Volume 15, Issue 58 (4-2025)
NCMBJ 2025, 15(58): 81-93 |
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Arjmandi K, Salahshouri I, Ameli F, Irani S, Esfandbod O. Investigating the clinical relevance of variants in the 5′ UTR region of the TYMS gene in response to chemotherapy in Iranian gastric cancer patients. NCMBJ 2025; 15 (58) :81-93
URL: http://ncmbjpiau.ir/article-1-1743-en.html
URL: http://ncmbjpiau.ir/article-1-1743-en.html
Department of Biology, SR.C.,Islamic Azad University , Tehran , Iran , isalahshouri@gmail.com
Abstract: (209 Views)
Aim and Background: Genetic variants are valuable markers for predicting chemotherapy resistance. Thymidylate synthetase is an important enzyme target in gastric cancer patients treated with neoadjuvant 5-fluorouracil-based chemotherapy. Genetic variants in the thymidylate synthetase gene are effective in gene expression and resistance to chemotherapy in gastric cancer patients. Therefore, the aim of this study is to investigate the variants of the TYMS gene and the possible effect of their alleles on drug resistance, survival, and gene expression in gastric cancer patients.
Materials and Methods: Genetic analysis was performed on normal sections of paraffin blocks of 100 patients. All patients received neoadjuvant chemotherapy based on 5-fluorouracil. The genotypes of rs34743033 (TYMS 28-bp VNTR) and rs2853542 (TYMS SNP C>G) variants were determined, and gene expression was investigated in tumor tissue and tumor margins of patients
Results: A significant association between TYMS 28 bp VNTR genotypes and treatment was observed (P=0.003). Patients with the 2R3R genotype showed a better response to treatment. The highest and lowest survival times were observed for the 3R3R and 2R2R genotypes, respectively (P=0.003). There was a significant relationship between gene expression and the TYMS 28 bp VNTR variant and the TYMS SNP C>G variant (P<0.001). The CC genotype of the TYMS SNP C>G variant was associated with lower gene expression and the CG genotype was associated with higher gene expression.
Conclusion: This study showed that determining the genotypes and expression of the TYMS gene can be effective for predicting the survival of gastric cancer patients and their response to 5-fluorouracil-based chemotherapy.
Materials and Methods: Genetic analysis was performed on normal sections of paraffin blocks of 100 patients. All patients received neoadjuvant chemotherapy based on 5-fluorouracil. The genotypes of rs34743033 (TYMS 28-bp VNTR) and rs2853542 (TYMS SNP C>G) variants were determined, and gene expression was investigated in tumor tissue and tumor margins of patients
Results: A significant association between TYMS 28 bp VNTR genotypes and treatment was observed (P=0.003). Patients with the 2R3R genotype showed a better response to treatment. The highest and lowest survival times were observed for the 3R3R and 2R2R genotypes, respectively (P=0.003). There was a significant relationship between gene expression and the TYMS 28 bp VNTR variant and the TYMS SNP C>G variant (P<0.001). The CC genotype of the TYMS SNP C>G variant was associated with lower gene expression and the CG genotype was associated with higher gene expression.
Conclusion: This study showed that determining the genotypes and expression of the TYMS gene can be effective for predicting the survival of gastric cancer patients and their response to 5-fluorouracil-based chemotherapy.
Type of Study: Research Article |
Subject:
Cellular and molecular
Received: 2025/04/29 | Accepted: 2025/04/3 | Published: 2025/04/3
Received: 2025/04/29 | Accepted: 2025/04/3 | Published: 2025/04/3
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