title: Telomere length and telomerase activity in non-small cell lung cancer prognosis: clinical usefulness of a specific telomere status.
abstract: BACKGROUND
  Considering previous data and the need to incorporate new biomarkers for the prognosis of solid tumours into the clinic, our aim in this work consists of evaluating the potential clinical use of telomeres and telomerase in non-small cell lung cancer (NSCLC).
  
  
  METHODS
  Telomere status was established by determination of telomere length using the Terminal Restriction Fragment length method, and telomerase activity by the Telomeric Repeat Amplification Protocol in 142 NSCLCs and their corresponding control samples, obtained from patients submitted to surgery. Group-oriented curves for disease-free survival were calculated according to the Kaplan-Meier method considering telomere length, T/N ratio (telomere length in tumour to control tissue) and telomerase activity.
  
  
  RESULTS
  Overall, tumours had significantly shorter telomeres compared with telomeres in control tissues (P = 0.027). More than 80 % of NSCLCs displayed telomerase activity. Regarding prognosis studies, patients whose tumours showed a mean telomere length (MTL) <7.29 Kb or T/N ratio <0.97 showed a significantly poor clinical evolution (P = 0.034 and P = 0.040, respectively). As result of a Cox multivariate analysis including pathologic state and lymph node dissemination, the MTL and T/N ratio emerged as independent significant prognostic factors.
  
  
  CONCLUSIONS
  Telomerase activity was identified as a marker of poor prognosis. The novel finding of this study is the independent prognosis role of a specific telomere status in NSCLC patients. According to our results, telomere function may emerge as a useful molecular tool that allow to select groups of NSCLC patients with different clinical evolution, in order to establish personalized therapy protocols.
authors.affiliation: Department of Biochemistry and Molecular Biology II. Faculty of Pharmacy, Complutense University, Sq. Ramón y Cajal s/n (Ciudad Universitaria), Madrid, 28040, Spain. tafernan@ucm.es.|Sanitary Research Institute of San Carlos Hospital (IdISSC), Madrid, 28040, Spain. tafernan@ucm.es.
authors.forename: Tamara
authors.initials: T
authors.lastname: Fernández-Marcelo
authors.affiliation: Service of Thoracic Surgery, San Carlos Hospital, Madrid, 28040, Spain. agm912@hotmail.com.|Sanitary Research Institute of San Carlos Hospital (IdISSC), Madrid, 28040, Spain. agm912@hotmail.com.
authors.forename: Ana
authors.initials: A
authors.lastname: Gómez
authors.affiliation: Department of Biochemistry and Molecular Biology II. Faculty of Pharmacy, Complutense University, Sq. Ramón y Cajal s/n (Ciudad Universitaria), Madrid, 28040, Spain. ipascuag@ucm.es.|Sanitary Research Institute of San Carlos Hospital (IdISSC), Madrid, 28040, Spain. ipascuag@ucm.es.
authors.forename: Irene
authors.initials: I
authors.lastname: Pascua
authors.affiliation: Department of Biochemistry and Molecular Biology II. Faculty of Pharmacy, Complutense University, Sq. Ramón y Cajal s/n (Ciudad Universitaria), Madrid, 28040, Spain. juchoca@ucm.es.|Sanitary Research Institute of San Carlos Hospital (IdISSC), Madrid, 28040, Spain. juchoca@ucm.es.
authors.forename: Carmen
authors.initials: C
authors.lastname: de Juan
authors.affiliation: Department of Biochemistry and Molecular Biology II. Faculty of Pharmacy, Complutense University, Sq. Ramón y Cajal s/n (Ciudad Universitaria), Madrid, 28040, Spain. jacquelinehead@farm.ucm.es.|Sanitary Research Institute of San Carlos Hospital (IdISSC), Madrid, 28040, Spain. jacquelinehead@farm.ucm.es.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Head
authors.affiliation: Service of Thoracic Surgery, San Carlos Hospital, Madrid, 28040, Spain. fhtrancho@hotmail.com.|Sanitary Research Institute of San Carlos Hospital (IdISSC), Madrid, 28040, Spain. fhtrancho@hotmail.com.
authors.forename: Florentino
authors.initials: F
authors.lastname: Hernando
authors.affiliation: Service of Thoracic Surgery, San Carlos Hospital, Madrid, 28040, Spain. jrjarabo@hotmail.com.|Sanitary Research Institute of San Carlos Hospital (IdISSC), Madrid, 28040, Spain. jrjarabo@hotmail.com.
authors.forename: Jose-Ramón
authors.initials: JR
authors.lastname: Jarabo
authors.affiliation: Service of Thoracic Surgery, San Carlos Hospital, Madrid, 28040, Spain. jcgastardi@hotmail.com.|Sanitary Research Institute of San Carlos Hospital (IdISSC), Madrid, 28040, Spain. jcgastardi@hotmail.com.
authors.forename: Joaquín
authors.initials: J
authors.lastname: Calatayud
authors.affiliation: Service of General Surgery and Digestive Tract, San Carlos Hospital, Madrid, 28040, Spain. ajtorresgarcia@gmail.com.|Sanitary Research Institute of San Carlos Hospital (IdISSC), Madrid, 28040, Spain. ajtorresgarcia@gmail.com.
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, Sq. Ramón y Cajal s/n (Ciudad Universitaria), Madrid, 28040, Spain. insepi@ucm.es.|Sanitary Research Institute of San Carlos Hospital (IdISSC), Madrid, 28040, Spain. insepi@ucm.es.
authors.forename: Pilar
authors.initials: P
authors.lastname: Iniesta
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D011379:Prognosis; D019098:Telomerase / Q000235:genetics*; D016615:Telomere / Q000378:metabolism*
chemical_list: D019098:Telomerase