title: Prognostic value analysis of mutational and clinicopathological factors in non-small cell lung cancer.
abstract: BACKGROUND
  Targeting activating oncogenic driver mutations in lung adenocarcinoma has led to prolonged survival in patients harboring these specific genetic alterations. The prognostic value of these mutations has not yet been elucidated. The prevalence of recently uncovered non-coding somatic mutation in promoter region of TERT gene is also to be validated in lung cancer. The purpose of this study is to show the prevalence, association with clinicalpathological features and prognostic value of these factors.
  
  
  METHODS
  In a cohort of patients with non-small cell lung cancer (NSCLC) (n = 174, including 107 lung adenocarcinoma and 67 lung squamous cell carcinoma), EGFR, KRAS, HER2 and BRAF were directly sequenced in lung adeoncarcinoma, ALK fusions were screened using FISH (Fluorescence in situ Hybridization).TERT promoter region was sequenced in all of the 174 NSCLC samples. Associations of these somatic mutations and clinicopathological features, as well as prognostic factors were evaluated.
  
  
  RESULTS
  EGFR, KRAS, HER2, BRAF mutation and ALK fusion were mutated in 25.2%, 6.5%, 1.9%, 0.9% and 3.7% of lung adenocarcinomas. No TERT promoter mutation was validated by reverse-sided sequencing. Lung adenocarcinoma with EGFR and KRAS mutations showed no significant difference in Disease-free Survival (DFS) and Overall Survival (OS). Cox Multi-variate analysis revealed that only N stage and HER2 mutation were independent predictors of worse overall survival (HR = 1.653, 95% CI 1.219-2.241, P = 0.001; HR = 12.344, 95% CI 2.615-58.275, P = 0.002).
  
  
  CONCLUSIONS
  We have further confirmed that TERT promoter mutation may only exist in a very small fraction of NSCLCs. These results indicate that dividing lung adenocarcinoma into molecular subtypes according to oncogenic driver mutations doesn't predict survival difference of the disease.
authors.affiliation: Department of Lung Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China; Key Laboratory of Cancer Prevention and Therapy, Tianjin, China; Tianjin Lung Cancer Center, Tianjin, China.
authors.forename: Chenguang
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Lung Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China; Key Laboratory of Cancer Prevention and Therapy, Tianjin, China; Tianjin Lung Cancer Center, Tianjin, China.
authors.forename: Ligang
authors.initials: L
authors.lastname: Hao
authors.affiliation: Department of Lung Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China; Key Laboratory of Cancer Prevention and Therapy, Tianjin, China; Tianjin Lung Cancer Center, Tianjin, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Lung Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China; Key Laboratory of Cancer Prevention and Therapy, Tianjin, China; Tianjin Lung Cancer Center, Tianjin, China.
authors.forename: Shengguang
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Lung Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China; Key Laboratory of Cancer Prevention and Therapy, Tianjin, China; Tianjin Lung Cancer Center, Tianjin, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Lung Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China; Key Laboratory of Cancer Prevention and Therapy, Tianjin, China; Tianjin Lung Cancer Center, Tianjin, China.
authors.forename: Lianmin
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Cancer Prevention and Therapy, Tianjin, China; Department of Gastric Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Ke
authors.affiliation: Department of Lung Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China; Key Laboratory of Cancer Prevention and Therapy, Tianjin, China; Tianjin Lung Cancer Center, Tianjin, China.
authors.forename: Yuesong
authors.initials: Y
authors.lastname: Yin
authors.affiliation: Department of Lung Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China; Key Laboratory of Cancer Prevention and Therapy, Tianjin, China; Tianjin Lung Cancer Center, Tianjin, China; Department of Surgery, Tianjin Beichen Hospital, Tianjin, China.
authors.forename: Haijin
authors.initials: H
authors.lastname: Suo
authors.affiliation: Department of Lung Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China; Key Laboratory of Cancer Prevention and Therapy, Tianjin, China; Tianjin Lung Cancer Center, Tianjin, China.
authors.forename: Bingsheng
authors.initials: B
authors.lastname: Sun
authors.affiliation: Department of Lung Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China; Key Laboratory of Cancer Prevention and Therapy, Tianjin, China; Tianjin Lung Cancer Center, Tianjin, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Lung Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China; Key Laboratory of Cancer Prevention and Therapy, Tianjin, China; Tianjin Lung Cancer Center, Tianjin, China.
authors.forename: Changli
authors.initials: C
authors.lastname: Wang
mesh_terms: D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D018631:ras Proteins / Q000235:genetics
chemical_list: D066246:ErbB Receptors; D011518:Proto-Oncogene Proteins; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D018719:Erb-b2 Receptor Tyrosine Kinases; D018631:ras Proteins; C117307:KRAS protein, human; C512478:EGFR protein, human; C508053:ERBB2 protein, human; C482119:BRAF protein, human