title: Robust gene expression signature from formalin-fixed paraffin-embedded samples predicts prognosis of non-small-cell lung cancer patients.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
authors: Department of Clinical Sciences, Simmons Cancer Center, Internal Medicine, Pharmacology, and Hamon Center for Therapeutic Oncology Research, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors: Yang
authors: Y
authors: Xie
authors: Guanghua
authors: G
authors: Xiao
authors: Kevin R
authors: KR
authors: Coombes
authors: Carmen
authors: C
authors: Behrens
authors: Luisa M
authors: LM
authors: Solis
authors: Gabriela
authors: G
authors: Raso
authors: Luc
authors: L
authors: Girard
authors: Heidi S
authors: HS
authors: Erickson
authors: Jack
authors: J
authors: Roth
authors: John V
authors: JV
authors: Heymach
authors: Cesar
authors: C
authors: Moran
authors: Kathy
authors: K
authors: Danenberg
authors: John D
authors: JD
authors: Minna
authors: Ignacio I
authors: II
authors: Wistuba
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality; D005260:Female; D005557:Formaldehyde; D020869:Gene Expression Profiling; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D016612:Paraffin Embedding; D011379:Prognosis; D016707:Tissue Fixation
chemical_list: D005557:Formaldehyde