Consensus Molecular Subtypes Classification of Colorectal Cancer As a Predictive Factor for Chemotherapeutic Efficacy Against Metastatic Colorectal Cancer

Overview

Journal Oncotarget

Specialty Oncology

Date 2018 May 4

PMID 29721154

Citations 91

Authors

Akira Okita

Shin Takahashi

Kota Ouchi

Masahiro Inoue

Mika Watanabe

Mareyuki Endo

Hiroshi Honda

Yasuhide Yamada

Chikashi Ishioka

Affiliations

Soon will be listed here.

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.

Citing Articles

Identifying distinct prognostic and predictive contributions of tumor epithelium versus tumor microenvironment in colorectal cancer.

Yang M, Nebozhyn M, Schell M, Gandhi N, Pflieger L, Loboda A BMC Cancer. 2025; 25(1):441.

PMID: 40075322 PMC: 11899100. DOI: 10.1186/s12885-025-13829-2.

Molecular profiling of risk factors for relapse in Japanese patients with stage II colorectal cancer: a retrospective cohort study.

Kasai S, Kagawa H, Hatakeyama K, Shiomi A, Manabe S, Yamaoka Y Int J Clin Oncol. 2024; 29(12):1887-1895.

PMID: 39287842 DOI: 10.1007/s10147-024-02626-9.

Consensus molecular subtyping of metastatic colorectal cancer expands biomarker-directed therapeutic benefit for patients with CMS1 and CMS2 tumors.

Chowdhury S, Xiu J, Ribeiro J, Nicolaides T, Zhang J, Korn W Br J Cancer. 2024; 131(8):1328-1339.

PMID: 39227409 PMC: 11473766. DOI: 10.1038/s41416-024-02826-0.

Differential expression of angiogenesis-related genes 'VEGF' and 'angiopoietin-1' in metastatic and EMAST-positive colorectal cancer patients.

Torshizi Esfahani A, Mohammadpour S, Jalali P, Yaghoobi A, Karimpour R, Torkamani S Sci Rep. 2024; 14(1):10539.

PMID: 38719941 PMC: 11079037. DOI: 10.1038/s41598-024-61000-x.

Combination of bazedoxifene with chemotherapy and SMAC-mimetics for the treatment of colorectal cancer.

Dmello R, Palmieri M, Thilakasiri P, Doughty L, Nero T, Poh A Cell Death Dis. 2024; 15(4):255.

PMID: 38600086 PMC: 11006905. DOI: 10.1038/s41419-024-06631-8.

References

Capello M, Lee M, Wang H, Babel I, Katz M, Fleming J . Carboxylesterase 2 as a Determinant of Response to Irinotecan and Neoadjuvant FOLFIRINOX Therapy in Pancreatic Ductal Adenocarcinoma. J Natl Cancer Inst. 2015; 107(8). PMC: 4554193. DOI: 10.1093/jnci/djv132. View

Schlicker A, Beran G, Chresta C, McWalter G, Pritchard A, Weston S . Subtypes of primary colorectal tumors correlate with response to targeted treatment in colorectal cell lines. BMC Med Genomics. 2013; 5:66. PMC: 3543849. DOI: 10.1186/1755-8794-5-66. View

Zhang X, Shimodaira H, Soeda H, Komine K, Takahashi H, Ouchi K . CpG island methylator phenotype is associated with the efficacy of sequential oxaliplatin- and irinotecan-based chemotherapy and EGFR-related gene mutation in Japanese patients with metastatic colorectal cancer. Int J Clin Oncol. 2016; 21(6):1091-1101. DOI: 10.1007/s10147-016-1017-6. View

Fitzmaurice C, Allen C, Barber R, Barregard L, Bhutta Z, Brenner H . Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life-years for 32 Cancer Groups, 1990 to 2015: A Systematic Analysis for the Global Burden of Disease Study. JAMA Oncol. 2016; 3(4):524-548. PMC: 6103527. DOI: 10.1001/jamaoncol.2016.5688. View

Lenz H, Ou F, Venook A, Hochster H, Niedzwiecki D, Goldberg R . Impact of Consensus Molecular Subtype on Survival in Patients With Metastatic Colorectal Cancer: Results From CALGB/SWOG 80405 (Alliance). J Clin Oncol. 2019; 37(22):1876-1885. PMC: 6675593. DOI: 10.1200/JCO.18.02258. View

Tournigand C, Andre T, Achille E, Lledo G, Flesh M, Mery-Mignard D . FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: a randomized GERCOR study. J Clin Oncol. 2003; 22(2):229-37. DOI: 10.1200/JCO.2004.05.113. View

Cremolini C, Loupakis F, Antoniotti C, Lupi C, Sensi E, Lonardi S . FOLFOXIRI plus bevacizumab versus FOLFIRI plus bevacizumab as first-line treatment of patients with metastatic colorectal cancer: updated overall survival and molecular subgroup analyses of the open-label, phase 3 TRIBE study. Lancet Oncol. 2015; 16(13):1306-15. DOI: 10.1016/S1470-2045(15)00122-9. View

Tuy H, Shiomi H, Mukaisho K, Naka S, Shimizu T, Sonoda H . ABCG2 expression in colorectal adenocarcinomas may predict resistance to irinotecan. Oncol Lett. 2016; 12(4):2752-2760. PMC: 5038226. DOI: 10.3892/ol.2016.4937. View

Simmonds P . Palliative chemotherapy for advanced colorectal cancer: systematic review and meta-analysis. Colorectal Cancer Collaborative Group. BMJ. 2000; 321(7260):531-5. PMC: 27466. DOI: 10.1136/bmj.321.7260.531. View

10.

Therasse P, Arbuck S, Eisenhauer E, Wanders J, Kaplan R, Rubinstein L . New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000; 92(3):205-16. DOI: 10.1093/jnci/92.3.205. View

11.

Inoue M, Takahashi S, Soeda H, Shimodaira H, Watanabe M, Miura K . Gene-expression profiles correlate with the efficacy of anti-EGFR therapy and chemotherapy for colorectal cancer. Int J Clin Oncol. 2015; 20(6):1147-55. DOI: 10.1007/s10147-015-0841-4. View

12.

Douillard J, Oliner K, Siena S, Tabernero J, Burkes R, Barugel M . Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer. N Engl J Med. 2013; 369(11):1023-34. DOI: 10.1056/NEJMoa1305275. View

13.

Tournigand C, Cervantes A, Figer A, Lledo G, Flesch M, Buyse M . OPTIMOX1: a randomized study of FOLFOX4 or FOLFOX7 with oxaliplatin in a stop-and-Go fashion in advanced colorectal cancer--a GERCOR study. J Clin Oncol. 2006; 24(3):394-400. DOI: 10.1200/JCO.2005.03.0106. View

14.

Marisa L, De Reynies A, Duval A, Selves J, Gaub M, Vescovo L . Gene expression classification of colon cancer into molecular subtypes: characterization, validation, and prognostic value. PLoS Med. 2013; 10(5):e1001453. PMC: 3660251. DOI: 10.1371/journal.pmed.1001453. View

15.

Guinney J, Dienstmann R, Wang X, De Reynies A, Schlicker A, Soneson C . The consensus molecular subtypes of colorectal cancer. Nat Med. 2015; 21(11):1350-6. PMC: 4636487. DOI: 10.1038/nm.3967. View

16.

Karapetis C, Khambata-Ford S, Jonker D, OCallaghan C, Tu D, Tebbutt N . K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N Engl J Med. 2008; 359(17):1757-65. DOI: 10.1056/NEJMoa0804385. View

17.

Nygard S, Vainer B, Nielsen S, Bosman F, Tejpar S, Roth A . DNA Topoisomerase I Gene Copy Number and mRNA Expression Assessed as Predictive Biomarkers for Adjuvant Irinotecan in Stage II/III Colon Cancer. Clin Cancer Res. 2015; 22(7):1621-31. DOI: 10.1158/1078-0432.CCR-15-0561. View

18.

Arnold D, Lueza B, Douillard J, Peeters M, Lenz H, Venook A . Prognostic and predictive value of primary tumour side in patients with RAS wild-type metastatic colorectal cancer treated with chemotherapy and EGFR directed antibodies in six randomized trials. Ann Oncol. 2017; 28(8):1713-1729. PMC: 6246616. DOI: 10.1093/annonc/mdx175. View

19.

Uchida K, Otake K, Tanaka K, Hashimoto K, Saigusa S, Matsushita K . Clinical implications of CES2 RNA expression in neuroblastoma. J Pediatr Surg. 2013; 48(3):502-9. DOI: 10.1016/j.jpedsurg.2012.10.004. View

20.

Yamada Y, Denda T, Gamoh M, Iwanaga I, Yuki S, Shimodaira H . S-1 and irinotecan plus bevacizumab versus mFOLFOX6 or CapeOX plus bevacizumab as first-line treatment in patients with metastatic colorectal cancer (TRICOLORE): a randomized, open-label, phase III, noninferiority trial. Ann Oncol. 2018; 29(3):624-631. PMC: 5889030. DOI: 10.1093/annonc/mdx816. View