Gene expression signature predicts recurrence in lung adenocarcinoma.
OBJECTIVE
Improving outcomes for early-stage lung cancer is a major research focus at present because a significant proportion of stage I patients develop recurrent disease within 5 years of curative-intent lung resection. Within tumor stage groups, conventional prognostic indicators currently fail to predict relapse accurately.


METHODS
To identify a gene signature predictive of recurrence in primary lung adenocarcinoma, we analyzed gene expression profiles in a training set of 48 node-negative tumors (stage I-II), comparing tumors from cases who remained disease-free for a minimum of 36 months with those from cases whose disease recurred within 18 months of complete resection.


RESULTS
Cox proportional hazards modeling with leave-one-out cross-validation identified a 54-gene signature capable of predicting risk of recurrence in two independent validation cohorts of 55 adenocarcinomas [log-rank P=0.039; hazard ratio (HR), 2.2; 95% confidence interval (95% CI), 1.1-4.7] and 40 adenocarcinomas (log-rank P=0.044; HR, 3.3; 95% CI, 1.4-7.9). Kaplan-Meier log-rank analysis found that predicted poor-outcome groups had significantly shorter survival, and furthermore, the signature predicted outcome independently of conventional indicators of tumor stage and node stage. In a subset of earliest stage adenocarcinomas, generally expected to have good outcome, the signature predicted samples with significantly poorer survival.


CONCLUSIONS
We describe a 54-gene signature that predicts the risk of recurrent disease independently of tumor stage and which therefore has potential to refine clinical prognosis for patients undergoing resection for primary adenocarcinoma of the lung.
Larsen
Jill E
JE
Department of Thoracic Medicine, The Prince Charles Hospital, Brisbane, Australia. Jill_E_Larsen@health.qld.gov.au
Pavey
Sandra J
SJ
Passmore
Linda H
LH
Bowman
Rayleen V
RV
Hayward
Nicholas K
NK
Fong
Kwun M
KM
D000230:Adenocarcinoma / Q000473:pathology*; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D052138:Genes, Neoplasm; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis*; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D012306:Risk
D014408:Biomarkers, Tumor