Advances in Molecular Oncology

Успехи молекулярной онкологии

2313-805X2413-3787

Publishing House ABV Press

479

10.17650/2313-805X-2022-9-4-78-88

RESEARCH ARTICLES

ЭКСПЕРИМЕНТАЛЬНЫЕ СТАТЬИ

Expression heterogeneity of ABC-transporter family genes and chemosensitivity genes in gastric tumor, carcinomatosis and lymph node metastases

Экспрессионная гетерогенность генов семейства ABC-транспортеров и генов химиочувствительности в опухоли желудка, канцероматозе и метастазах в лимфатические узлы

https://orcid.org/0000-0001-7419-4512

Tsyganov

M. M.

Цыганов

М. М.

Russian Federation

5 Cooperative Lane, omsk 634009

2 Moskovsky Tract, Tomsk 634050

Матвей Михайлович Цыганов

634009 Томск, переулок Кооперативный, 5

634050 Томск, Московский тракт, 2

TsyganovMM@yandex.ru

https://orcid.org/0000-0002-2716-3075

Tsydenova

I. A.

Цыденова

И. А.

Russian Federation

5 Cooperative Lane, Tomsk 634009

634009 Томск, переулок Кооперативный, 5

https://orcid.org/0000-0002-7599-1211

Markovich

V. A.

Маркович

В. А.

Russian Federation

5 Cooperative Lane, Tomsk 634009

634009 Томск, переулок Кооперативный, 5

https://orcid.org/0000-0001-8815-2786

Ibragimova

M. K.

Ибрагимова

М. К.

Russian Federation

5 Cooperative Lane, Tomsk 634009

2 Moskovsky Tract, Tomsk 634050

36 Lenina Prospekt, Tomsk 634050

634009 Томск, переулок Кооперативный, 5

634050 Томск, Московский тракт, 2

634050 Томск, проспект Ленина, 36

https://orcid.org/0000-0003-4980-8986

Rodionov

E. O.

Родионов

Е. О.

Russian Federation

5 Cooperative Lane, Tomsk 634009

634009 Томск, переулок Кооперативный, 5

https://orcid.org/0000-0002-0884-1838

Tuzikov

S. A.

Тузиков

С. А.

Russian Federation

Cooperative Lane, Tomsk 634009

634009 Томск, переулок Кооперативный, 5

https://orcid.org/0000-0002-0714-8927

Litvyakov

N. V.

Литвяков

Н. В.

Russian Federation

Cooperative Lane, Tomsk 634009

634009 Томск, переулок Кооперативный, 5

Cancer Research Institute of the Tomsk National Research Medical Center of the Russian Academy of SciencesНаучно-исследовательский институт онкологии ФГБНУ «Томский национальный исследовательский медицинский центр Российской академии наук»

Siberian State Medical University, Ministry of Health of RussiaФГБОУ ВО «Сибирский государственный медицинский университет» Минздрава России

National Research Tomsk State UniversityНациональный исследовательский Томский государственный университет

15122022

1712202217122022

2022

Tsyganov M.M., Tsydenova I.A., Markovich V.A., Ibragimova M.K., Rodionov E.O., Tuzikov S.A., Litvyakov N.V.

Цыганов М.М., Цыденова И.А., Маркович В.А., Ибрагимова М.К., Родионов Е.О., Тузиков С.А., Литвяков Н.В.

https://creativecommons.org/licenses/by/4.0

https://umo.abvpress.ru/jour/article/view/479

Introduction. Metastatic tumors (particularly gastric cancer) have been found to be characterized by heterogeneity between the primary tumor and metastases. This type of heterogeneity comes to the fore when treating primary-metastatic forms of tumor and is an important reason for the low effectiveness of their treatment. In this regard, comparative analysis of ABC-transporter gene expression and chemosensitivity genes will allow to characterize to a certain extent the resistance and sensitivity of primary tumor, carcinomatosis and metastases to therapy and provide the basis for personalized treatment approach.Aim. To evaluate expression heterogeneity of ABC-transporter genes and chemosensitivity genes in gastric tumor, carcinomatosis and lymph node metastases.Materials and methods. Overall 41 patients with disseminated gastric cancer stage IV with carcinomatosis of peritoneum were included in the investigation. All patients underwent surgery according to Roux palliative gastrectomy. After surgery patients underwent chemotherapy depending on indications. RNA was isolated using RNeasy Plus mini kit (Qiagen, Germany). The expression level of ABC transporter genes (ABCB1, ABCC1, ABCC2, ABCC5, ABCG1, ABCG2) and chemosensitivity genes (BRCA1, RRM1, ERCC1, TOP1, TOP2α, TUBβ3, TYMS, GSTP1) was assessed by reverse transcription polymerase chain reaction (RT-PCR) in primary tumor, carcinomatosis and lymph node metastases.Results. The expression levels of the genes under study were shown to vary widely. For ABC transporter genes, ABCG1 (3.1 ± 1.1; max 32.0), ABCG2 (7.9 ± 2.3; max 54.1), ABCG2 (9.6 ± 3.8; max 101.0) were the most expressed genes in gastric tumor tissue, carcinomatosis and lymph node metastasis, respectively. Hyperexpression among chemosensitivity genes at all three sites was characteristic only of TOP2α (17.2 ± 6.0; max. 161.9; 10.8 ± 4.1; max. 105.1; 35.3 ± 0.8; max. 439.6, respectively). We found that TOP2α and BRCA1 gene expression levels were higher in lymph node metastasis compared with gastric tumor tissue and carcinomatosis (at p = 0.005 and p = 0.001). Whereas ABCC1 gene expression was statistically significantly higher in carcinomatosis (p = 0.03).Conclusion. Thus, a high level of expression heterogeneity is observed in gastric cancer, which affects the expression patterns of various genes in different localizations. The expression profile can be used to determine the level of heterogeneity and approach to personalized therapy tactics.

Введение. Установлено, что метастатическим опухолям (в частности раку желудка) свойственна гетерогенность между первичными и метастатическими очагами. Такой тип гетерогенности является причиной низкой эффективности терапии, поэтому его следует учитывать при лечении первично-метастатических форм опухоли. В связи с этим сравнительный анализ экспрессии генов ABC-транспортеров и генов химиочувствительности позволит в определенной мере охарактеризовать резистентность и чувствительность первичной опухоли, канцероматоза и метастазов к терапии и дать основу для персонализированного подхода в лечении.Цель – оценка экспрессионной гетерогенности генов ABC-транспортеров и генов химиочувствительности в опухоли желудка, канцероматозе и метастазах в лимфатические узлы.Материалы и методы. В исследование включен 41 больной с диссеминированным раком желудка IV стадии с канцероматозом брюшины. Всем пациентам выполнена операция в объеме паллиативной гастрэктомии по Ру. После хирургического вмешательства в зависимости от показаний проводилась химиотерапия по схемам GemCap + С, FOLFIRI + С, XELIRI + C, PC. РНК выделяли с помощью набора RNeasy Plus mini Kit (Qiagen, Германия). Уровень экспрессии генов ABC-транспортеров (ABCB1, ABCC1, ABCC2, ABCC5, ABCG1, ABCG2) и генов химиочувствительности (BRCA1, RRM1, ERCC1, TOP1, TOP2α, TUBβ3, TYMS, GSTP1) в первичной опухоли, канцероматозе и метастазе в лимфатические узлы оценивали с помощью полимеразной цепной реакции с обратной транскрипцией (ОТ-ПЦР).Результаты. Показано, что уровень экспрессии исследуемых генов сильно варьирует. Из генов ABC-транспортеров наибольшее значение экспрессии для опухолевой ткани желудка, канцероматоза и метастаза в лимфатические узлы выявлено для ABCG1 (3,1 ± 1,1; max 32,0), ABCG2 (7,9 ± 2,3; max 54,1) и ABCG2 (9,6 ± 3,8; max 100,9) соответственно. Среди генов химиочувствительности гиперэкспрессия в этих тканях была характерна только для TOP2α (17,2 ± 5,9; max 161,9; 10,8 ± 4,1; max 105,1; 35,3 ± 0,8; max 439,6 соответственно). Установлено, что уровень экспрессии генов TOP2α и BRCA1 выше в метастазах в лимфатических узлах по сравнению с опухолевой тканью желудка и канцероматозом (p = 0,005 и p = 0,001 соответственно), тогда как экспрессия гена ABCC1 статистически значимо выше в канцероматозе (p = 0,03).Заключение. Таким образом, прослеживается высокий уровень экспрессионной гетерогенности при раке желудка, влияющей на паттерны экспрессии различных генов в разных локализациях. Точное определение профиля экспрессии исследуемых генов в первичной опухоли и метастазах позволит подобрать тактику лечения и схемы химиотерапии, которые с наибольшей вероятностью будут эффективны в каждом конкретном случае.

disseminated gastric cancercarcinomatosisgenes of the ABC transporter familychemosensitivity genestumor heterogeneityexpression

диссеминированный рак желудкаканцероматозгены семейства ABC-транспортеровгены химиочувствительностигетерогенность опухолиэкспрессия

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