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Heydari, Nadia, Saghaeian Jazi, Marie, Asadi, Jahanbakhsh, Sheikh Arabi, Mehdi, Jafari, Seyyed Mehdi. (1405). Overexpression of Cytidine Triphosphate Synthetase 1 (CTPS1) and Deoxythymidylate Kinase (DTYMK) in Patients with Newly Diagnosed Esophageal Squamous Cell Carcinoma. سامانه مدیریت نشریات علمی, (), -. doi: 10.30476/ijms.2026.108824.4388
Nadia Heydari; Marie Saghaeian Jazi; Jahanbakhsh Asadi; Mehdi Sheikh Arabi; Seyyed Mehdi Jafari. "Overexpression of Cytidine Triphosphate Synthetase 1 (CTPS1) and Deoxythymidylate Kinase (DTYMK) in Patients with Newly Diagnosed Esophageal Squamous Cell Carcinoma". سامانه مدیریت نشریات علمی, , , 1405, -. doi: 10.30476/ijms.2026.108824.4388
Heydari, Nadia, Saghaeian Jazi, Marie, Asadi, Jahanbakhsh, Sheikh Arabi, Mehdi, Jafari, Seyyed Mehdi. (1405). 'Overexpression of Cytidine Triphosphate Synthetase 1 (CTPS1) and Deoxythymidylate Kinase (DTYMK) in Patients with Newly Diagnosed Esophageal Squamous Cell Carcinoma', سامانه مدیریت نشریات علمی, (), pp. -. doi: 10.30476/ijms.2026.108824.4388
Heydari, Nadia, Saghaeian Jazi, Marie, Asadi, Jahanbakhsh, Sheikh Arabi, Mehdi, Jafari, Seyyed Mehdi. Overexpression of Cytidine Triphosphate Synthetase 1 (CTPS1) and Deoxythymidylate Kinase (DTYMK) in Patients with Newly Diagnosed Esophageal Squamous Cell Carcinoma. سامانه مدیریت نشریات علمی, 1405; (): -. doi: 10.30476/ijms.2026.108824.4388

Overexpression of Cytidine Triphosphate Synthetase 1 (CTPS1) and Deoxythymidylate Kinase (DTYMK) in Patients with Newly Diagnosed Esophageal Squamous Cell Carcinoma

Iranian Journal of Medical Sciences
مقالات آماده انتشار، اصلاح شده برای چاپ، انتشار آنلاین از تاریخ 07 مهر 1405    اصل مقاله (939.33 K)
نوع مقاله: Original Article(s)
شناسه دیجیتال (DOI): 10.30476/ijms.2026.108824.4388
نویسندگان
Nadia Heydari1، 2؛ Marie Saghaeian Jazi1؛ Jahanbakhsh Asadi1، 2؛ Mehdi Sheikh Arabi3؛ Seyyed Mehdi Jafari* 1، 2
1Metabolic Disorders Research Center, Biomedical Research Institute, Golestan University of Medical Sciences, Gorgan, Iran
2Department of Biochemistry and Biophysics, School of Medicine, Golestan University of Medical Sciences, Gorgan, Iran
3Medical Cellular and Molecular Research Center, Golestan University of Medical Sciences, Gorgan, Iran
چکیده
Background: Increased pyrimidine metabolism is characterized by dysregulation of the rate-limiting enzymes in this pathway, including uridine cytidine kinase 2 (UCK2), deoxythymidylate kinase (DTYMK), and cytidine triphosphate synthetase 1 (CTPS1). Emerging evidence highlighted the critical role of these enzymes in cancer progression. 
Methods: This cross-sectional study was conducted at Golestan University of Medical Sciences (Gorgan, Iran) in 2023. Initially, the Gene Expression database of Normal and Tumor tissue (GENT2) and the OncoDB database were checked to investigate the expression of these genes in esophageal cancer (EC) tissues. Subsequently, 34 pairs of newly diagnosed esophageal squamous cell carcinoma (ESCC) tissues and matched adjacent healthy tissues were collected. Real-time PCR was performed to measure the expression of these genes in the collected tissues. Statistical analyses were performed using SPSS version 22 and GraphPad Prism version 8. The Mann-Whitney test and the Wilcoxon matched-pairs signed-rank test were used to compare gene expression. P<0.05 was considered statistically significant.
Results: The results demonstrated that CTPS1 (1.47 and 0.246-6.964, P=0.035) and DTYMK (1.62 and 0.733-5.278, P=0.009) expression levels in tumor tissue were higher than those in adjacent healthy tissues. The expression level of the UCK2 gene (1.32 and 0.278-3.834, P=0.052) was elevated in tumor tissues compared with surrounding non-tumor tissues. However, this difference was not statistically significant. Furthermore, DTYMK expression was significantly higher in females (3.73 and 1.505-11.313) than in males (0.81 and 
0.213-1.624, P=0.007).
Conclusion: CTPS1 and DTYMK were overexpressed in ESCC tissues compared with adjacent healthy tissue, which could provide valuable insights for the development of ESCC treatment strategies.

تازه های تحقیق

Nadia Heydari (Google Scholar)
Seyyed Mehdi Jafari (Google Scholar) 

کلیدواژه‌ها
CTP synthetase1؛ Deoxythymidylate kinase؛ Esophageal cancer؛ Uridine-cytidine kinase 2؛ Pyrimidine synthesis
مراجع
  1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71:209-49. doi: 10.3322/caac.21660. PubMed PMID: 33538338.
  2. Lyu SI, Fretter C, Hillmer AM, Grothey B, Hoppe S, Simon AG, et al. Basal-like subtype of esophageal adenocarcinoma and it’s morphological, molecular and clinical characteristics. Sci Rep. 2025;15:24680. doi: 10.1038/s41598-025-08721-9. PubMed PMID: 40634392; PubMed Central PMCID: PMC12241421.
  3. Codipilly DC, Wang KK. Squamous Cell Carcinoma of the Esophagus. Gastroenterol Clin North Am. 2022;51:457-84. doi: 10.1016/j.gtc.2022.06.005. PubMed PMID: 36153105.
  4. Liu CQ, Ma YL, Qin Q, Wang PH, Luo Y, Xu PF, et al. Epidemiology of esophageal cancer in 2020 and projections to 2030 and 2040. Thorac Cancer. 2023;14:3-11. doi: 10.1111/1759-7714.14745. PubMed PMID: 36482832; PubMed Central PMCID: PMC9807450.
  5. Ghasemi-Kebria F, Semnani S, Fazel A, Etemadi A, Amiriani T, Naeimi-Tabiei M, et al. Esophageal and gastric cancer incidence trends in Golestan, Iran: An age-period-cohort analysis 2004 to 2018. Int J Cancer. 2023;153:73-82. doi: 10.1002/ijc.34518. PubMed PMID: 36943026.
  6. Collaborators GBDOC. The global, regional, and national burden of oesophageal cancer and its attributable risk factors in 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet Gastroenterol Hepatol. 2020;5:582-97. doi: 10.1016/S2468-1253(20)30007-8. PubMed PMID: 32246941; PubMed Central PMCID: PMC7232026.
  7. Hassanipour S, Mohammadian-Hafshejani A, Ghoncheh M, Salehiniya H. The incidence and mortality of esophageal cancer and its relationship with development in the world. Biomed Res Ther. 2017;4:1607-23. doi: 10.15419/bmrat.v4i9.368.
  8. Martinez-Outschoorn UE, Peiris-Pages M, Pestell RG, Sotgia F, Lisanti MP. Cancer metabolism: a therapeutic perspective. Nat Rev Clin Oncol. 2017;14:11-31. doi: 10.1038/nrclinonc.2016.60. PubMed PMID: 27141887.
  9. Wang W, Cui J, Ma H, Lu W, Huang J. Targeting Pyrimidine Metabolism in the Era of Precision Cancer Medicine. Front Oncol. 2021;11:684961. doi: 10.3389/fonc.2021.684961. PubMed PMID: 34123854; PubMed Central PMCID: PMC8194085.
  10. Yeh HW, Lee SS, Chang CY, Hu CM, Jou YS. Pyrimidine metabolic rate limiting enzymes in poorly-differentiated hepatocellular carcinoma are signature genes of cancer stemness and associated with poor prognosis. Oncotarget. 2017;8:77734-51. doi: 10.18632/oncotarget.20774. PubMed PMID: 29100421; PubMed Central PMCID: PMC5652811.
  11. Wang H, Wang X, Xu L, Zhang J, Cao H. High expression levels of pyrimidine metabolic rate-limiting enzymes are adverse prognostic factors in lung adenocarcinoma: a study based on The Cancer Genome Atlas and Gene Expression Omnibus datasets. Purinergic Signal. 2020;16:347-66. doi: 10.1007/s11302-020-09711-4. PubMed PMID: 32638267; PubMed Central PMCID: PMC7524999.
  12. Fu Y, Wei XD, Guo L, Wu K, Le J, Ma Y, et al. The Metabolic and Non-Metabolic Roles of UCK2 in Tumor Progression. Front Oncol. 2022;12:904887. doi: 10.3389/fonc.2022.904887. PubMed PMID: 35669416; PubMed Central PMCID: PMC9163393.
  13. Wu Y, Jamal M, Xie T, Sun J, Song T, Yin Q, et al. Uridine-cytidine kinase 2 (UCK2): A potential diagnostic and prognostic biomarker for lung cancer. Cancer Sci. 2019;110:2734-47. doi: 10.1111/cas.14125. PubMed PMID: 31278886; PubMed Central PMCID: PMC6726693.
  14. Sun W, Guo H, Cai M, Ma G, Zhang L, Yu Y, et al. Uridine-cytidine kinase 2 as a novel potential prognostic and therapeutic biomarker in gastric cancer. Transl Cancer Res. 2025;14:8070-85. doi: 10.21037/tcr-2025-1165. PubMed PMID: 41378002; PubMed Central PMCID: PMC12686192.
  15. Wu X, Chen D, Li M, Liang G, Ye H. UCK2 promotes intrahepatic cholangiocarcinoma progression and desensitizes cisplatin treatment by PI3K/AKT/mTOR/autophagic axis. Cell Death Discov. 2024;10:375. doi: 10.1038/s41420-024-02140-x. PubMed PMID: 39179560; PubMed Central PMCID: PMC11344076.
  16. Zhou X, Guo CJ, Chang CC, Zhong J, Hu HH, Lu GM, et al. Structural basis for ligand binding modes of CTP synthase. Proc Natl Acad Sci U S A. 2021;118. doi: 10.1073/pnas.2026621118. PubMed PMID: 34301892; PubMed Central PMCID: PMC8325340.
  17. Lin Y, Zhang J, Li Y, Guo W, Chen L, Chen M, et al. CTPS1 promotes malignant progression of triple-negative breast cancer with transcriptional activation by YBX1. J Transl Med. 2022;20:17. doi: 10.1186/s12967-021-03206-5. PubMed PMID: 34991621; PubMed Central PMCID: PMC8734240.
  18. Durand R, Bellanger C, Kervoelen C, Tessoulin B, Dousset C, Menoret E, et al. Selective pharmacologic targeting of CTPS1 shows single-agent activity and synergizes with BCL2 inhibition in aggressive mantle cell lymphoma. Haematologica. 2024;109:2574-84. doi: 10.3324/haematol.2023.284345. PubMed PMID: 38385294; PubMed Central PMCID: PMC11290505.
  19. Pfeiffer C, Grandits AM, Asnagli H, Schneller A, Huber J, Zojer N, et al. CTPS1 is a novel therapeutic target in multiple myeloma which synergizes with inhibition of CHEK1, ATR or WEE1. Leukemia. 2024;38:181-92. doi: 10.1038/s41375-023-02071-z. PubMed PMID: 37898670.
  20. Heydari N, Mahdizadeh M, Jafari SM. The evolving landscape of involvement of DTYMK enzymes in cancer. Med Oncol. 2023;40:213. doi: 10.1007/s12032-023-02086-7. PubMed PMID: 37358701.
  21. Sun F, Liu Y, Gong T, Pan Q, Xiang T, Zhao J, et al. Inhibition of DTYMK significantly restrains the growth of HCC and increases sensitivity to oxaliplatin. Cell Death Dis. 2021;12:1093. doi: 10.1038/s41419-021-04375-3. PubMed PMID: 34795209; PubMed Central PMCID: PMC8602592.
  22. Zhang L, Chen J, Cheng T, Yang H, Pan C, Li H. Identification of Differentially Expressed Genes and miRNAs Associated with Esophageal Squamous Cell Carcinoma by Integrated Analysis of Microarray Data. Biomed Res Int. 2020;2020:1980921. doi: 10.1155/2020/1980921. PubMed PMID: 32714975; PubMed Central PMCID: PMC7352135.
  23. Ramadan RA, Moghazy TF, Hafez R, Morsi H, Samir M, Shamesya M. Significance of expression of pyrimidine metabolizing genes in colon cancer. Arab J Gastroenterol. 2020;21:189-93. doi: 10.1016/j.ajg.2020.07.006. PubMed PMID: 32830091.
  24. Siddiqui A, Ceppi P. A non-proliferative role of pyrimidine metabolism in cancer. Mol Metab. 2020;35:100962. doi: 10.1016/j.molmet.2020.02.005. PubMed PMID: 32244187; PubMed Central PMCID: PMC7096759.
  25. Zhang L, Tao H, Li J, Zhang E, Liang H, Zhang B. Comprehensive analysis of the competing endogenous circRNA-lncRNA-miRNA-mRNA network and identification of a novel potential biomarker for hepatocellular carcinoma. Aging (Albany NY). 2021;13:15990-6008. doi: 10.18632/aging.203056. PubMed PMID: 34049287; PubMed Central PMCID: PMC8266324.
  26. He G, Qiu J, Liu C, Tian B, Cai D, Liu S. MiR-148b-3p Regulates the Expression of DTYMK to Drive Hepatocellular Carcinoma Cell Proliferation and Metastasis. Front Oncol. 2021;11:625566. doi: 10.3389/fonc.2021.625566. PubMed PMID: 35004265; PubMed Central PMCID: PMC8739515.
  27. Aloliqi AA, Fararjeh AF, Al-Khader A, Kaddumi E, Eisa AA, Jaradat W. The Impact of DTYMK as a Prognostic Marker in Colorectal Cancer. World J Oncol. 2023;14:84-93. doi: 10.14740/wjon1571. PubMed PMID: 36895992; PubMed Central PMCID: PMC9990730.
  28. Zheng J, Wang Q, Yan L, Pan Q, Chen X, Chen Q. The Biological Behavior and Clinical Application Prospects of Deoxythymidine Kinase Gene in Tumors. Technol Cancer Res Treat. 2024;23:15330338241265396. doi: 10.1177/15330338241265396. PubMed PMID: 39420855; PubMed Central PMCID: PMC11497513.
  29. Sun Z, Zhang Z, Wang QQ, Liu JL. Combined Inactivation of CTPS1 and ATR Is Synthetically Lethal to MYC-Overexpressing Cancer Cells. Cancer Res. 2022;82:1013-24. doi: 10.1158/0008-5472.CAN-21-1707. PubMed PMID: 35022212; PubMed Central PMCID: PMC9359733.
  30. Ma S, Pu C. MiR-519e-5p regulates malignant phenotype of breast cancer cells through binding to CTPS1. Exp Cell Res. 2024;442:114225. doi: 10.1016/j.yexcr.2024.114225. PubMed PMID: 39197579.
  31. Asnagli H, Minet N, Pfeiffer C, Hoeben E, Lane R, Laughton D, et al. CTP Synthase 1 Is a Novel Therapeutic Target in Lymphoma. Hemasphere. 2023;7:e864. doi: 10.1097/HS9.0000000000000864. PubMed PMID: 37008165; PubMed Central PMCID: PMC10060080.
  32. Shen G, He P, Mao Y, Li P, Luh F, Ding G, et al. Overexpression of Uridine-Cytidine Kinase 2 Correlates with Breast Cancer Progression and Poor Prognosis. J Breast Cancer. 2017;20:132-41. doi: 10.4048/jbc.2017.20.2.132. PubMed PMID: 28690649; PubMed Central PMCID: PMC5500396.
  33. Huang S, Li J, Tam NL, Sun C, Hou Y, Hughes B, et al. Uridine-cytidine kinase 2 upregulation predicts poor prognosis of hepatocellular carcinoma and is associated with cancer aggressiveness. Mol Carcinog. 2019;58:603-15. doi: 10.1002/mc.22954. PubMed PMID: 30556610.
  34. El Hassouni B, Infante J, Mantini G, Ricci C, Funel N, Giovannetti E, et al. Uridine Cytidine Kinase 2 as a Potential Biomarker for Treatment with RX-3117 in Pancreatic Cancer. Anticancer Res. 2019;39:3609-14. doi: 10.21873/anticanres.13508. PubMed PMID: 31262886.
  35. Zhou L, Zhao C, Li J, Zhang D, Lu B, Chen Z, et al. Relationship between up-regulation of DTYMK expression and immune infiltration for the prognosis of lung adenocarcinoma. J Clin Lab Anal. 2022;36:e24234. doi: 10.1002/jcla.24234.
  36. Zhou Q, Jiang H, Zhang J, Yu W, Zhou Z, Huang P, et al. Uridine-cytidine kinase 2 promotes metastasis of hepatocellular carcinoma cells via the Stat3 pathway. Cancer Manag Res. 2018;10:6339-55. doi: 10.2147/CMAR.S182859. PubMed PMID: 30568496; PubMed Central PMCID: PMC6267774.
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