Ping Yuan1, Sha Huang2, Fei-Chao Bao3, Jin-Lin Cao2, Hong-Xu Sheng2, Liang Shi4, Wang Lv2, Jian Hu5. 1. Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, 1 Jianshe Ave, Zhengzhou, Henan, 450000, China; Department of Thoracic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Ave, Hangzhou, Zhejiang, 310003, China. Electronic address: yuanping@zju.edu.cn. 2. Department of Thoracic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Ave, Hangzhou, Zhejiang, 310003, China. 3. Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, 241 Huaihai Road, Shanghai, 200030, China. 4. Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University, Hangzhou 310016, 3 Qingchun Ave, Hangzhou, Zhejiang, 310000, China. 5. Department of Thoracic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Ave, Hangzhou, Zhejiang, 310003, China. Electronic address: dr_hujian@zju.edu.cn.
Abstract
BACKGROUND: The role of epidermal growth factor receptor (EGFR) pathways in regulating telomerase is increasingly being recognised. We analysed the impact of rs2853669 single nucleotide polymorphism (SNP) on telomere parameters and its prognostic value for non-small cell lung cancer (NSCLC) with or without EGFR mutation. METHODS: The association of rs2853669 with telomerase reverse transcriptase (TERT) mRNA level and relative telomere length (RTL) was analysed using resected tumour samples from 250 NSCLC patients. We also investigated the patients' clinical outcomes with a median follow-up of 57 months (2-99 months). RESULTS: The rs2853669 T/C allele was significantly associated with lower TERT mRNA expression (versus C/C and versus T/T; p < 0.001 for both) and shorter RTL (versus C/C and versus T/T; p = 0.039 and 0.023) in patients without EGFR mutation. Such difference was not observed in their counterparts harbouring EGFR mutation. When considering the cohort as a whole, T/C allele was significantly associated with shortest overall survival compared with T/T or C/C allele (mean: 61.8, 80.9 and 88.7 months, plog-rank < 0.001) and disease-free survival (mean: 78.3, 87.9 and 91.5 months, plog-rank = 0.019). Stratification analyses showed that the negative prognostic effect of T/C on OS was constrained in patients without EGFR mutation. CONCLUSION: Our study revealed significant associations of a common SNP within TERT promoter region on telomere parameters and survival in NSCLC patients without EGFR mutation. The result may help providing instruction for therapeutic interventions targeting telomerase and evidence for investigation of TERT-EGFR interacting mechanism in telomere biology.
BACKGROUND: The role of epidermal growth factor receptor (EGFR) pathways in regulating telomerase is increasingly being recognised. We analysed the impact of rs2853669 single nucleotide polymorphism (SNP) on telomere parameters and its prognostic value for non-small cell lung cancer (NSCLC) with or without EGFR mutation. METHODS: The association of rs2853669 with telomerase reverse transcriptase (TERT) mRNA level and relative telomere length (RTL) was analysed using resected tumour samples from 250 NSCLCpatients. We also investigated the patients' clinical outcomes with a median follow-up of 57 months (2-99 months). RESULTS: The rs2853669 T/C allele was significantly associated with lower TERT mRNA expression (versus C/C and versus T/T; p < 0.001 for both) and shorter RTL (versus C/C and versus T/T; p = 0.039 and 0.023) in patients without EGFR mutation. Such difference was not observed in their counterparts harbouring EGFR mutation. When considering the cohort as a whole, T/C allele was significantly associated with shortest overall survival compared with T/T or C/C allele (mean: 61.8, 80.9 and 88.7 months, plog-rank < 0.001) and disease-free survival (mean: 78.3, 87.9 and 91.5 months, plog-rank = 0.019). Stratification analyses showed that the negative prognostic effect of T/C on OS was constrained in patients without EGFR mutation. CONCLUSION: Our study revealed significant associations of a common SNP within TERT promoter region on telomere parameters and survival in NSCLCpatients without EGFR mutation. The result may help providing instruction for therapeutic interventions targeting telomerase and evidence for investigation of TERT-EGFR interacting mechanism in telomere biology.