（癌学会受賞講演の内容についての論文 Human Cancer Biology の抜粋）

Title :

Proteomic Signature Corresponding to the Response to Gefitinib（Iressa, ZD1839）, an Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor in Lung Adenocarcinoma Tetsuya Okano, 1, 6 Tadashi Kondo, 1 Kiyonaga Fujii, 2 Toshihide Nishimura, 2 Toshimi Takano, 4 Yuichiro Ohe, 4 Koji Tsuta, 5 Yoshihiro Matsuno, 5 Akihiko Gemma, 6 Harbumi Kato, 2, 3 Shoji Kudoh, 6 and Setsuo Hirohashi 1

Abstract Purpose :

We aimed to identify candidate proteins for tumor markers to predict the response to gefitinib treatment.

Experimental Design : 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 vectormachine 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, hearttype 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.

Materials and Methods :

Protein extraction and protein expression profiling. The frozen tumor tissues were crushed to frozen powder with a Multi-Beads Shocker（Yasui-kikai, Osaka, Japan） under cooling with liquid nitrogen. The frozen powder was then treated with urea lysis buffer （7 mol/L urea, 2 mol/L thiourea, 3% CHAPS, 1% Triton X-100） for 30 min on ice. After centrifugation at 15,000 rpm for 30 min, the supernatant was recovered as cellular protein for the protein expression study.

参考文献：Clin Cancer Res 2007;13（3） February 1, 2007