Consensus molecular subtypes classification of colorectal cancer as a predictive factor for chemotherapeutic efficacy against metastatic colorectal cancer

// Akira Okita 1, 2 , Shin Takahashi 1, 2 , Kota Ouchi 1, 2 , Masahiro Inoue 3 , Mika Watanabe 4 , Mareyuki Endo 5 , Hiroshi Honda 6 , Yasuhide Yamada 7, 8 and Chikashi Ishioka 1, 2 1 Department of Clinical Oncology, Institute of Development, Aging and Cancer, Tohoku University, Aoba-ku, Sendai, Japan 2 Department of Medical Oncology, Tohoku University Hospital, Aoba-ku, Sendai, Japan 3 Department of Clinical Oncology, Akita University Graduate School of Medicine, Akita, Japan 4 Department of Pathology, Tohoku University Graduate School of Medicine, Aobaku, Sendai, Japan 5 Department of Pathology, Sendai Kousei Hospital, Aobaku, Sendai, Japan 6 Department of Surgery, Tohoku Rosai Hospital, Aobaku, Sendai, Japan 7 Department of Clinical Oncology, Hamamatsu University School of Medicine, Higashiku, Hamamatsu, Japan 8 Department of Oncology, National Center for Global Health and Medicine, Tokyo, Japan Correspondence to: Chikashi Ishioka, email: chikashi@tohoku.ac.jp Keywords: consensus molecular subtypes; chemotherapeutic efficacy; predictive biomarkers; colorectal cancer; DNA methylation status Received: October 26, 2017 Accepted: February 24, 2018 Published: April 10, 2018 ABSTRACT 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.