caa a22 4500 605490686 CHVBK 20210128100506.0 cr unu---uuuuu 210128e20151201xx s 000 0 eng 10.1007/s10147-015-0841-4 doi (NATIONALLICENCE)springer-10.1007/s10147-015-0841-4 Gene-expression profiles correlate with the efficacy of anti-EGFR therapy and chemotherapy for colorectal cancer [Elektronische Daten] [Masahiro Inoue, Shin Takahashi, Hiroshi Soeda, Hideki Shimodaira, Mika Watanabe, Koh Miura, Iwao Sasaki, Shunsuke Kato, Chikashi Ishioka] 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. Japan Society of Clinical Oncology, 2015 Colorectal cancer nationallicence Comprehensive gene-expression analysis nationallicence Subtype classification nationallicence Anti-EGFR therapy nationallicence Inoue Masahiro Department of Clinical Oncology, Institute of Development, Aging and Cancer Tohoku University, 4-1 Seiryo-machi, Aobaku, 980-8575, Sendai, Japan aut Takahashi Shin Department of Clinical Oncology, Institute of Development, Aging and Cancer Tohoku University, 4-1 Seiryo-machi, Aobaku, 980-8575, Sendai, Japan aut Soeda Hiroshi Department of Clinical Oncology, Institute of Development, Aging and Cancer Tohoku University, 4-1 Seiryo-machi, Aobaku, 980-8575, Sendai, Japan aut Shimodaira Hideki Department of Clinical Oncology, Institute of Development, Aging and Cancer Tohoku University, 4-1 Seiryo-machi, Aobaku, 980-8575, Sendai, Japan aut Watanabe Mika Department of Pathology, Tohoku University Hospital, 1-1 Seiryo-machi, Aobaku, 980-8575, Sendai, Japan aut Miura Koh Department of Gastroenterological Surgery, Tohoku University Hospital, 1-1 Seiryo-machi, Aobaku, 980-8575, Sendai, Japan aut Sasaki Iwao Department of Gastroenterological Surgery, Tohoku University Hospital, 1-1 Seiryo-machi, Aobaku, 980-8575, Sendai, Japan aut Kato Shunsuke Department of Clinical Oncology, Institute of Development, Aging and Cancer Tohoku University, 4-1 Seiryo-machi, Aobaku, 980-8575, Sendai, Japan aut Ishioka Chikashi Department of Clinical Oncology, Institute of Development, Aging and Cancer Tohoku University, 4-1 Seiryo-machi, Aobaku, 980-8575, Sendai, Japan aut International Journal of Clinical Oncology Springer Japan 20/6(2015-12-01), 1147-1155 1341-9625 20:6<1147 2015 20 10147 https://doi.org/10.1007/s10147-015-0841-4 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s10147-015-0841-4 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Inoue Masahiro Department of Clinical Oncology, Institute of Development, Aging and Cancer Tohoku University, 4-1 Seiryo-machi, Aobaku, 980-8575, Sendai, Japan aut NATIONALLICENCE 700 1- Takahashi Shin Department of Clinical Oncology, Institute of Development, Aging and Cancer Tohoku University, 4-1 Seiryo-machi, Aobaku, 980-8575, Sendai, Japan aut NATIONALLICENCE 700 1- Soeda Hiroshi Department of Clinical Oncology, Institute of Development, Aging and Cancer Tohoku University, 4-1 Seiryo-machi, Aobaku, 980-8575, Sendai, Japan aut NATIONALLICENCE 700 1- Shimodaira Hideki Department of Clinical Oncology, Institute of Development, Aging and Cancer Tohoku University, 4-1 Seiryo-machi, Aobaku, 980-8575, Sendai, Japan aut NATIONALLICENCE 700 1- Watanabe Mika Department of Pathology, Tohoku University Hospital, 1-1 Seiryo-machi, Aobaku, 980-8575, Sendai, Japan aut NATIONALLICENCE 700 1- Miura Koh Department of Gastroenterological Surgery, Tohoku University Hospital, 1-1 Seiryo-machi, Aobaku, 980-8575, Sendai, Japan aut NATIONALLICENCE 700 1- Sasaki Iwao Department of Gastroenterological Surgery, Tohoku University Hospital, 1-1 Seiryo-machi, Aobaku, 980-8575, Sendai, Japan aut NATIONALLICENCE 700 1- Kato Shunsuke Department of Clinical Oncology, Institute of Development, Aging and Cancer Tohoku University, 4-1 Seiryo-machi, Aobaku, 980-8575, Sendai, Japan aut NATIONALLICENCE 700 1- Ishioka Chikashi Department of Clinical Oncology, Institute of Development, Aging and Cancer Tohoku University, 4-1 Seiryo-machi, Aobaku, 980-8575, Sendai, Japan aut NATIONALLICENCE 773 0- International Journal of Clinical Oncology Springer Japan 20/6(2015-12-01), 1147-1155 1341-9625 20:6<1147 2015 20 10147