Prognostic gene expression signature for squamous cell carcinoma of lung.
OBJECTIVE
This study aimed to identify and validate a gene expression signature for squamous cell carcinoma of the lung (SQCC).


METHODS
A published microarray dataset from 129 SQCC patients was used as a training set to identify the minimal gene set prognostic signature. This was selected using the MAximizing R Square Algorithm (MARSA), a novel heuristic signature optimization procedure based on goodness-of-fit (R square). The signature was tested internally by leave-one-out-cross-validation (LOOCV), and then externally in three independent public lung cancer microarray datasets: two datasets of non-small cell lung cancer (NSCLC) and one of adenocarcinoma (ADC) only. Quantitative-PCR (qPCR) was used to validate the signature in a fourth independent SQCC cohort.


RESULTS
A 12-gene signature that passed the internal LOOCV validation was identified. The signature was independently prognostic for SQCC in two NSCLC datasets (total n = 223) but not in ADC. The lack of prognostic significance in ADC was confirmed in the Director's Challenge ADC dataset (n = 442). The prognostic significance of the signature was validated further by qPCR in another independent cohort containing 62 SQCC samples (hazard ratio, 3.76; 95% confidence interval, 1.10-12.87; P = 0.035).


CONCLUSIONS
We identified a novel 12-gene prognostic signature specific for SQCC and showed the effectiveness of MARSA to identify prognostic gene expression signatures.
Zhu
Chang-Qi
CQ
Ontario Cancer Institute and Princess Margaret Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada. czhu@uhnres.utoronto.ca
Strumpf
Dan
D
Li
Chun-Yan
CY
Li
Qing
Q
Liu
Ni
N
Der
Sandy
S
Shepherd
Frances A
FA
Tsao
Ming-Sound
MS
Jurisica
Igor
I
D000368:Aged; D000465:Algorithms; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015331:Cohort Studies; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction