Document Type : Original Research
Authors
- Fahad Mansoor Samadi 1
- Shaista Suhail 1
- Manjari Sonam 2
- Mohd Kaleem Ahmad 3
- Vijay Kumar 4
- Shaleen Chandra 1
- Shadab Mohammad 5
1 Department of Oral Pathology and Microbiology, King George Medical University, Lucknow, India
2 Department of Oral Pathology and Microbiology, Sardar Patel PG Institute of Dental and Medical Sciences, Lucknow, India
3 Department of Biochemistry, KGMU, Lucknow, India
4 Department of Surgical Oncology, King George Medical University, Lucknow, India
5 Department of Oral Maxillofacial Surgery, King George Medical University, Lucknow, India
Abstract
Background & Objective: Telomeres consist of repetitive G-rich nucleotides located at the end of each chromosome, acting as protein binding sites. The aim of this study was to examine the differences in telomere length in blood, saliva, and tissue samples at various stages of oral precancerous and cancerous lesions.
Methods: Samples of blood, tissue, and saliva were collected from patients with oral precancerous and cancerous lesions. DNA extraction was performed. Then, a TRAP assay was conducted to assess and compare the telomere length and telomerase expression.
Results: The levels of telomerase activity (TA) in the DNA samples ranged from 0.19 to 6.91 (2.05+1.37) among oral squamous cell carcinoma (OSCC) patients and from 0.17 to 4.5 (0.28+4.25) among precancerous patients. A significant difference was observed in TA levels between OSCC and precancerous samples (t=3.9691, P= 0.0000).
Conclusion: Assessing the telomerase activity is crucial for studying the behavior of carcinoma in the clinical setting. The augmented telomerase expression and the length of telomere contribute to OSCC progression. Hence, this study adds a diagnostic tool that can serve as a biomarker for the early detection and prognosis of OSCC.
Keywords
Main Subjects
- Artandi SE, DePinho RA. Telomeres and telomerase in cancer. Carcinogenesis. 2010;31(1):9-18. [DOI:10.1093/carcin/bgp268] [PMID]
- Van Steensel B, Smogorzewska A, De Lange T. TRF2 protects human telomeres from end-to-end fusions. Cell. 1998;92(3):401-13. [DOI:10.1016/S0092-8674(00)80932-0] [PMID]
- Karlseder J, Broccoli D, Dai Y, Hardy S, de Lange T. p53-and ATM-dependent apoptosis induced by telomeres lacking TRF2. Science. 1999;283(5406):1321-5. [DOI:10.1126/science.283.5406.1321] [PMID]
- Sandell LL, Zakian VA. Loss of a yeast telomere: arrest, recovery, and chromosome loss. Cell. 1993;75(4):729-39. [DOI:10.1016/0092-8674(93)90493-A] [PMID]
- Deng Y, Chan SS, Chang S. Telomere dysfunction and tumour suppression: the senescence connection. Nat Rev Cancer. 2008;8(6):450-8. [DOI:10.1038/nrc2393] [PMID]
- Ohtani N, Mann DJ, Hara E. Cellular senescence: its role in tumor suppression and aging. Cancer Sci. 2009;100(5):792-7. [DOI:10.1111/j.1349-7006.2009.01123.x] [PMID]
- von Zglinicki T, Saretzki G, Döcke W, Lotze C. Mild hyperoxia shortens telomeres and inhibits proliferation of fibroblasts: a model for senescence?. Exp Cell Res. 1995;220(1):186-93. [DOI:10.1006/excr.1995.1305] [PMID]
- Alnafakh RA, Adishesh M, Button L, Saretzki G, Hapangama DK. Telomerase and telomeres in endometrial cancer. Front Oncol. 2019;9:344. [DOI:10.3389/fonc.2019.00344] [PMID]
- Bau DT, Lippman SM, Xu E, Gong Y, Lee JJ, Wu X, Gu J. Short telomere lengths in peripheral blood leukocytes are associated with an increased risk of oral premalignant lesion and oral squamous cell carcinoma. Cancer. 2013;119(24):4277-83. [DOI:10.1002/cncr.28367] [PMID]
- Harley CB, Futcher AB, Greider CW. Telomeres shorten during ageing of human fibroblasts. Nature. 1990;345(6274):458-60. [DOI:10.1038/345458a0] [PMID]
- Oeseburg H, de Boer RA, Van Gilst WH, van der Harst P. Telomere biology in healthy aging and disease. Pflug Arch Eur J Physiol. 2010;459:259-68. [DOI:10.1007/s00424-009-0728-1] [PMID]
- Watson JM, Riha K. Telomeres, aging, and plants: from weeds to Methuselah–a mini-review. Gerontology. 2011;57(2):129-36. [DOI:10.1159/000310174] [PMID]
- Chan SR, Blackburn EH. Telomeres and telomerase. Philosophical Transactions of the Royal Society of London. Series B: Biol Sci. 2004;359(1441):109-22. [DOI:10.1098/rstb.2003.1370] [PMID]
- Barczak W, Rozwadowska N, Romaniuk A, Lipińska N, Lisiak N, Grodecka‑Gazdecka S, Książek K, Rubiś B. Telomere length assessment in leukocytes presents potential diagnostic value in patients with breast cancer. Oncol Lett. 2016;11(3):2305-9. [DOI:10.3892/ol.2016.4188] [PMID]
- Garcia SB, Park HS, Novelli M, Wright NA. Field cancerization, clonality, and epithelial stem cells: the spread of mutated clones in epithelial sheets. J Pathol. 1999;187(1):61-81. [DOI:10.1002/(SICI)1096-9896(199901)187:13.0.CO;2-I]
- LIND PO. Malignant transformation in oral leukoplakia. Eur J Oral Sci. 1987;95(6):449-55. [DOI:10.1111/j.1600-0722.1987.tb01959.x] [PMID]
- Yang H, Lippman SM, Huang M, Lee JJ, Wang W, Spitz MR, Wu X. Genetic polymorphisms in double-strand break DNA repair genes associated with risk of oral premalignant lesions. Eur J Cancer. 2008;44(11):1603-11. [DOI:10.1016/j.ejca.2008.05.006] [PMID] []
- Wang Y, Spitz MR, Lee JJ, Huang M, Lippman SM, Wu X. Nucleotide excision repair pathway genes and oral premalignant lesions. Clin Cancer Res. 2007;13(12):3753-8. [DOI:10.1158/1078-0432.CCR-06-1911] [PMID]
- Tsantoulis PK, Kastrinakis NG, Tourvas AD, Laskaris G, Gorgoulis VG. Advances in the biology of oral cancer. Oral Oncol. 2007;43(6):523-34. [DOI:10.1016/j.oraloncology.2006.11.010] [PMID]
- Samadi FM, Suhail S, Sonam M, Ahmad MK, Chandra S, Saleem M. Telomerase in saliva: An assistant marker for oral squamous cell carcinoma. Journal of oral and maxillofacial pathology: JOMFP. 2019;23(2):187. [DOI:10.4103/jomfp.JOMFP_83_19] [PMID]
- Shen J, Gammon MD, Terry MB, Bradshaw PT, Wang Q, Teitelbaum SL, Neugut AI, Santella RM. Genetic polymorphisms in telomere pathway genes, telomere length, and breast cancer survival. Breast Cancer Res Treat. 2012;134:393-400. [DOI:10.1007/s10549-012-2058-9] [PMID]
- Wells GA, Shea B, O’Connell D, Peterson J, Welch V, Losos M, et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. 3rd Symposium on Systematic Reviews: Beyond the Basics; 2000 Jul 3-5; Oxford, UK.
- Zhang DH, Chen JY, Hong CQ, Yi DQ, Wang F, Cui W. High‐risk human papillomavirus infection associated with telomere elongation in patients with esophageal squamous cell carcinoma with poor prognosis. Cancer. 2014;120(17):2673-83. [DOI:10.1002/cncr.28797] [PMID]
- Kim NW, Piatyszek MA, Prowse KR, Harley CB, West MD, Ho PL, Coviello GM, Wright WE, Weinrich SL, Shay JW. Specific association of human telomerase activity with immortal cells and cancer. Science. 1994;266(5193):2011-5. [DOI:10.1126/science.7605428] [PMID]
- Tahara H, Kuniyasu H, Yokozaki H, Yasui W, Shay JW, Ide T, Tahara E. Telomerase activity in preneoplastic and neoplastic gastric and colorectal lesions. Clin Cancer Res. 1995;1(11):1245-51.
- De Lange T. How telomeres solve the end-protection problem. Science. 2009;326(5955):948-52. [DOI:10.1126/science.1170633] [PMID]
- Zhang C, Chen X, Li L, Zhou Y, Wang C, Hou S. The association between telomere length and cancer prognosis: evidence from a meta-analysis. PloS One. 2015;10(7):e0133174. [DOI:10.1371/journal.pone.0133174] [PMID]
- Huang YK, Fan XG, Qiu F, Wang ZM. Combined detection of mRNA expression of Alpha-fetoprotein in peripheral blood and telomerase activity of monocytes in hepatocellular carcinoma patients. Hepato Gastro. 2013;60(121):1-5. [DOI:10.5754/hge12359]
- Lu L, Zhang C, Zhu G, Irwin M, Risch H, Menato G, Mitidieri M, Katsaros D, Yu H. Telomerase expression and telomere length in breast cancer and their associations with adjuvant treatment and disease outcome. Breast Cancer Res. 2011;13(3):1-8. [DOI:10.1186/bcr2893] [PMID]
- Lan Q, Cawthon R, Gao Y, Hu W, Hosgood III HD, Barone-Adesi F, Ji BT, Bassig B, Chow WH, Shu X, Cai Q. Longer telomere length in peripheral white blood cells is associated with risk of lung cancer and the rs2736100 (CLPTM1L-TERT) polymorphism in a prospective cohort study among women in China. PloS One. 2013;8(3):e59230. [DOI:10.1371/journal.pone.0059230] [PMID]
- Qin Q, Sun J, Yin J, Liu L, Chen J, Zhang Y, Li T, Shi Y, Wei S, Nie S. Telomere length in peripheral blood leukocytes is associated with risk of colorectal cancer in Chinese population. PloS One. 2014;9(2):e88135. [DOI:10.1371/journal.pone.0088135] [PMID]
- Maruyama Y, Hanai H, Kaneko E. Telomere length and telomerase activity in intestinal metaplasia, adenoma and well differentiated adenocarcinoma of the stomach. Nihon rinsho. JPN J Clin Med. 1998;56(5):1186-9. PMID: 9613119
- Sainger RN, Telang SD, Shukla SN, Patel PS. Clinical significance of telomere length and associated proteins in oral cancer. Biomark Insights. 2007;2:117727190700200030. [DOI:10.1177/117727190700200030] [PMID]
- Zhu X, Han W, Xue W, Zou Y, Xie C, Du J, Jin G. The association between telomere length and cancer risk in population studies. Sci Rep 2016;6(1):22243. [DOI:10.1038/srep22243] [PMID]
- Rai A, Naikmasur VG, Sattur A. Quantification of telomerase activity in normal oral mucosal tissue and oral squamous cell carcinoma. Int J Med Paediatr Oncol. 2016;37(03):183-8. [DOI:10.4103/0971-5851.190350] [PMID]
- Pal J, Rajput Y, Shrivastava S, Gahine R, Mungutwar V, Barardiya T, Chandrakar A, Ramakrishna PP, Mishra SS, Banjara H, Choudhary V. A standalone approach to utilize telomere length measurement as a surveillance tool in oral leukoplakia. Mol Oncol. 2022;16(8):1650-60. [DOI:10.1002/1878-0261.13133] [PMID]
- Pannone G, De Maria S, Zamparese R, Metafora S, Serpico R, Morelli F, Rubini C, Farina E, Carteni M, Staibano S, De Rosa G. Prognostic value of human telomerase reverse transcriptase gene expression in oral carcinogenesis. Int J Oncol. 2007;30(6):1349-57. [DOI:10.3892/ijo.30.6.1349] [PMID]
- Liao J, Mitsuyasu T, Yamane K, Ohishi M. Telomerase activity in oral and maxillofacial tumors. Oral Oncol. 2000;36(4):347-52. [DOI:10.1016/S1368-8375(00)00013-0] [PMID]
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