Gene-expression profiles correlate with the efficacy of anti-EGFR therapy and chemotherapy for colorectal cancer

Masahiro Inoue, Shin Takahashi, Hiroshi Soeda, Hideki Shimodaira, Mika Watanabe, Koh Miura, Iwao Sasaki, Shunsuke Kato, Chikashi Ishioka

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

Background: Comprehensive gene-expression analysis is very useful for classifying specific cancers into subgroups on the basis of their biological characteristics; it is used both prognostically and predictively. The purpose of this study was to classify unresectable advanced or recurrent colorectal cancer (CRC) by gene-expression profiling of formalin-fixed paraffin-embedded tissues and to correlate CRC subgroups with clinicopathological and molecular features and clinical outcomes. Methods: One hundred patients with advanced or recurrent CRC were enrolled. RNA extracted from FFPE tissues was subjected to gene-expression microarray analysis. Results: The patients were stratified into four subgroups (subtypes A1, A2, B1, and B2) by unsupervised hierarchical clustering. By use of principle-components analysis (PCA), the patients were divided into subtypes A and B on the basis of component 1 and into subtypes 1 and 2 on the basis of component 2. Subtype A was significantly enriched among patients without the KRAS mutation and with an earlier clinical stage at diagnosis. With regard to anti-EGFR therapy, progression-free survival (PFS) was better for patients in subtype A without the KRAS mutation than for those with the KRAS mutation (P = 0.047). PFS for patients without the KRAS mutation in subtype B was comparable with that for patients with the KRAS mutation (P = 0.55). Similar results were observed in a validation set. Conclusion: We found that gene-expression profiles enabled stratification of CRC patients into four subgroups. The efficacy of anti-EGFR therapy was correlated with component 1 from PCA. This comprehensive study may explain the heterogeneity of unresectable advanced or recurrent CRC and could be useful for identifying novel biomarkers for CRC treatment.

Original languageEnglish
Pages (from-to)1147-1155
Number of pages9
JournalInternational Journal of Clinical Oncology
Volume20
Issue number6
DOIs
Publication statusPublished - 2015 Dec 1

Keywords

  • Anti-EGFR therapy
  • Colorectal cancer
  • Comprehensive gene-expression analysis
  • Subtype classification

ASJC Scopus subject areas

  • Surgery
  • Hematology
  • Oncology

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