Abstract 4019: High TERT expression in NSCLC is associated with poor prognosis

Abstract

Abstract Background: Activation of human telomerase reverse transcriptase (TERT) has been linked to tumorigenesis and aggressive tumor behavior. This study was undertaken to evaluate if TERT expression was correlated with clinicopathological parameters and survival in patients with non-small cell lung cancer (NSCLC). Methods: TMA slides made from 254 NSCLC patients (cohort 1 and cohort 2), including 127 adenocarcinoma (LUAD), 78 squamous carcinomas (LUSC) and 46 other types, were included. TMA Formalin-fixed and paraffin-embedded (FFPE) tissue sections were stained using the immunohistochemistry stain (IHC). The percentage of positive nuclei was determined for each case and the cut-off value was set as 5%, 20% and 50% positive tumor cells. TERT expression levels were analyzed for associations with patient survival rates and clinicopathological parameters (such as age, gender, tumor grade, tumor stage, metastasis). Survival analysis was performed using the Kaplan-Meier method. Results: TERT was positive in 199/254 (78%) of the samples. High TERT expression was seen in tumor specimens compared with normal adjunct tissues (p < 0.001). Kaplan-Meier curves indicated that high TERT expression was significantly associated with poor overall survival in NSCLC patients (p < 0.001 and p < 0.0001, 20% and 50% cut-off, respectively). Multivariate analysis of survival demonstrated that TERT expression at 50% cutoff was an independent prognostic factor for NSCLC patients (HR = 0.1461, 95% CI: 0.0862-0.2475, p < 0.0001). High TERT expression was also associated with short survival of LUSC and LUAD patients at 50% cutoff (p < 0.0001). No significant association with OS was observed at 5% cutoff. There was also significant correlation between TERT expression with metastasis but no correlation with clinical stage, histological type and tumor differentiation. Conclusion: Our study showed that high TERT expression is present in 78% of NSCLC tumors and is associated with poor prognosis. TERT may serve as a prognostic biomarker and novel drug target for NSCLC. Citation Format: Tianhong Li, Weijie Ma, Qianping Li, Sixi Wei, Tao Wang, Jingyi Xiang, Cheng Liu. High TERT expression in NSCLC is associated with poor prognosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4019.