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 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. 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. 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.

Our main aim consists of investigating the clinical usefulness of gelatinases and their tissue inhibitors in non-small cell lung cancer (NSCLC). Thus, we have analysed in 111 NSCLCs, levels and activity of MMP-2, MMP-9, TIMP-1 and TIMP-2, by Enzymoimmunoassay and Gelatine zymography, respectively. Our data revealed higher MMP-2 net activity in the NSCLC population analyzed in this study, this parameter showing a significant association with the TNM stage of tumours (P=0.002). Moreover, MMP-9 levels were significantly associated with poor clinical evolution of patients (P=0.02). Also, disease-free survival time was higher for patients whose tumours showed TIMP-1 increased levels (P=0.04). Of interest, Cox multivariate analysis revealed that TIMP-1 levels can be considered as an independent prognostic factor in NSCLC. Relative Risk (RR) to tumour relapse was more than two times lower for patients showing high TIMP-1 levels (RR=0.420, P=0.041). Therefore, according to our results, we conclude that MMP-9 and TIMP-1 levels of synthesis could be useful for the selection of patients with potentially unfavourable clinical evolution in order to establish adjuvant therapy protocols. Among these parameters, TIMP-1 level evaluation emerges as the main factor to predict the clinical outcome of patients.