Abstract
BackgroundConsidering 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).MethodsTelomere 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.ResultsOverall, 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.ConclusionsTelomerase 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.
Highlights
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)
Telomere status and telomerase activity in tissue samples We evaluated telomere length in a total of 284 lung tissue samples: 142 NSCLCs and the corresponding non-tumour samples
Telomere status and telomerase activity: correlation with clinical variables of non-small cell lung tumours As it is showed in the Table 1, there was a statistically significant association between the telomere length and the size of the primary tumour (T), (P = 0.006; Kruskal-Wallis test): T1 tumours had shorter telomeres than both T2 and T3 tumours
Summary
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). Of fundamental concern is the identification and use of new biomarkers, with high specificity and sensitivity, which will allow the prediction of the disease course and identification of patients who would or would not benefit from specific therapy. In this way, telomere function has been recognized as possible biomarker [2].
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