title: The associations of TERT-CLPTM1L variants and TERT mRNA expression with the prognosis of early stage non-small cell lung cancer.
abstract: Lung cancer is the leading cause of cancer-related death in the world. Several genome-wide association studies (GWAS) have identified TERT-CLPTM1L as plausible causative locus for lung cancer development. This study aimed to investigate the associations of genetic variations in TERT-CLPTM1L and the expression level of TERT with the survival of early stage non-small cell lung cancer (NSCLC) patients. We selected three single-nucleotide polymorphisms of TERT-CLPTM1L (rs2853669, rs2736108 and rs31490) and genotyped in 140 early stage NSCLC patients by TaqMan assay. Associations between these variations and survival outcome of early stage NSCLC patients were further investigated. We also used TCGA data to evaluate the associations of TERT messenger RNA (mRNA) expression and survival outcome of early stage NSCLC patients. Survival analysis showed that, compared with early NSCLC patients carrying TERT rs2853669 TT+TC genotypes, patients with rs2853669 CC genotype had significantly longer median survival time (MST=102.2 vs 52.4 months; log-rank P=0.028) and lower death risk [hazard ratio (HR) with 95% confidence interval (CI))=0.38(0.17-0.82), P=0.014]. Early NSCLC patients carrying TERT rs2736108 AA genotype had significantly shorter MST (MST=29.0 vs 63.3 months; log-rank P=0.020) and increased death risk [HR (95% CI)=2.22(1.01-5.80), P=0.046], when compared with patients carrying rs2736108 GG genotypes. TCGA data revealed that early NSCLC patients with higher expression level of TERT mRNA in lung tumor tissues had a longer MST and decreased death risk than those with low expression level of TERT mRNA [MST=54.4 vs 49.0 months; log-rank P=0.041; adjusted HR (95% CI)=0.68(0.50-0.94)]. These findings may add potential evidence to understand the prognostic value of TERT and provide a new prospect of individualized prevention and treatment for early stage NSCLC.
authors.affiliation: Department of Occupational and Environmental Health, State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Oncology, Wuhan Iron and Steel (Group) Corporation Staff-Worker Hospital, Wuhan, China.
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Occupational and Environmental Health, State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Bai
authors.affiliation: Department of Occupational and Environmental Health, State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: S
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Oncology, Wuhan Iron and Steel (Group) Corporation Staff-Worker Hospital, Wuhan, China.
authors.forename: X
authors.initials: X
authors.lastname: Yin
authors.affiliation: Department of Oncology, Wuhan Iron and Steel (Group) Corporation Staff-Worker Hospital, Wuhan, China.
authors.forename: J
authors.initials: J
authors.lastname: Xiang
authors.affiliation: Department of Occupational and Environmental Health, State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: X
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Occupational and Environmental Health, State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: M
authors.initials: M
authors.lastname: He
authors.affiliation: Department of Occupational and Environmental Health, State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Occupational and Environmental Health, State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: T
authors.initials: T
authors.lastname: Wu
authors.affiliation: Department of Oncology, Wuhan Iron and Steel (Group) Corporation Staff-Worker Hospital, Wuhan, China.
authors.forename: P
authors.initials: P
authors.lastname: Xu
authors.affiliation: Department of Occupational and Environmental Health, State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: H
authors.initials: H
authors.lastname: Guo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D003131:Combined Modality Therapy; D005260:Female; D005500:Follow-Up Studies; D015870:Gene Expression; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D016016:Proportional Hazards Models; D040641:Quantitative Trait Loci; D012333:RNA, Messenger; D019098:Telomerase / Q000235:genetics*
chemical_list: C422445:CLPTM1L protein, human; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; C509186:TERT protein, human; D019098:Telomerase