Hai QIU, Xue-Cheng XIE, Lian-Ying GE, Hao LAI, Fan TANG, Yu-Zhou QIN

The Relationship between Telomerase Activity and Clinicopathological Parameters in Colorectal Cancer: A Meta-Analysis

Background:Recently, accumulated research has found that the expression of telomerase activity (TA) was associated with colorectal cancer (CRC) advance-ment, whereas the TA prognostic effect in CRC patients is still controversial. Aims: To investigate relationships between TA and CRC clinicopathological parameters.Study Design: Meta-analysis study.Methods: We searched published studies in databases, such as EMBASE, the Cochrane Library, PubMed, and Ovid databases (last search updated to October 2014) by meeting specified search criteria. The quality of the included studies was usually evaluated and a meta-analysis was implemented by Stata 12.0 software. We used an odds ratio (OR) with a 95% confidence interval (CI) to evaluate relationship strengths between TA and CRC clinicopathological parameters.Results: In total, 11 studies (715 patients) were in-cluded to assess the relation between TA and metas-tasis-related parameters in CRC patients. The results indicate that a senior TA expression was connected with the existence of lymph node metastasis (180 pa-tients; OR=2.85, 95% CI=1.40-5.81, p=0.004), and tu-mor site (522 patients; OR=2.93, 95% CI=1.29-6.67, p=0.010). However, a senior TA expression was not connected with tumor size (137 patients; OR=1.57, 95% CI=0.71-3.47, p=0.267), histological differen-tiation (570 patients; OR=1.28, 95% CI=0.78-2.09, p=0.332), depth of invasion (57 patients; OR=3.76, 95% CI=0.61-23.04, p=0.152), distant metastasis (123 patients; OR=1.76, 95% CI=0.54-5.74, p=0.346), and clinical stage of the cancer (543 patients; OR=1.59, 95% CI=0.74-3.38, p=0.232).Conclusion: This meta-analysis suggests that a positive TA was correlated with lymph node metastasis progres-sion and tumor site of the CRC but did not correlate with other important clinicopathological parameters. TA can play a useful part in the prognosis and treatment of CRC patients, but further studies are required to confirm this

PDF

___

Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin 2013;63:11-30.
O'Connell JB, Maggard MA, Ko CY. Colon cancer survival rates with the new American Joint Committee on Cancer sixth edition staging. J N Cancer Inst 2004;96:1420-5.
Hegde MV, Mali AV, Chandorkar SS. What is a cancer cell? Why does it metastasize? Asian Pac J Cancer Prev 2013;14:3987-9.
Podlevsky JD, Chen JJ. It all comes together at the ends: telom- erase structure, function, and biogenesis. Mutat Res 2012;730:3- 11.
Feng J, Funk WD, Wang SS, Weinrich SL, Avilion AA, Chiu CP, et al. The RNA component of human telomerase. Science 1995;269:1236-41.
Cukusic A, Skrobot Vidacek N, Sopta M, Rubelj I. Telomerase regulation at the crossroads of cell fate. Cytogenet Genome Res 2008;122:263-72.
Chen CH, Chen RJ. Prevalence of telomerase activity in human cancer. J Formos Med Assoc 2011;110:275-89.
Valls Bautista C, Pinol Felis C, Rene Espinet JM, Buenestado Garcia J, Vinas Salas J. Telomerase activity and telomere length in the colorectal polyp-carcinoma sequence. Rev Esp Enferm Dig 2009;101:179-86.
Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, et al. Meta-analysis of observational studies in epi- demiology: a proposal for reporting. Meta-analysis Of Obser- vational Studies in Epidemiology (MOOSE) group. JAMA 2000;283:2008-12.
Poole JC, Andrews LG, Tollefsbol TO. Activity, function, and gene regulation of the catalytic subunit of telomerase (hTERT). Gene 2001;269:1-12.
Tahara H, Yasui W, Tahara E, Fujimoto J, Ito K, Tamai K, et al. Immuno-histochemical detection of human telomerase catalytic component, hTERT, in human colorectal tumor and non-tumor tissue sections. Oncogene 1999;18:1561-7.
Wells GA, Shea B, O'Connell D, Peterson J, Welch V, Losos M, et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality if nonrandomized studies in meta-analyses.
Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ (Clinical research ed) 2003;327:557-60.
Begg CB, Mazumdar M. Operating characteristics of a rank cor- relation test for publication bias. Biometrics 1994;50:1088-101.
Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta- analysis detected by a simple, graphical test. BMJ 1997;315:629- 34.
Brown T, Aldous W, Lance R, Blaser J, Baker T, Williard W. The association between telomerase, p53, and clinical staging in colorectal cancer. Am J Surg 1998;175:364-6.
Okayasu I, Mitomi H, Yamashita K, Mikami T, Fujiwara M, Kato M, et al. Telomerase activity significantly correlates with cell differentiation, proliferation and lymph node metastasis in colorectal carcinomas. J Cancer Res Clin Oncol 1998;124:444- 9.
Tatsumoto N, Hiyama E, Murakami Y, Imamura Y, Shay JW, Matsuura Y, et al. High telomerase activity is an independent prognostic indicator of poor outcome in colorectal cancer. Clin Cancer Res 2000;6:2696-701.
Vidaurreta M, Maestro ML, Rafael S, Veganzones S, Sanz-Casla MT, Cerdan J, et al. Telomerase activity in colorectal cancer, prognostic factor and implications in the microsatellite instabil- ity pathway. World J Gastroenterol 2007;13:3868-72.
Tahara H, Kuniyasu H, Yokozaki H, Yasui W, Shay JW, Ide T, et al. Telomerase activity in preneoplastic and neoplastic gastric and colorectal lesions. Clin Cancer Res 1995;1:1245-51.
Yoshida K, Sugino T, Goodison S, Warren BF, Nolan D, Wad- sworth S, et al. Detection of telomerase activity in exfoliated cancer cells in colonic luminal washings and its related clinical implications. Br J Cancer 1997;75:548-53.
Sanz-Casla MT, Vidaurreta M, Sanchez-Rueda D, Maestro ML, Arroyo M, Cerdan FJ. Telomerase activity as a prognostic factor in colorectal cancer. Onkologie 2005;28:553-7.
Garcia-Aranda C, de Juan C, Diaz-Lopez A, Sanchez-Pernaute A, Torres AJ, Diaz-Rubio E, et al. Correlations of telomere length, telomerase activity, and telomeric-repeat binding factor 1 expression in colorectal carcinoma. Cancer 2006;106:541-51.
Zhao D, Zhang W, Jin S. Study of telomerase activity in colorec- tal carcinomas. Zhonghua Zhong Liu Za Zhi 1998;20:199-201.
Fang DC, Young J, Luo YH, Lu R, Jass J. Detection of telomer- ase activity in biopsy samples of colorectal cancer. J Gastroen- terol Hepatol 1999;14:328-32.
Kawanishi-Tabata R, Lopez F, Fratantonio S, Kim N, Goldblum J, Tubbs R, et al. Telomerase activity in stage II colorectal carci- noma. Cancer 2002;95:1834-9.
Dukes CE. The classification of cancer of the rectum. J Pathol Bacteriol 1932;35:323-32.
Jass JR, Love SB, Northover JM. A new prognostic classifica- tion of rectal cancer. Lancet 1987;1:1303-6.
Westra JL, Schaapveld M, Hollema H, de Boer JP, Kraak MM, de Jong D, et al. Determination of TP53 mutation is more rel- evant than microsatellite instability status for the prediction of disease-free survival in adjuvant-treated stage III colon cancer patients. J Clin Oncol 2005;23:5635-43.
Roth AD, Tejpar S, Delorenzi M, Yan P, Fiocca R, Klingbiel D, et al. Prognostic role of KRAS and BRAF in stage II and III resected colon cancer: results of the translational study on the PETACC-3, EORTC 40993, SAKK 60-00 trial. J Clin Oncol 2010;28:466-74.
Ghori A, Usselmann B, Ferryman S, Morris A, Fraser I. Telom- erase expression of malignant epithelial cells correlates with Dukes' stage in colorectal cancer. Colorectal Dis 2002;4:441-6.
Lü MH, Deng JQ, Cao YL, Fang DC, Zhang Y, Yang SM. Prog- nostic role of telomerase activity in gastric adenocarcinoma: A meta-analysis. Exp Ther Med 2012;3:728-34.
Chang GJ, Rodriguez-Bigas MA, Skibber JM, Moyer VA. Lymph node evaluation and survival after curative resection of colon cancer: systematic review. J Natl Cancer Inst 2007;99:433-41.
Maehara Y, Oshiro T, Endo K, Baba H, Oda S, Ichiyoshi Y, et al. Clinical significance of occult micrometastasis lymph nodes from patients with early gastric cancer who died of recurrence. Surgery 1996;119:397-402.
Chua YJ, Zalcberg JR. Progress and challenges in the adjuvant treatment of stage II and III colon cancers. Expert Revanticancer Ther 2008;8:595-604.
Wolpin BM, Mayer RJ. Systemic treatment of colorectal cancer. Gastroenterology 2008;134:1296-310.
Jin X, Beck S, Sohn YW, Kim JK, Kim SH, Yin J, et al. Human telomerase catalytic subunit (hTERT) suppresses p53-mediated anti-apoptotic response via induction of basic fibroblast growth factor. Exp Mol Med 2010;42:574-82.
Bagheri S, Nosrati M, Li S, Fong S, Torabian S, Rangel J, et al. Genes and pathways downstream of telomerase in melanoma metastasis. Proc Natl Acad Sci USA 2006;103:11306-11.
Geserick C, Tejera A, Gonzalez-Suarez E, Klatt P, Blasco MA. Expression of mTert in primary murine cells links the growth- promoting effects of telomerase to transforming growth factor- beta signaling. Oncogene 2006;25:4310-9.
Smith LL, Coller HA, Roberts JM. Telomerase modulates ex- pression of growth-controlling genes and enhances cell prolif- eration. Nat Cell Biol 2003;5:474-9.
Kojima K, Hiyama E, Otani K, Ohtaki M, Fukuba I, Fukuda E, et al. Telomerase activation without shortening of telomeric 3'-overhang is a poor prognostic factor in human colorectal can- cer. Cancer Sci 2011;102:330-5.
Saleh S, Lam AK, Ho YH. Real-time PCR quantification of hu- man telomerase reverse transcriptase (hTERT) in colorectal can- cer. Pathology 2008;40:25-30.
Bertorelle R, Briarava M, Rampazzo E, Biasini L, Agostini M, Maretto I, et al. Telomerase is an independent prognostic marker of overall survival in patients with colorectal cancer. Br J Can- cer 2013;108:278-84.
Ayiomamitis GD, Notas G, Zaravinos A, Zizi-Sermpetzoglou A, Georgiadou M, Sfakianaki O, et al. Differences in telomerase ac- tivity between colon and rectal cancer. Can J Surg 2014;57:199- 208.