title: Proteomic signature corresponding to the response to gefitinib (Iressa, ZD1839), an epidermal growth factor receptor tyrosine kinase inhibitor in lung adenocarcinoma.
abstract: OBJECTIVE
  We aimed to identify candidate proteins for tumor markers to predict the response to gefitinib treatment.
  
  
  METHODS
  We did two-dimensional difference gel electrophoresis to create the protein expression profile of lung adenocarcinoma tissues from patients who showed a different response to gefitinib treatment. We used a support vector machine algorithm to select the proteins that best distinguished 31 responders from 16 nonresponders. The prediction performance of the selected spots was validated by an external sample set, including six responders and eight nonresponders. The results were validated using specific antibodies.
  
  
  RESULTS
  We selected nine proteins that distinguish responders from nonresponders. The predictive performance of the nine proteins was validated examining an additional six responders and eight nonresponders, resulting in positive and negative predictive values of 100% (six of six) and 87.5% (seven of eight), respectively. The differential expression of one of the nine proteins, heart-type fatty acid-binding protein, was successfully validated by ELISA. We also identified 12 proteins as a signature to distinguish tumors based on their epidermal growth factor receptor gene mutation status.
  
  
  CONCLUSIONS
  Study of these proteins may contribute to the development of personalized therapy for lung cancer patients.
authors.affiliation: Proteome Bioinformatics Project, National Cancer Center Research Institute, Department of Surgery, Tokyo Medical University, and Clinical Laboratory Division, National Cancer Center Hospital, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Okano
authors.forename: Tadashi
authors.initials: T
authors.lastname: Kondo
authors.forename: Kiyonaga
authors.initials: K
authors.lastname: Fujii
authors.forename: Toshihide
authors.initials: T
authors.lastname: Nishimura
authors.forename: Toshimi
authors.initials: T
authors.lastname: Takano
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Ohe
authors.forename: Koji
authors.initials: K
authors.lastname: Tsuta
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Matsuno
authors.forename: Akihiko
authors.initials: A
authors.lastname: Gemma
authors.forename: Harbumi
authors.initials: H
authors.lastname: Kato
authors.forename: Shoji
authors.initials: S
authors.lastname: Kudoh
authors.forename: Setsuo
authors.initials: S
authors.lastname: Hirohashi
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism*; D000368:Aged; D000465:Algorithms; D019008:Drug Resistance, Neoplasm; D015180:Electrophoresis, Gel, Two-Dimensional; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D000074026:Fatty Acid Binding Protein 3; D050556:Fatty Acid-Binding Proteins / Q000378:metabolism; D005260:Female; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D040901:Proteomics / Q000379:methods*; D011799:Quinazolines / Q000494:pharmacology*
chemical_list: C493408:FABP3 protein, human; D000074026:Fatty Acid Binding Protein 3; D050556:Fatty Acid-Binding Proteins; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D066246:ErbB Receptors; D000077156:Gefitinib