TY - JOUR
T1 - Gene-expression profiles correlate with the efficacy of anti-EGFR therapy and chemotherapy for colorectal cancer
AU - Inoue, Masahiro
AU - Takahashi, Shin
AU - Soeda, Hiroshi
AU - Shimodaira, Hideki
AU - Watanabe, Mika
AU - Miura, Koh
AU - Sasaki, Iwao
AU - Kato, Shunsuke
AU - Ishioka, Chikashi
N1 - Funding Information:
Dr Ishioka reports receipt of research grants from Chugai, Yakult, Daiichi-Sankyo, and Merk Serono; Dr Kato reports receipt of lecture fees and a research grant from Chugai; Dr Inoue, Dr Takahashi, Dr Soeda, Dr Watanabe, Dr Miura, and Dr Sasaki have no conflict of interest.
Funding Information:
We thank Satoko Aoki for her technical assistance. This work was partially supported by a grant from Project for Development of Innovative Research on Cancer Therapeutics (P-DIRECT).
Publisher Copyright:
© 2015, Japan Society of Clinical Oncology.
PY - 2015/12/1
Y1 - 2015/12/1
N2 - 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.
AB - 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.
KW - Anti-EGFR therapy
KW - Colorectal cancer
KW - Comprehensive gene-expression analysis
KW - Subtype classification
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U2 - 10.1007/s10147-015-0841-4
DO - 10.1007/s10147-015-0841-4
M3 - Article
C2 - 25990448
AN - SCOPUS:84948710716
VL - 20
SP - 1147
EP - 1155
JO - International Journal of Clinical Oncology
JF - International Journal of Clinical Oncology
SN - 1341-9625
IS - 6
ER -