title: Combination of protein coding and noncoding gene expression as a robust prognostic classifier in stage I lung adenocarcinoma.
abstract: Prognostic tests for patients with early-stage lung cancer may provide needed guidance on postoperative surveillance and therapeutic decisions. We used a novel strategy to develop and validate a prognostic classifier for early-stage lung cancer. Specifically, we focused on 42 genes with roles in lung cancer or cancer prognosis. Expression of these biologically relevant genes and their association with relapse-free survival (RFS) were evaluated using microarray data from 148 patients with stage I lung adenocarcinoma. Seven genes associated with RFS were further examined by quantitative reverse transcription PCR in 291 lung adenocarcinoma tissues from Japan, the United States, and Norway. Only BRCA1, HIF1A, DLC1, and XPO1 were each significantly associated with prognosis in the Japan and US/Norway cohorts. A Cox regression-based classifier was developed using these four genes on the Japan cohort and validated in stage I lung adenocarcinoma from the US/Norway cohort and three publicly available lung adenocarcinoma expression profiling datasets. The results suggest that the classifier is robust across ethnically and geographically diverse populations regardless of the technology used to measure gene expression. We evaluated the combination of the four-gene classifier with miRNA miR-21 (MIR21) expression and found that the combination improved associations with prognosis, which were significant in stratified analyses on stage IA and stage IB patients. Thus, the four coding gene classifier, alone or with miR-21 expression, may provide a clinically useful tool to identify high-risk patients and guide recommendations regarding adjuvant therapy and postoperative surveillance of patients with stage I lung adenocarcinoma.
authors: Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA.
authors: Ichiro
authors: I
authors: Akagi
authors: Hirokazu
authors: H
authors: Okayama
authors: Aaron J
authors: AJ
authors: Schetter
authors: Ana I
authors: AI
authors: Robles
authors: Takashi
authors: T
authors: Kohno
authors: Elise D
authors: ED
authors: Bowman
authors: Dickran
authors: D
authors: Kazandjian
authors: Judith A
authors: JA
authors: Welsh
authors: Naohide
authors: N
authors: Oue
authors: Motonobu
authors: M
authors: Saito
authors: Masao
authors: M
authors: Miyashita
authors: Eiji
authors: E
authors: Uchida
authors: Toshihiro
authors: T
authors: Takizawa
authors: Seiichi
authors: S
authors: Takenoshita
authors: Vidar
authors: V
authors: Skaug
authors: Steen
authors: S
authors: Mollerup
authors: Aage
authors: A
authors: Haugen
authors: Jun
authors: J
authors: Yokota
authors: Curtis C
authors: CC
authors: Harris
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019313:BRCA1 Protein / Q000235:genetics / Q000378:metabolism; D018572:Disease-Free Survival; D005260:Female; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D028884:Karyopherins / Q000235:genetics / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques / Q000379:methods; D015999:Multivariate Analysis; D009367:Neoplasm Staging / Q000379:methods; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D060888:Real-Time Polymerase Chain Reaction; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism; D000097606:Exportin 1 Protein
chemical_list: D019313:BRCA1 Protein; D020690:GTPase-Activating Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D028884:Karyopherins; D035683:MicroRNAs; D018160:Receptors, Cytoplasmic and Nuclear; D025521:Tumor Suppressor Proteins; D000097606:Exportin 1 Protein; C492913:BRCA1 protein, human; C112352:DLC1 protein, human; C497442:HIF1A protein, human; C524940:MIRN21 microRNA, human
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