Clinical and prognostic value of hTERT mRNA expression in patients with non-small-cell lung cancer.
AbstractTelomerase, undetectable in normal somatic cells, plays a critical role in carcinogenesis of the majority of human tumors including lung carcinoma. The aim of our study was to determine human telomerase reverse transcriptase (hTERT) mRNA expression in patients with non-small cell lung cancer (NSCLC) in order to estimate its usefulness as diagnostic and/or prognostic factor. hTERT expression were analyzed in a group of 12 females and 28 males with NSCLC using Quantitative Real-Time Polymerase Chain Reaction – the QRT-PCR method in cancerous and non-cancerous lung tissues. Results were analyzed according to clinical data and one-, two-, and five-year survival rates. hTERT expression in the cancerous tissue was significantly higher than in the lung parenchyma free from neoplasm infiltration (p<0.05). There was no significant association between hTERT expression in the tumor tissue and age, gender, histological type of the tumor, grading or clinical stage. A significant difference in hTERT expression between two types of histopathological pattern (adenocarcinoma and squamous cell carcinoma) was detected (p=0.01). No association between hTERT expression in NSCLC specimens and survival rates was found. hTERT mRNA detection by QRT-PCR in tumor and corresponding cancer-free tissues can be used as a diagnostic marker in patients with NSCLC, but seems not to be a prognostic factor.
Albanell J, Lonardo F, Rusch V, Engelhardt M, Langenfeld J, Han W, Klimstra D, Venkatraman E, Moore MA, Dmitrovsky E (1997) High telomerase activity in primary lung cancers: association with increased cell proliferation rates and advanced pathologic stage. J Natl Cancer Inst 89: 1609-1615.
Armanios M, Blackburn EH (2012) The telomere syndromes. Nat Rev Genet 13: 693-704. doi: 10.1038/nrg3246.
Chen C-H, Chen R-J (2011) Prevalence of telomerase activity in human cancer. J Farmos Med Assoc 110: 275-289.
Dobija-Kubica K, Zalewska-Ziob M, Bruliński K, Rogoziński P, Wiczkowski A, Gawrychowska A, Gawrychowski J (2016) Telomerase activity in non-small cell lung cancer. Pol J Thorac Cardiovasc Surg 13:15-20.
Driscoll B, Buckley S, Chi Bui K, Anderson KD, Warburton D (2000) Telomerase in alveolar epithelial development and repair. Am J Physiol Lung Cell Mol Physiol 279: L1191–L1198.
Ettinger DS, Akerley W, Bepler G, Blum MG, Chang A, Cheney RT, Chirieac LR, D'Amico TA, Demmy TL, Ganti AK, Govindan R, Grannis FW Jr, Jahan T, Jahanzeb M, Johnson DH, Kessinger A, Komaki R, Kong FM, Kris MG, Krug LM, Le QT, Lennes IT, Martins R, O'Malley J, Osarogiagbon RU, Otterson GA, Patel JD, Pisters KM, Reckamp K, Riely GJ, Rohren E, Simon GR, Swanson SJ, Wood DE, Yang SC (2010) Non-small cell lung cancer, version 6.2015. J Natl Compr Cancer Network 8: 740-801.
Fujita Y, Fujikane T, Fujiuchi S, Nishigaki Y, Yamazaki Y, Nagase A, Shimizu T, Ohsaki Y, Kikuchi K (2003) The diagnostic and prognostic relevance of human telomerase reverse transcriptase mRNA expression detected in situ in patients with nonsmall cell lung carcinoma. Cancer 98: 1008-1013.
Goldstraw P, Crowley J, Chansky K, Giroux DJ, Groome PA, Rami-Porta R, Postmus PE, Rusch V (2007) The IASLC Lung Cancer Staging Project: Proposals for the Revision of the TNM Stage Groupings in the Forthcoming (Seventh) Edition of the TNM Classification of Malignant Tumours. J Thorac Oncol 2: 706–714.
Hara H, Yamashita K, Shinada J, Yoshimura H, Kameya T (2001) Clinicopathologic significance of telomerase activity and hTERT mRNA expression in non-small cell lung cancer. Lung Cancer 34: 219-226.
Hashim M, Sayed M, Samy N, Elshazly S (2011) Prognostic significance of telomerase activity and some tumor markers in non-small cell lung cancer. Med Oncol 28: 322-330.
Hiyama E, Hiyama K (2002) Clinical utility of telomerase in cancer. Oncogene 21: 643-649.
Hiyama E, Hiyama K, Yokoyama T, Shay (2001) Immunohistochemical detection of telomerase (hTERT) protein in human cancer tissues and a subset of cells in normal tissues. Neoplasia 3: 17-26.
Jafri M A., Ansari S.A., Alqahtani M.H., Shay J.W (2016) Roles of telomeres and telomerase in cancer, and advances in telomerase-targeted therapies. Genome Med 8: 69. doi: 10.1186/s13073-016-0324-x.
Kim NW (1997) Clinical implications of telomerase in cancer. Eur J Cancer 33: 781-786.
Kumaki F, Kawai T, Hiroi S, Shinomiya N, Ozeki Y, Ferrans VJ, Torikata C (2001) Telomerase activity and expression of human telomerase RNA component and human telomerase reverse transcriptase in lung carcinomas. Hum Pathol 32: 188-195.
Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using Real-Time Quantitative PCR and the 2 -ΔΔCT method. Methods 25: 402–408.
Lu C, Soria JC, Tang X, Xu XC, Wang L, Mao L, Lotan R, Kemp B, Bekele BN, Feng L, Hong WK, Khuri FR (2004) Prognostic factors in resected stage I non-small-cell lung cancer: a multivariate analysis of six molecular markers. J Clin Oncol 22: 4575-4583.
Marchetti A, Bertacca G, Buttitta F, Chella A, Quattrocolo G, Angeletti CA, Bevilacqua G (1999) Telomerase activity as a prognostic indicator in stage I non-small cell lung cancer. Clin Cancer Res 5: 2077-2081.
Marchetti A, Pellegrini C, Buttitta F, Falleni M, Romagnoli S, Felicioni L, Barassi F, Salvatore S, Chella A, Angeletti CA, Roncalli M, Coggi G, Bosari S (2002) Prediction of survival in stage I lung carcinoma patients by telomerase function evaluation. Lab Invest 82: 729-736.
Metzger R, Vallbohmer D, Muller-Tidow C, Higashi H, Bollschweiler E, Warnecke-Eberz U, Brabender J, Baldus SE, Xi H, Berdel WE, Serve H, Hoelscher AH, Schneider PM (2009) Increased human telomerase reverse transcryptase mRNA expression but not telomerase activity is related to survival in curatively resected non-small cell lung cancer. Anticancer Res 29: 1157-1162.
Mocellin S, Pooley KA, Nitti D (2013) Telomerase and the search for the end of cancer. Trends Mol Med 19: 125-33. doi: 10.1016/j.molmed.2012.11.006.
Palm W, de Lange T (2008) How shelterin protects mammalian telomeres. Annu Rev Genet 42: 301-334. doi: 10.1146/annurev.genet.41.110306.130350.
Parkin DM, Bray F, Ferlay J, Pisani P (2005) Global cancer statistics 2002. CA Cancer J Clin 55: 74-108.
Radziszewska A, Kaczmarek-Borowska B, Gradalska-Lampart A, Filip AA (2015) Epidemiology, prevention and risk morbidity factors for lung cancer. Pol Med J 37:113-118.
Shay JW, Bacchetti S (1997) A survey of telomerase activity in human cancer. Eur J Cancer 33: 787-791.
Shay JW, Wright WE (2000) Hayflick, his limit, and cellular ageing. Nat Rev Mol Cell Biol 1: 72-76. doi:10.1038/35036093
Shay JW, Wright WE (2005) Senescence and immortalization: role of telomeres and telomerase. Carcinogenesis 26: 867-74.
Specht K, Richter T, Müller U, Walch A, Werner M, Höfle H (2001) Quantitative gene expression analysis in microdissected archival formalin-fixed and paraffin-embedded tumor tissue. Am J Pathol 158: 419–429. doi: 10.1016/S0002-9440(10)63985-5.
Van den Berg RM, Brokx H, Vesin A, Field JK, Brambilla C, Meijer CJ, Sutedja GT, Heideman DA, Postmus PE, Smit EF, Snijders PJ (2010) Prognostic value of hTERT mRNA expression in surgical samples of lung cancer patients: the European Early Lung Cancer Project. Int J Oncol 37: 455-461.
Wang L, Soria J-Ch, Kemp BL, Liu DD, Mao L, Khuri FR (2002) hTERT expression is a prognostic factor of survival in patients with stage I non-smal cell lung cancer. Clin Cancer Res 8: 2883-2889.
Weinrich SL, Pruzan R, Ma L, Ouellette M, Tesmer VM, Holt SE, Bodnar AG, Lichtsteiner S, Kim NW, Trager JB, Taylor RD, Carlos R, Andrews WH, Wright WE, Shay JW, Harley CB, Morin GB (1997) Reconstitution of human telomerase with the template RNA component hTR and the catalytic protein subunit hTRT. Nat Genet 17: 498-502.
Acta Biochimica Polonica is an OpenAccess quarterly and publishes four issues a year. All contents are distributed under the Creative Commons Attribution-ShareAlike 4.0 International (CC BY 4.0) license. Everybody may use the content following terms: Attribution — You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use.
Copyright for all published papers © stays with the authors.
Copyright for the journal: © Polish Biochemical Society.