Expression heterogeneity of ABC-transporter family genes and chemosensitivity genes in gastric tumor, carcinomatosis and lymph node metastases
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 effectivene...
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ABV-press
2022-12-01
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| Series: | Успехи молекулярной онкологии |
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| author | M. M. Tsyganov I. A. Tsydenova V. A. Markovich M. K. Ibragimova E. O. Rodionov S. A. Tuzikov N. V. Litvyakov |
| author_facet | M. M. Tsyganov I. A. Tsydenova V. A. Markovich M. K. Ibragimova E. O. Rodionov S. A. Tuzikov N. V. Litvyakov |
| author_sort | M. M. Tsyganov |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-4fbd47404c064e7caa9826a753dfe6ba |
| institution | Kabale University |
| issn | 2313-805X 2413-3787 |
| language | Russian |
| publishDate | 2022-12-01 |
| publisher | ABV-press |
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| series | Успехи молекулярной онкологии |
| spelling | doaj-art-4fbd47404c064e7caa9826a753dfe6ba2025-08-20T03:37:50ZrusABV-pressУспехи молекулярной онкологии2313-805X2413-37872022-12-019410.17650/2313-805X-2022-9-4-78-88264Expression heterogeneity of ABC-transporter family genes and chemosensitivity genes in gastric tumor, carcinomatosis and lymph node metastasesM. M. Tsyganov0I. A. Tsydenova1V. A. Markovich2M. K. Ibragimova3E. O. Rodionov4S. A. Tuzikov5N. V. Litvyakov6Cancer Research Institute of the Tomsk National Research Medical Center of the Russian Academy of Sciences; Siberian State Medical University, Ministry of Health of RussiaCancer Research Institute of the Tomsk National Research Medical Center of the Russian Academy of SciencesCancer Research Institute of the Tomsk National Research Medical Center of the Russian Academy of SciencesCancer Research Institute of the Tomsk National Research Medical Center of the Russian Academy of Sciences; Siberian State Medical University, Ministry of Health of Russia; National Research Tomsk State UniversityCancer Research Institute of the Tomsk National Research Medical Center of the Russian Academy of SciencesCancer Research Institute of the Tomsk National Research Medical Center of the Russian Academy of SciencesCancer Research Institute of the Tomsk National Research Medical Center of the Russian Academy of SciencesIntroduction. 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.https://umo.abvpress.ru/jour/article/view/479disseminated gastric cancercarcinomatosisgenes of the abc transporter familychemosensitivity genestumor heterogeneityexpression |
| spellingShingle | M. M. Tsyganov I. A. Tsydenova V. A. Markovich M. K. Ibragimova E. O. Rodionov S. A. Tuzikov N. V. Litvyakov Expression heterogeneity of ABC-transporter family genes and chemosensitivity genes in gastric tumor, carcinomatosis and lymph node metastases Успехи молекулярной онкологии disseminated gastric cancer carcinomatosis genes of the abc transporter family chemosensitivity genes tumor heterogeneity expression |
| title | Expression heterogeneity of ABC-transporter family genes and chemosensitivity genes in gastric tumor, carcinomatosis and lymph node metastases |
| title_full | Expression heterogeneity of ABC-transporter family genes and chemosensitivity genes in gastric tumor, carcinomatosis and lymph node metastases |
| title_fullStr | Expression heterogeneity of ABC-transporter family genes and chemosensitivity genes in gastric tumor, carcinomatosis and lymph node metastases |
| title_full_unstemmed | Expression heterogeneity of ABC-transporter family genes and chemosensitivity genes in gastric tumor, carcinomatosis and lymph node metastases |
| title_short | Expression heterogeneity of ABC-transporter family genes and chemosensitivity genes in gastric tumor, carcinomatosis and lymph node metastases |
| title_sort | expression heterogeneity of abc transporter family genes and chemosensitivity genes in gastric tumor carcinomatosis and lymph node metastases |
| topic | disseminated gastric cancer carcinomatosis genes of the abc transporter family chemosensitivity genes tumor heterogeneity expression |
| url | https://umo.abvpress.ru/jour/article/view/479 |
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