title: Clinical Relevance of Telomere Status and Telomerase Activity in Colorectal Cancer.
abstract: The role of telomeres and telomerase in colorectal cancer (CRC) is well established as the major driving force in generating chromosomal instability. However, their potential as prognostic markers remains unclear. We investigated the outcome implications of telomeres and telomerase in this tumour type. We considered telomere length (TL), ratio of telomere length in cancer to non-cancer tissue (T/N ratio), telomerase activity and TERT levels; their relation with clinical variables and their role as prognostic markers. We analyzed 132 CRCs and paired non-cancer tissues. Kaplan-Meier curves for disease-free survival were calculated for TL, T/N ratio, telomerase activity and TERT levels. Overall, tumours had shorter telomeres than non-tumour tissues (P < 0.001) and more than 80% of CRCs displayed telomerase activity. Telomere lengths of non-tumour tissues and CRCs were positively correlated (P < 0.001). Considering telomere status and clinical variables, the lowest degree of telomere shortening was shown by tumours located in the rectum (P = 0.021). Regarding prognosis studies, patients with tumours showing a mean TL < 6.35 Kb experienced a significantly better clinical evolution (P < 0.001) and none of them with the highest degree of tumour telomere shortening relapsed during the follow-up period (P = 0.043). The mean TL in CRCs emerged as an independent prognostic factor in the Cox analysis (P = 0.017). Telomerase-positive activity was identified as a marker that confers a trend toward a poor prognosis. In CRC, our results support the use of telomere status as an independent prognostic factor. Telomere status may contribute to explaining the different molecular identities of this tumour type.
authors.affiliation: Department of Biochemistry and Molecular Biology II, Faculty of Pharmacy, Complutense University, 28040-Madrid, Spain.|Sanitary Research Institute of San Carlos Hospital (IdISSC), 28040-Madrid, Spain.
authors.forename: Tamara
authors.initials: T
authors.lastname: Fernández-Marcelo
authors.affiliation: Service of General Surgery and Digestive Tract, San Carlos Hospital, 28040-Madrid, Spain.|Sanitary Research Institute of San Carlos Hospital (IdISSC), 28040-Madrid, Spain.
authors.forename: Andrés
authors.initials: A
authors.lastname: Sánchez-Pernaute
authors.affiliation: Department of Biochemistry and Molecular Biology II, Faculty of Pharmacy, Complutense University, 28040-Madrid, Spain.|Sanitary Research Institute of San Carlos Hospital (IdISSC), 28040-Madrid, Spain.
authors.forename: Irene
authors.initials: I
authors.lastname: Pascua
authors.affiliation: Department of Biochemistry and Molecular Biology II, Faculty of Pharmacy, Complutense University, 28040-Madrid, Spain.|Sanitary Research Institute of San Carlos Hospital (IdISSC), 28040-Madrid, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: De Juan
authors.affiliation: Department of Biochemistry and Molecular Biology II, Faculty of Pharmacy, Complutense University, 28040-Madrid, Spain.|Sanitary Research Institute of San Carlos Hospital (IdISSC), 28040-Madrid, Spain.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Head
authors.affiliation: Service of General Surgery and Digestive Tract, San Carlos Hospital, 28040-Madrid, Spain.|Sanitary Research Institute of San Carlos Hospital (IdISSC), 28040-Madrid, Spain.
authors.forename: Antonio-José
authors.initials: AJ
authors.lastname: Torres-García
authors.affiliation: Department of Biochemistry and Molecular Biology II, Faculty of Pharmacy, Complutense University, 28040-Madrid, Spain.|Sanitary Research Institute of San Carlos Hospital (IdISSC), 28040-Madrid, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Iniesta
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D009367:Neoplasm Staging; D011379:Prognosis; D019098:Telomerase / Q000378:metabolism*; D016615:Telomere / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D019098:Telomerase