title: Prognostic value of telomere function in gastric cancers with and without microsatellite instability.
abstract: OBJECTIVE
  To identify molecular markers that may be useful in the selection of gastric cancer patients with different prognoses, we investigated telomere function in gastric cancers with and without microsatellite instability (MSI).
  
  
  METHODS
  We analyzed 83 gastric cancers and its paired-normal tissues to investigate MSI and telomere function. MSI was established using five polymorphic human repeat DNA markers. Telomere function was evaluated by determining telomerase activity, telomere length, and telomere-repeat factors 1 and 2 (TRF1 and TRF2) expression.
  
  
  RESULTS
  Patients with high microsatellite instability (MSI-H) gastric cancers showed a significantly better prognosis than those affected by microsatellite stable or low microsatellite instability (MSS/MSI-L) tumors (P = 0.03). The lowest expression levels of TRF1 and TRF2 were associated with MSI-H gastric cancers (P = 0.008 and 0.006, respectively). Moreover, a clear trend toward a worse prognosis was found in the group of patients who had tumors with the shortest telomeres (P = 0.01). Cox multivariate analysis showed that MSI emerged as a protective prognostic factor; MSS/MSI-L tumors conferred a significantly poor prognosis in patients (relative risk = 4.862-fold greater than the MSI-H group) (P = 0.033). Telomere length of gastric tumors less than 2.86 kbp was a factor that led to a poor prognosis (relative risk = 4.420, with respect to tumors showing telomere length ≥ 2.86 kbp) (P = 0.002).
  
  
  CONCLUSIONS
  We propose telomere status as a potential molecular marker with usefulness in the establishment of the prognosis of gastric cancers both for the mutator phenotype and for the suppressor pathway.
authors.affiliation: aDepartment of Biochemistry and Molecular Biology II, Faculty of Pharmacy, Complutense University bSurgery Service, San Carlos Hospital, Institute for Health Research from San Carlos Hospital (IdISSC), Madrid, Spain.
authors.forename: Irene
authors.initials: I
authors.lastname: Pascua
authors.forename: Tamara
authors.initials: T
authors.lastname: Fernández-Marcelo
authors.forename: Andrés
authors.initials: A
authors.lastname: Sánchez-Pernaute
authors.forename: Carmen
authors.initials: C
authors.lastname: de Juan
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Head
authors.forename: Antonio-José
authors.initials: AJ
authors.lastname: Torres-García
authors.forename: Pilar
authors.initials: P
authors.lastname: Iniesta
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology / Q000556:secondary; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D053842:Microsatellite Instability; D009367:Neoplasm Staging; D011379:Prognosis; D013274:Stomach Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D016615:Telomere / Q000502:physiology*; D035321:Telomeric Repeat Binding Protein 1 / Q000378:metabolism; D035341:Telomeric Repeat Binding Protein 2 / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; C504753:TERF2 protein, human; D035321:Telomeric Repeat Binding Protein 1; D035341:Telomeric Repeat Binding Protein 2