Proteomic signature corresponding to the response to gefitinib (Iressa, ZD1839), an epidermal growth factor receptor tyrosine kinase inhibitor in lung adenocarcinoma.
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.
Okano
Tetsuya
T
Proteome Bioinformatics Project, National Cancer Center Research Institute, Department of Surgery, Tokyo Medical University, and Clinical Laboratory Division, National Cancer Center Hospital, Japan.
Kondo
Tadashi
T
Fujii
Kiyonaga
K
Nishimura
Toshihide
T
Takano
Toshimi
T
Ohe
Yuichiro
Y
Tsuta
Koji
K
Matsuno
Yoshihiro
Y
Gemma
Akihiko
A
Kato
Harbumi
H
Kudoh
Shoji
S
Hirohashi
Setsuo
S
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*
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