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Prognostic value of telomere function in gastric cancers with and without microsatellite instability

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Pascua García, Irene and Fernández Marcelo, Tamara and Sánchez Pernaute, Andrés and Juan, Carmen de and Head, Jacqueline and Torres García, Antonio José and Iniesta, Pilar (2015) Prognostic value of telomere function in gastric cancers with and without microsatellite instability. European Journal of Gastroenterology and Hepatology, 27 . pp. 162-169. ISSN 0954-691X

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Official URL: http://dx.doi.org/10.1097/MEG.0000000000000250



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).
Materials and 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).
Conclusion 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.


Item Type:Article
Uncontrolled Keywords:Gastric cancer, microsatellite instability, telomere, telomere-binding proteins
Subjects:Medical sciences > Pharmacy > Biochemistry
ID Code:33314
Deposited On:25 Sep 2015 09:42
Last Modified:28 Sep 2015 08:22

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