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マイクロアレイを用いた切除不能進行胃癌におけるS-1,シスプラチン,ドセタキセル3剤併用化学療法の治療効果予測因子についての検討

Authors :
Kitamura, Shinji
Tanahashi, Toshihito
Aoyagi, Eriko
Nakagawa, Tadahiko
Okamoto, Koichi
Kimura, Tetsuo
Miyamoto, Hiroshi
Mitsui, Yasuhiro
Rokutan, Kazuhito
Muguruma, Naoki
Takayama, Tetsuji
Source :
Oncology. 93(2):127-135
Publication Year :
2017
Publisher :
Karger, 2017.

Abstract

Objectives: The aim of this study was to identify biomarkers for predicting the efficacy of docetaxel, cisplatin, and S-1 (DCS) therapy for advanced gastric cancer using microarrays of biopsy specimens before chemotherapy. Methods: Nineteen samples were taken from 19 patients with unresectable metastatic gastric cancer who received DCS as a first-line therapy. Laser capture microdissection was performed, and total cellular RNA was extracted from each microdissected sample. Whole-gene expression was analyzed by microarray, and the difference in mRNA expression observed with the microarrays was confirmed by quantitative real-time PCR. Immunohistochemical staining was performed using clinical tissue sections obtained by endoscopic biopsy. Results: Eleven patients were identified as early responders and 8 patients as nonresponders to DCS therapy. Twenty-nine genes showed significant differences in relative expression ratios between tumor and normal tissues. A classifier set of 29 genes had high accuracy (94.7%) for distinguishing gene expression between 11 early responders and 8 nonresponders. Decreasing the size of the classifier set to 4 genes (PDGFB, PCGF3, CISH, and ANXA5) increased the accuracy to 100%. Expression levels by real-time PCR for validation were well correlated with those 4 genes in microarrays. Conclusion: The genes identified may serve as efficient biomarkers for personalized cancer-targeted therapy.

Details

Language :
English
ISSN :
00302414
Volume :
93
Issue :
2
Database :
OpenAIRE
Journal :
Oncology
Accession number :
edsair.jairo.........799a668b7bbe6d40e8147f6ca6b9c46b