The comparison of telomere length in cancer patients: Plasma, whole blood and tumor tissue
The comparison of telomere length in cancer patients: Plasma, whole blood and tumor tissue
Telomer dysfunction triggers numerical and structural chromosomal instability and initiates tumorigenesis. Classical biopsies provide information about parts of tumor tissue, but cancer is divided into subgroups according to its mutational and behavioral characteristics. In this study, we aimed to investigate whether the results of cellfree-DNA were compatible with those obtained from tissues and to investigate whether cellfree-DNA telomere length is an alternative non-invasive method for the diagnosis of cancer. This study included the Q-PCR telomere measurement of tumor tissue, peripheral blood and plasma samples in patients with various cancers and peripheral blood and plasma samples of a control group. The telomeric DNA length and T/S ratios were calculated using the T/S ratio (2-ΔΔCt) formula. The median value for the plasma relative T/S ratio of the cancer group was statistically significantly higher than control group. In the cancer group, the lowest relative T/S ratio was found in plasma samples. The mean T/S ratio of whole blood was higher than tumor tissue, and similarly the relative T/S ratio of tumor tissue was higher than plasma T/S ratio( whole blood>tumor tissue>cfDNA). In cancer patients, the longer telomere length suggests that plasma cellfree-DNA telomere length could be a new molecular marker in cancer diagnosis and follow-up.
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- 1. Hande MP. Orchestration of telomeres and DNA repair factors in mammalian cells. in: DNA repair and human disease. Springer; 2006. p. 114–27.
- 2. Martínez P, Blasco MA. Telomeric and extra-telomeric roles for telomerase and the telomere-binding proteins. Nat Rev Cancer [Internet]. 2011;11:161– 76. Available from: http://libproxy.smith.edu:2048/login?url=http://search. ebscohost.com/login.aspx?direct=true&db=aph&AN=58638220&site=e ds-live.
- 3. Jeggo PA, Pearl LH, Carr AM. DNA repair, genome stability and cancer: A historical perspective. Nat Rev Cancer [Internet]. 2016;16:35–42. Available from: http://dx.doi.org/10.1038/nrc.2015.4.
- 4. Deng Y, Chan SS, Chang S. Telomere dysfunction and tumour suppression: The senescence connection. Nat Rev Cancer [Internet]. 2008;8:450–8. Available from: http://www.nature.com/doifinder/10.1038/ nrc2393%5Cnhttp://www.ncbi.nlm.nih.gov/pubmed/18500246%5Cnhttp:// www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC3688269.
- 5. Bertorelle R, Rampazzo E, Pucciarelli S, et al. Telomeres, telomerase and colorectal cancer. World J Gastroenterol. 2014;20:1940–50.
- 6. Yoon JH, Seo HS, Choi WS, et al. Gastrokine 1 induces senescence and apoptosis through regulating telomere length in gastric cancer. Oncotarget. 2014;5:11695.
- 7. Duggan C, Risques R, Alfano C, et al. Change in peripheral blood leukocyte telomere length and mortality in breast cancer survivors. J Natl Cancer Inst. 2014;106:dju035.
- 8. Janku F, Vibat CRT, Kosco K, et al. BRAF V600E mutations in urine and plasma cell-free DNA from patients with Erdheim-Chester disease. Oncotarget. 2014;5:3607.
- 9. Fleischhacker M, Schmidt B. Circulating nucleic acids (CNAs) and cancer—a survey. Biochim Biophys Acta (BBA)-Reviews Cancer. 2007;1775:181–232.
- 10. De Mattos-Arruda L, Olmos D, Tabernero J. Prognostic and predictive roles for circulating biomarkers in gastrointestinal cancer. Futur Oncol. 2011;7:1385–97.
- 11. Crowley E, Di Nicolantonio F, Loupakis F, et al. Liquid biopsy: Monitoring cancer-genetics in the blood. Nat Rev Clin Oncol [Internet]. 2013;10:472– 84. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23836314.
- 12. Rosenthal R, McGranahan N, Herrero J, et al. Deciphering genetic intratumor heterogeneity and its impact on cancer evolution. Annu Rev Cancer Biol. 2017.1:223-2.
- 13. Murtaza M, Dawson S-J, Pogrebniak K, et al. Multifocal clonal evolution characterized using circulating tumour DNA in a case of metastatic breast cancer. Nat Commun. 2015;6.
- 14. Cawthon RM. Telomere measurement by quantitative PCR. Nucleic Acids Res [Internet]. 2002;30:e47. Available from: http://www.ncbi.nlm.nih.gov/ pubmed/19129229.
- 15. Kim J-H, Kim HK, Ko J-H, et al. The relationship between leukocyte mitochondrial DNA copy number and telomere length in communitydwelling elderly women. PLoS One [Internet]. 2013;8:e67227. Available from: http://dx.plos.org/10.1371/journal.pone.0067227.
- 16. Wan JCM, Massie C, Garcia-corbacho J, et al. Liquid biopsies come of age: Clinical applications of circulating tumour DNA. Nat Rev Cancer [Internet]. 2016;1–16. Available from: http://dx.doi.org/10.1038/nrc.2017.7.
- 17. Fu X, Wan S, Hann H-W, et al. Relative telomere length: A novel noninvasive biomarker for the risk of non-cirrhotic hepatocellular carcinoma in patients with chronic hepatitis B infection. Eur J Cancer [Internet]. 2012;48:1014–22. Available from: http://www.pubmedcentral.nih.gov/ articlerender.fcgi?artid=3324593&tool=pmcentrez&rendertype=abstract.
- 18. Gormally E, Caboux E, Vineis P, et al. Circulating free DNA in plasma or serum as biomarker of carcinogenesis: Practical aspects and biological significance. Mutat Res Mutat Res. 2007;635:105–17.
- 19. Jung K, Fleischhacker M, Rabien A. Cell-free DNA in the blood as a solid tumor biomarker—a critical appraisal of the literature. Clin Chim Acta. 2010;411:1611–24.
- 20. Wan S, Hann H-W, Myers RE, et al. Telomere length in circulating serum DNA as a novel non-invasive biomarker for cirrhosis: a nested case-control analysis. Liver Int Off J Int Assoc Study Liver. 2012;32:1233–41.
- 21. Shi Y, Zhang Y, Zhang L, et al. Telomere length of circulating cell-free DNA and gastric cancer in a chinese population at high-risk. Front Oncol [Internet]. 2019 17;9:1434. Available from: https://pubmed.ncbi.nlm.nih. gov/31921685.
- 22. Wu X, Tanaka H, Wu X, et al. Aberrant reduction of telomere repetitive sequences in plasma cell-free DNA for early breast cancer detection. Oncotarget [Internet]. 2015;6:29795–807. Available from: http://www. oncotarget.com/abstract/5083.
- 23. Chen Y, Qu F, He X, et al. Short leukocyte telomere length predicts poor prognosis and indicates altered immune functions in colorectal cancer patients. Ann Oncol. 2014;25:869–76.
- 24. Gramatges MM, Telli ML, Balise R, et al. Longer relative telomere length in blood from women with sporadic and familial breast cancer compared with healthy controls. Cancer Epidemiol Biomarkers Prev. 2010;19:605–13.
- 25. Liu J, Yang Y, Zhang H, et al. Longer leukocyte telomere length predicts increased risk of hepatitis b virus-related hepatocellular carcinoma: A casecontrol analysis. Cancer. 2011;117:4247–56.
- 26. Hastie ND, Dempster M, Dunlop MG, et al. Telomere reduction in human colorectal carcinoma and with ageing. Nature. 1990;346:866.
- 27. Engelhardt M, Drullinsky P, Guillem J, et al. Telomerase and telomere length in the development and progression of premalignant lesions to colorectal cancer. Clin cancer Res. 1997;3:1931–41.
- 28. Gertler R, Rosenberg R, Stricker D, et al. Prognostic potential of the telomerase subunit human telomerase reverse transcriptase in tumor tissue and nontumorous mucosa from patients with colorectal carcinoma. Cancer. 2002;95:2103–11.
- 29. Valls‐Bautista C, Piñol‐Felis C, Reñé‐Espinet JM, et al. In colon cancer, normal colon tissue and blood cells have altered telomere lengths. J Surg Oncol. 2015;111:899–904.
- 30. Zinkova A, Brynychova I, Svacina A, et alM. Cell-free DNA from human plasma and serum differs in content of telomeric sequences and its ability to promote immune response. Sci Rep [Internet]. 2017 Jun 1;7:2591. Available from: https://pubmed.ncbi.nlm.nih.gov/28572683.