Robust gene expression signature from formalin-fixed paraffin-embedded samples predicts prognosis of non–small-cell lung cancer patients

Y Xie, G Xiao, KR Coombes, C Behrens, LM Solis… - Clinical cancer …, 2011 - AACR
Y Xie, G Xiao, KR Coombes, C Behrens, LM Solis, G Raso, L Girard, HS Erickson, J Roth
Clinical cancer research, 2011AACR
Purpose: The requirement of frozen tissues for microarray experiments limits the clinical
usage of genome-wide expression profiling by using microarray technology. The goal of this
study is to test the feasibility of developing lung cancer prognosis gene signatures by using
genome-wide expression profiling of formalin-fixed paraffin-embedded (FFPE) samples,
which are widely available and provide a valuable rich source for studying the association of
molecular changes in cancer and associated clinical outcomes. Experimental Design: We …
Abstract
Purpose: The requirement of frozen tissues for microarray experiments limits the clinical usage of genome-wide expression profiling by using microarray technology. The goal of this study is to test the feasibility of developing lung cancer prognosis gene signatures by using genome-wide expression profiling of formalin-fixed paraffin-embedded (FFPE) samples, which are widely available and provide a valuable rich source for studying the association of molecular changes in cancer and associated clinical outcomes.
Experimental Design: We randomly selected 100 Non–Small-Cell lung cancer (NSCLC) FFPE samples with annotated clinical information from the UT-Lung SPORE Tissue Bank. We microdissected tumor area from FFPE specimens and used Affymetrix U133 plus 2.0 arrays to attain gene expression data. After strict quality control and analysis procedures, a supervised principal component analysis was used to develop a robust prognosis signature for NSCLC. Three independent published microarray datasets were used to validate the prognosis model.
Results: This study showed that the robust gene signature derived from genome-wide expression profiling of FFPE samples is strongly associated with lung cancer clinical outcomes and can be used to refine the prognosis for stage I lung cancer patients, and the prognostic signature is independent of clinical variables. This signature was validated in several independent studies and was refined to a 59-gene lung cancer prognosis signature.
Conclusions: We conclude that genome-wide profiling of FFPE lung cancer samples can identify a set of genes whose expression level provides prognostic information across different platforms and studies, which will allow its application in clinical settings. Clin Cancer Res; 17(17); 5705–14. ©2011 AACR.
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