Response Predictors of S-1, Cisplatin, and Docetaxel Combination Chemotherapy for Metastatic Gastric Cancer: Microarray Analysis of Whole Human Genes.

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.

• Authors: Shinji Kitamura, Toshihito Tanahashi, Eriko Aoyagi, Tadahiko Nakagawa, Koichi Okamoto, Tetsuo Kimura, Hiroshi Miyamoto, Yasuhiro Mitsui, Kazuhito Rokutan, Naoki Muguruma, Tetsuji Takayama
• Journal: Oncology (Oncology) Vol. 93 Issue 2 Pg. 127-135 ( 2017) ISSN: 1423-0232 [Electronic] Switzerland
• PMID: 28511180 (Publication Type: Clinical Trial, Journal Article)
• Copyright: © 2017 S. Karger AG, Basel.

Chemical References

• Antimetabolites, Antineoplastic
• Drug Combinations
• Taxoids
• S 1 (combination)
• Tegafur
• Docetaxel
• Oxonic Acid
• Cisplatin

Topics

• Adult
• Aged
• Antimetabolites, Antineoplastic (administration & dosage, therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols
• Cisplatin (administration & dosage, therapeutic use)
• Docetaxel
• Dose-Response Relationship, Drug
• Drug Combinations
• Female
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Male
• Microarray Analysis
• Middle Aged
• Molecular Targeted Therapy
• Neoplasm Metastasis
• Oxonic Acid (administration & dosage, therapeutic use)
• Prognosis
• Stomach Neoplasms (drug therapy, genetics, pathology)
• Survival Analysis
• Taxoids (administration & dosage, therapeutic use)
• Tegafur (administration & dosage, therapeutic use)
• Treatment Outcome