TY - JOUR
T1 - Consensus molecular subtypes classification of colorectal cancer as a predictive factor for chemotherapeutic efficacy against metastatic colorectal cancer
AU - Okita, Akira
AU - Takahashi, Shin
AU - Ouchi, Kota
AU - Inoue, Masahiro
AU - Watanabe, Mika
AU - Endo, Mareyuki
AU - Honda, Hiroshi
AU - Yamada, Yasuhide
AU - Ishioka, Chikashi
N1 - Funding Information:
Dr. Okita is a postgraduate student of the Medical Oncologist Course, Tohoku Cancer Professional Training Promotion Plan. We thank our patients and medical and technical staff, particularly Ms. Hiromi Nakano. We also thank Enago (www.enago.jp) for the English language review. This study was supported by a grant from the Project for Development of Innovative Research on Cancer Therapeutics (P-DIRECT) and the Project for Cancer Research and Therapeutic Evolution (P-CREATE) by the Japan Agency for Medical Research and Development. This study was also supported by a grant from the Japan Society for the Promotion of Science (JSPS), Grant Number 15H04307 and 22700902, by the Ministry of Education, Culture, Sports, Science, and Technology of Japan.
Publisher Copyright:
© Okita et al.
PY - 2018/4/10
Y1 - 2018/4/10
N2 - The consensus molecular subtypes (CMS) classification is one of the most robust colorectal cancer (CRC) classifications based on comprehensive gene expression profiles. This study aimed to clarify whether the CMS is a predictive factor for therapeutic effects of standard chemotherapies for metastatic CRC (mCRC). We retrospectively enrolled 193 patients with mCRCs, and using comprehensive gene expression data, classified them into 4 subtypes: CMS1-CMS4. The associations between the subtypes and treatment outcomes were analyzed. Regarding first-line chemotherapy, irinotecan (IRI)-based chemotherapy was significantly superior to oxaliplatin (OX)-based chemotherapy for progression-free survival (PFS; hazard ratio [HR] = 0.31, 95% confidence interval [CI] 0.13-0.64) and overall survival (OS; HR = 0.45, 95% CI 0.19-0.99) in CMS4. Regarding the anti-epidermal growth factor receptor (anti-EGFR) therapy, CMS1 showed particularly worse PFS (HR = 2.50, 95% CI 1.31-4.39) and OS (HR = 4.23, 95% CI 1.83-9.04), and CMS2 showed particularly good PFS (HR = 0.67, 95% CI 0.44-1.01) and OS (HR = 0.49, 95% CI 0.27-0.87) compared with the other subtypes. The biological characteristics of CMS may influence the efficacy of chemotherapy. CMS might be a new predictive factor for the efficacy of chemotherapy against mCRCs.
AB - The consensus molecular subtypes (CMS) classification is one of the most robust colorectal cancer (CRC) classifications based on comprehensive gene expression profiles. This study aimed to clarify whether the CMS is a predictive factor for therapeutic effects of standard chemotherapies for metastatic CRC (mCRC). We retrospectively enrolled 193 patients with mCRCs, and using comprehensive gene expression data, classified them into 4 subtypes: CMS1-CMS4. The associations between the subtypes and treatment outcomes were analyzed. Regarding first-line chemotherapy, irinotecan (IRI)-based chemotherapy was significantly superior to oxaliplatin (OX)-based chemotherapy for progression-free survival (PFS; hazard ratio [HR] = 0.31, 95% confidence interval [CI] 0.13-0.64) and overall survival (OS; HR = 0.45, 95% CI 0.19-0.99) in CMS4. Regarding the anti-epidermal growth factor receptor (anti-EGFR) therapy, CMS1 showed particularly worse PFS (HR = 2.50, 95% CI 1.31-4.39) and OS (HR = 4.23, 95% CI 1.83-9.04), and CMS2 showed particularly good PFS (HR = 0.67, 95% CI 0.44-1.01) and OS (HR = 0.49, 95% CI 0.27-0.87) compared with the other subtypes. The biological characteristics of CMS may influence the efficacy of chemotherapy. CMS might be a new predictive factor for the efficacy of chemotherapy against mCRCs.
KW - Chemotherapeutic efficacy
KW - Colorectal cancer
KW - Consensus molecular subtypes
KW - DNA methylation status
KW - Predictive biomarkers
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U2 - 10.18632/oncotarget.24617
DO - 10.18632/oncotarget.24617
M3 - Article
C2 - 29721154
AN - SCOPUS:85045212273
SN - 1949-2553
VL - 9
SP - 18698
EP - 18711
JO - Oncotarget
JF - Oncotarget
IS - 27
ER -
