Author(s):
Mubarak R., Soukkarieh Ch., Al-fahoum S.
Email(s):
roushanmub110@gmail.com
DOI:
10.52711/0974-360X.2025.00711 
Address:
Mubarak R.1*., Soukkarieh Ch. 2, Al-fahoum S.1
1Department of Biochemistry and Microbiology, Faculty of Pharmacy, Damascus University.
2Department of Animal Biology, Faculty of Science, Damascus University.
*Corresponding Author
Published In:
Volume - 18,
Issue - 10,
Year - 2025
ABSTRACT:
Breast cancer is one of the most common malignancies in the world, high incidence of mortality in low and medium income countries may be caused by a delay in the detection of tumors especially in Syria due to crisis and sever sanctuary. Telomeres are repeated DNA sequences are added onto chromosomal ends by telomerase, an enzyme with a reverse transcriptase activity, it consists mainly of two subunits a telomerase reverse transcriptase (hTERT), a telomerase RNA component (TERC) The aim of our study was to find out whether there is a detectable levels of hTERT mRNA in plasma of newly diagnosed breast cancer Syrian patients. (64) informed and consented female patients mean age(48.8), newly diagnosed with breast cancer and before any treatment and (18) normal females mean age (47.5) as healthy control were included, hTERT mRNA in plasma samples were assayed using q RT PCR. The presence of plasma hTERT mRNA was detected in 33/64 samples (51.5%), plasma hTERT mRNA was not found in samples from all healthy subjects (100%). We found a statistically significant difference between the breast cancer patients and healthy subjects (p= 0.001) plasma hTERT mRNA was related to tumor size (P =0.0001), tumor grade (P=0.003) and the presence of nodal metastases (P =0.042), but not related to patient age (P =0.99), receptors status :PR (p =0.58), ER (0.99), HER2 (p=0.37), or tumor type (p= 0.61) We concluded that circulating cell-free hTERT mRNA might be potential and beneficial non-invasive tumor marker for breast cancer that must be further analysed and need studies focusing on HTERT protein level and telomerase enzymatic activity.
Cite this article:
Mubarak R., Soukkarieh Ch., Al-fahoum S.. Telomerase Reverse Transcriptase mRNA as a detection marker in the Plasma of Syrian Breast Cancer patients. Research Journal of Pharmacy and Technology. 2025;18(10):4929-3. doi: 10.52711/0974-360X.2025.00711
Cite(Electronic):
Mubarak R., Soukkarieh Ch., Al-fahoum S.. Telomerase Reverse Transcriptase mRNA as a detection marker in the Plasma of Syrian Breast Cancer patients. Research Journal of Pharmacy and Technology. 2025;18(10):4929-3. doi: 10.52711/0974-360X.2025.00711 Available on: https://rjptonline.org/AbstractView.aspx?PID=2025-18-10-50
REFERENCES:
1. GBD 2019 Cancer Risk Factors Collaborators. The global burden of cancer attributable to risk factors, 2010-19: a systematic analysis for the Global Burden of Disease Study 2019. Lancet. 2022; Aug 20; 400(10352): 563-591. doi: 10.1016/S0140-6736(22)01438-6. PMID: 35988567; PMCID: PMC9395583.
2. https://gco.iarc.who.int/media/globocan/factsheets/cancers/20-breast-fact-sheet.pdf
3. https://www.who.int/news-room/fact-sheets/detail/breast-cancer
4. Sampoornam. W. Stress and Quality of Life among Breast Cancer Patients. Asian J. Nur. Edu. & Research. 2014; 4(3): 325-327.
5. Arti Tiwari, Maharaj Singh, Bharati Sahu. Risk Factors for Breast Cancer. International Journal of Nursing Education and Research. 2022; 10(3):276-2. doi: 10.52711/2454-2660.2022.00065
6. Wang L. Early Diagnosis of Breast Cancer. Sensors. 2017; 17(7):1572. https://doi.org/10.3390/s17071572
7. V. N. Dange, S. J. Shid, C.S. Magdum, S.K. Mohite. A Review on Breast cancer: An Overview. Asian J. Pharm. Res. 2017; 7(1): 49-51. doi: 10.5958/2231-5691.2017.00008.9
8. Milosevic M, Jankovic D, Milenkovic A, Stojanov D. Early diagnosis and detection of breast cancer. Technol Health Care. 2018; 26(4): 729-759. doi: 10.3233/THC-181277.
9. Arti Tiwari, Maharaj Singh, Bharati Sahu. Risk Factors for Breast Cancer. International Journal of Nursing Education and Research. 2022; 10(3): 276-2. doi: 10.52711/2454-2660.2022.00065
10. 200M. Geetha, K. Menaka, P. Padmavathi. Awareness of Breast self-examination and risk factors of Breast Cancer among Women. Asian J. Nur. Edu. and Research. 2017; 7(3): 413-416. doi: 10.5958/2349-2996.2017.00082.9
11. Iacob, R. et al. Evaluating the Role of Breast Ultrasound in Early Detection of Breast Cancer in Low- and Middle-Income Countries: A Comprehensive Narrative Review. Bioengineering. 2024, 11, 262. https://doi.org/10.3390/
12. Sampoornam W. Nurse Researcher’s Role in Breast Cancer Biomarkers. Int. J. Adv. Nur. Management. 2014; 2(1): 46-47
13. Vimlendu Bhushan Sinha, Neha Pandey, Pankaj Taneja. Biomarker Genes for Gynaecological Cancers. Research J. Pharm. and Tech. 2016; 9(10): 1641-1646. doi: 10.5958/0974-360X.2016.00329.2
14. V. Jayashree, Malarkodi Velraj. Breast Cancer and various Prognostic Biomarkers for the diagnosis of the disease: A Review. Research J. Pharm. and Tech. 2017; 10(9): 3211-3216. doi: 10.5958/0974-360X.2017.00570.4
15. de Lange T. Activation of telomerase in a human tumor. Proc Natl Acad Sci USA. 1994; Apr 12;91(8): 2882-5. doi: 10.1073/pnas.91.8.2882.
16. Amano H, et al.Telomere dysfunction induces sirtuin repression that drives telomeredependent disease. Cell Metab. 2019; 29: 1274–90.e9.
17. Srinivas N, Rachakonda S, Kumar R. Telomeres and telomere length: a general overview. Cancers (Basel). 2020;12:558.
18. Amir M.et al. Structural features of nucleoprotein CST/shelterin complex involved in the telomere maintenance and its association with disease mutations. Cells. 2020;9:359
19. Greider CW, Blackburn EH. Identification of a specific telomere terminal transferase activity in Tetrahymena extracts. Cell. 1985; 43(2 Pt 1): 405–13.
20. Greider CW, Blackburn EH. The telomere terminal transferase of Tetrahymena is a ribonucleoprotein enzyme with two kinds of primer specificity. Cell. 1987; 51(6): 887–98.
21. Weinrich SL, Pruzan R, Ma L, Ouellette M, Tesmer VM, Holt SE, et al. Reconstitution of human telomerase with the template RNA component hTR and the catalytic protein subunit hTRT. Nat Genet. 1997; 17(4): 498–502.
22. de Lange T. How telomeres solve the end-protection problem. Science (New York, NY). 2009; 326(5955): 948–52
23. Colebatch, A. J., Dobrovic, A., and Cooper,W. A. (2019). TERT gene: its function and dysregulation in cancer. J. Clin. Pathol. 72, 281–284. doi:10.1136/jclinpath- 2018-205653
24. Akshay R. Yadav, Shrinivas K. Mohite. Cancer- A Silent Killer: An Overview. Asian J. Pharm. Res. 2020; 10(3): 213-216. doi: 10.5958/2231-5691.2020.00036.2
25. Harsh Vardhan Singh, Mo. Shahid, Ashish Jain, Akhlesh Kumar Singhai. Breast Cancer: From Etiology to Therapeutic Interventions. Research Journal of Pharmacology and Pharmacodynamics. 2024; 16(3): 199-7. doi: 10.52711/2321-5836.2024.00034
26. Gong, C., Yang,H., Wang, S., Liu, J., Li, Z., Hu, Y., et al. (2021). hTERT promotes CRC proliferation and migration by recruiting YBX1 to increase NRF2 expression. Front. Cell Dev. Biol. 9, 658101. doi:10.3389/fcell.2021.658101
27. Kwon, J. H., and Yi, J. W. Correlation between telomerase reverse transcriptase messenger RNA expression and survival of patients with papillary thyroid carcinoma. Surgery. 2021; 169: 43–49. doi:10.1016/j.surg.2020.04.054
28. Li, S. et al. TERT promoter methylation is associated with high expression of TERT and poor prognosis in papillary thyroid cancer. Front. Oncol. 2024; 14: 1325345. doi:10.3389/fonc.2024.1325345
29. Gupta S, et al.TERT copy number alterations, promoter mutations and rearrangements in adrenocortical carcinomas. Endocr Pathol. 2022; 33: 304–14.
30. Meyerson M: Role of telomerase in normal and cancer cells. J Clin Oncol 2000; 18(13): 2626–2634.
31. O'Sullivan RJ, Karlseder J: Telomeres: protecting chromosomes against genome instability. Nat Rev Mol Cell Biol. 2010; 11(3): 171–181.
32. Hanahan D, Weinberg RA: The hallmarks of cancer. Cell. 2000; 100(1): 57–70.
33. Wang L et al. Association of a functional tandem repeats in the downstream of human telomerase gene and lung cancer. Oncogene 2003; 22(46): 7123–7129.
34. Andersson U et al .MNS16A minisatellite genotypes in relation to risk of glioma and meningioma and to glioblastoma outcome. Int J Cancer. 2009; 125(4): 968–972
35. Wang Y et al. A tandem repeat of human telomerase reverse transcriptase (hTERT) and risk of breast cancer development and metastasis in Chinese women. Carcinogenesis. 2008, 29(6): 1197–1201.
36. Zagouri F.et al HTERT MNS16A polymorphism in breast cancer: a case-control study. Mol Biol Rep. 2012; 39(12): 10859–10863
37. Wu H. et al. Association between the Telomerase Reverse Transcriptase (TERT) rs2736098 Polymorphism and Cancer Risk: Evidence from a Case-Control Study of Non-Small-Cell Lung Cancer and a Meta-Analysis. PLoS ONE. 2013; 8(11): e76372. doi:10.1371/ journal.pone.007637
38. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods; 2001: 25(4): 402–408. https :// doi.org/10.1006/meth.2001.1262
39. Hiyama, E.et al . Telomerase activity in human breast tumors. J. Natl. Cancer Inst. 1996., 88: 116– 122
40. Bednarek, A. K.et al. Analysis of telomerase activity levels in breast cancer: positive detection at the in situ breast carcinoma stage. Clin. Cancer Res. 1997; 3: 11–16
41. Roos, G.et al. Telomerase activity in relation to p53 status and clinicopathological parameters in breast cancer. Int. J. Cancer, 1998; 79: 343–348
42. Clark, G. M., Osborne, C. K., Levitt, D., Wu, F., and Kim, N. W. Telomerase activity and survival of patients with node-positive breast cancer. J. Natl. Cancer Inst. 1997; 89: 1874–1880
43. Carey, L. et al. Careful histological confirmation and microdissection reveal telomerase activity in otherwise telomerase- negative breast cancers. Clin. Cancer Res. 1998; 4: 435–440,
44. Tsao, J. I.et al. . Telomerase activity in normal and neoplastic breast. Clin. Cancer Res. 1997; 3: 627–631
45. Hahn, W. C.et al. Creation of human tumour cells with defined genetic elements. Nature. 1999; 400: 464–468
46. Yang R et al. Regulation and clinical potential of telomerase reverse transcriptase (TERT/ hTERT) in breast cancer Cell Commun Signal. 2023 Aug 23; 21(1): 218. doi: 10.1186/s12964-023-01244-8.
47. Xu qi Chen et al. Telomerase RNA as a Detection Marker in the Serum of Breast Cancer Patients. Clin Cancer Res. 2000; Oct; 6(10): 3823-6. PMID: 11051224.
48. Kang et al. Circulating cell-free human telomerase reverse transcriptase mRNA in plasma and its potential diagnostic and prognostic value for gastric cancer. Int J Clin Oncol. 2013 Jun; 18(3): 478-86. doi: 10.1007/s10147-012-0405-9.
49. Perhavec A, Cerkovnik P, Novakovic S, Zgajnar J. The hTERT mRNA in plasma samples of early breast cancer patients, non-cancer patients and healthy individuals. Neoplasma. 2008; 55(6): 549-54. PMID: 18999886.
50. Jeong YJ, Park SH, Jeon CH. Detection of circulating tumor cells in patients with breast cancer using the conditionally reprogrammed cell culture method and reverse transcription-PCR hTERT and MAGE A1-6. Oncol Lett. 2020; Oct; 20(4): 78. doi: 10.3892/ol.2020.11939.