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. 2018 Apr 10;9(27):18698-18711.
doi: 10.18632/oncotarget.24617.

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 , Chikashi Ishioka  1   2
Affiliations

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

Akira Okita et al. Oncotarget. .

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.

Keywords: DNA methylation status; chemotherapeutic efficacy; colorectal cancer; consensus molecular subtypes; predictive biomarkers.

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Conflict of interest statement

CONFLICTS OF INTEREST Prof. Ishioka reported grants from the Japan Agency for Medical Research and Development; the Ministry of Education, Culture Sports, Science, and Technology of Japan, during the conduct of the study; grants and personal fees from Mochida, Chugai, Novartis, Merck-Serono, Daiichi-Sankyo, Takeda, Nihon-Kayaku, Yakult, Taiho, Ono and Asahikasei-Pharma; personal fees from Eli Lilly and Bayer; and grants from Kyowa-Kirin, Eizai, Tsumura, Astellas, Kissei and Bristol, outside the submitted work. Dr. Takahashi reported grants from The Ministry of Education, Culture Sports, Science, and Technology of Jaman during the conduct of the study; grants and personal fees from Merck-Serono and Taiho Pharmaceutical; and personal fees from Asahi Kasei, Daiichi Sankyo, Medicon, Novartis, and Mochida Pharmaceutical, outside the submitted work. None of the remaining authors have any conflicts of interest to declare.

Figures

Figure 1
Figure 1. Kaplan–Meier survival curves for PFS and OS in the IRI- (dotted line) and OX-based groups (solid line)
(A) PFS; (B) OS Abbreviations: IRI, irinotecan; OX, oxaliplatin; PFS, progression-free survival; CI, confidence interval; HR, hazard ratio.
Figure 2
Figure 2. Subgroup analysis based on consensus molecular subtypes
Abbreviations: IRI, irinotecan; OX, oxaliplatin; OS, overall survival; CI, confidence interval; HR, hazard ratio.
Figure 3
Figure 3. Box-and-whisker plots of the gene expression levels for TOP1 and CES2
Figure 4
Figure 4. Kaplan–Meier survival curves of anti-EGFR therapy in CMS1 (orange line), CMS2 (blue line), CMS3 (pink line), and CMS4 (green line)
(A) Progression-free survival time; (B) Overall survival time Abbreviations: PFS, progression-free survival; OS, overall survival; CI, confidence interval; HR, hazard ratio.
See this image and copyright information in PMC

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