title: An Expression Signature as an Aid to the Histologic Classification of Non-Small Cell Lung Cancer.
abstract: OBJECTIVE
  Most non-small cell lung cancers (NSCLC) are now diagnosed from small specimens, and classification using standard pathology methods can be difficult. This is of clinical relevance as many therapy regimens and clinical trials are histology dependent. The purpose of this study was to develop an mRNA expression signature as an adjunct test for routine histopathologic classification of NSCLCs.
  
  
  METHODS
  A microarray dataset of resected adenocarcinomas (ADC) and squamous cell carcinomas (SCC) was used as the learning set for an ADC-SCC signature. The Cancer Genome Atlas (TCGA) lung RNAseq dataset was used for validation. Another microarray dataset of ADCs and matched nonmalignant lung was used as the learning set for a tumor versus nonmalignant signature. The classifiers were selected as the most differentially expressed genes and sample classification was determined by a nearest distance approach.
  
  
  RESULTS
  We developed a 62-gene expression signature that contained many genes used in immunostains for NSCLC typing. It includes 42 genes that distinguish ADC from SCC and 20 genes differentiating nonmalignant lung from lung cancer. Testing of the TCGA and other public datasets resulted in high prediction accuracies (93%-95%). In addition, a prediction score was derived that correlates both with histologic grading and prognosis. We developed a practical version of the Classifier using the HTG EdgeSeq nuclease protection-based technology in combination with next-generation sequencing that can be applied to formalin-fixed paraffin-embedded (FFPE) tissues and small biopsies.
  
  
  CONCLUSIONS
  Our RNA classifier provides an objective, quantitative method to aid in the pathologic diagnosis of lung cancer. Clin Cancer Res; 22(19); 4880-9. ©2016 AACR.
authors.affiliation: Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, Texas. Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas. Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: Luc
authors.initials: L
authors.lastname: Girard
authors.affiliation: Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Jaime
authors.initials: J
authors.lastname: Rodriguez-Canales
authors.affiliation: Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Carmen
authors.initials: C
authors.lastname: Behrens
authors.affiliation: HTG Molecular Diagnostics, Tucson, Arizona.
authors.forename: Debrah M
authors.initials: DM
authors.lastname: Thompson
authors.affiliation: HTG Molecular Diagnostics, Tucson, Arizona.
authors.forename: Ihab W
authors.initials: IW
authors.lastname: Botros
authors.affiliation: Department of Clinical Science, University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: Hao
authors.initials: H
authors.lastname: Tang
authors.affiliation: Department of Clinical Science, University of Texas Southwestern Medical Center, Dallas, Texas. Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: Yang
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Department of Thoracic Pathology, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Natasha
authors.initials: N
authors.lastname: Rekhtman
authors.affiliation: Department of Thoracic Pathology, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: William D
authors.initials: WD
authors.lastname: Travis
authors.affiliation: Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, Texas. Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Ignacio I
authors.initials: II
authors.lastname: Wistuba
authors.affiliation: Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, Texas. Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas. Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas. Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: John D
authors.initials: JD
authors.lastname: Minna
authors.affiliation: Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, Texas. Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas. Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas. Adi.Gazdar@UTsouthwestern.edu.
authors.forename: Adi F
authors.initials: AF
authors.lastname: Gazdar
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000145:classification* / Q000235:genetics / Q000473:pathology; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D008175:Lung Neoplasms / Q000145:classification* / Q000235:genetics / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D018426:SEER Program; D059467:Transcriptome
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger