title: A five-gene and corresponding protein signature for stage-I lung adenocarcinoma prognosis.
abstract: OBJECTIVE
  Identification of effective markers for outcome is expected to improve the clinical management of non-small cell lung cancer (NSCLC). Here, we assessed in NSCLC the prognostic efficacy of genes, which we had previously found to be differentially expressed in an in vitro model of human lung carcinogenesis.
  
  
  METHODS
  Prediction algorithms and risk-score models were applied to the expression of the genes in publicly available NSCLC expression data sets. The prognostic capacity of the immunohistochemical expression of proteins encoded by these genes was also tested using formalin-fixed paraffin-embedded (FFPE) tissue specimens from 156 lung adenocarcinomas and 79 squamous cell carcinomas (SCCs).
  
  
  RESULTS
  The survival of all-stages (P < 0.001, HR = 2.0) or stage-I (P < 0.001, HR = 2.84) adenocarcinoma patients that expressed the five-gene in vitro lung carcinogenesis model (FILM) signature was significantly poorer than that of patients who did not. No survival differences were observed between SCCs predicted to express or lack FILM signature. Moreover, all stages (P < 0.001, HR = 1.95) or stage-I (P = 0.001, HR = 2.6) adenocarcinoma patients predicted to be at high risk by FILM transcript exhibited significantly worse survival than patients at low risk. Furthermore, the corresponding protein signature was associated with poor survival (all stages, P < 0.001, HR = 3.6; stage-I, P < 0.001, HR = 3.5; stage-IB, P < 0.001, HR = 4.6) and mortality risk (all stages, P = 0.001, HR = 4.0; stage-I, P = 0.01, HR = 3.4; stage-IB, P < 0.001, HR = 7.2) in lung adenocarcinoma patients.
  
  
  CONCLUSIONS
  Our findings highlight a gene and corresponding protein signature with effective capacity for identification of stage-I lung adenocarcinoma patients with poor prognosis that are likely to benefit from adjuvant therapy.
authors.affiliation: Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Humam
authors.initials: H
authors.lastname: Kadara
authors.forename: Carmen
authors.initials: C
authors.lastname: Behrens
authors.forename: Ping
authors.initials: P
authors.lastname: Yuan
authors.forename: Luisa
authors.initials: L
authors.lastname: Solis
authors.forename: Diane
authors.initials: D
authors.lastname: Liu
authors.forename: Xuemin
authors.initials: X
authors.lastname: Gu
authors.forename: John D
authors.initials: JD
authors.lastname: Minna
authors.forename: J Jack
authors.initials: JJ
authors.lastname: Lee
authors.forename: Edward
authors.initials: E
authors.lastname: Kim
authors.forename: Waun-Ki
authors.initials: WK
authors.lastname: Hong
authors.forename: Ignacio I
authors.initials: II
authors.lastname: Wistuba
authors.forename: Reuben
authors.initials: R
authors.lastname: Lotan
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics; D000077192:Adenocarcinoma of Lung; D000465:Algorithms; D002294:Carcinoma, Squamous Cell / Q000378:metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008175:Lung Neoplasms / Q000235:genetics*; D009367:Neoplasm Staging / Q000379:methods; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D012306:Risk