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

Oncology. 2017;93(2):127-135. doi: 10.1159/000464329. Epub 2017 May 17.

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.

Keywords: Chemotherapy; Gastric cancer; Microarray.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Aged
  • Antimetabolites, Antineoplastic / administration & dosage
  • Antimetabolites, Antineoplastic / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols*
  • Cisplatin / administration & dosage
  • Cisplatin / 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
  • Oxonic Acid / therapeutic use*
  • Prognosis
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / pathology
  • Survival Analysis
  • Taxoids / administration & dosage
  • Taxoids / therapeutic use*
  • Tegafur / administration & dosage
  • Tegafur / therapeutic use*
  • Treatment Outcome

Substances

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