical analysis and deconvolution were performed on 19 paired luminal B breast cancer samples collected before and after NAC. We found that a high baseline ESCI prior to treatment was associated with 10-year metastasis-free survival (p < 0.05). Following NAC, a significant reduction in ESCI was observed in the non-metastatic group, whereas the metastatic group retained baseline ESCI levels. Importantly, the dynamic reduction of ESCI in non-metastatic samples correlated significantly with improved metastasis-free survival (p < 0.05). Thus, ESCI dynamics determined by epigenetic deconvolution may serve as a promising prognostic and predictive biomarker for assessing the efficacy and outcomes of NAC in patients with luminal B breast cancer.

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The authors declare that there are no conflicts of interest present.