ArticleInternational journal of clinical oncology2016
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.
Article in International journal of clinical oncology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.
- Global differences in the prevalence of the CpG island methylator phenotype of colorectal cancer.BMC cancer · 2019Pooled it
- Review
- Genome-wide DNA methylation status is a predictor of the efficacy of anti-EGFR antibodies in the second-line treatment of metastatic colorectal cancer: Translational research of the EPIC trial.International journal of colorectal disease · 2024Article
- The CpG Island Methylator Phenotype Status in Synchronous and Solitary Primary Colorectal Cancers: Prognosis and Effective Therapeutic Drug Prediction.International journal of molecular sciences · 2024Review
- A Multi-Omics Overview of Colorectal Cancer to Address Mechanisms of Disease, Metastasis, Patient Disparities and Outcomes.Cancers · 2023Review
- Epigenome-Wide DNA Methylation Profiling in Colorectal Cancer and Normal Adjacent Colon Using Infinium Human Methylation 450K.Diagnostics (Basel, Switzerland) · 2022Article
- Epigenetic Alterations Upstream and Downstream of p53 Signaling in Colorectal Carcinoma.Cancers · 2021Review
- Advances in CpG Island Methylator Phenotype Colorectal Cancer Therapies.Frontiers in oncology · 2021Review
- The transition from primary colorectal cancer to isolated peritoneal malignancy is associated with an increased tumour mutational burden.Scientific reports · 2020Article
- The role ofBMC cancer · 2019Article
- Association of CHFR Promoter Methylation with Treatment Outcomes of Irinotecan-Based Chemotherapy in Metastatic Colorectal Cancer.Neoplasia (New York, N.Y.) · 2019Article
- Clinical, Pathological, and Molecular Characteristics of CpG Island Methylator Phenotype in Colorectal Cancer: A Systematic Review and Meta-analysis.Translational oncology · 2018Article
- Article
- Distinct clinical outcomes of two CIMP-positive colorectal cancer subtypes based on a revised CIMP classification system.British journal of cancer · 2017Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe CpG island methylator phenotype (CIMP) with multiple promoter methylated loci has been observed in a subset of human colorectal cancer (CRC) cases. CIMP status, which is closely associated with specific clinicopathological and molecular characteristics, is considered a potential predictive biomarker for efficacy of cancer treatment. However, the relationship between the effect of standard chemotherapy, including cytotoxic drugs and anti-epidermal growth factor receptor (EGFR) antibodies, and CIMP status has not been elucidated.
methodsIn 125 metastatic colorectal cancer (mCRC) patients, we investigated how clinical outcome of chemotherapy was related to CIMP status as detected by methylation-specific PCR (MSP) and to genetic status in five EGFR-related genes (KRAS, BRAF, PIK3CA, NRAS, and AKT1) as detected by direct sequencing.
resultsCIMP-positive status was significantly associated with proximal tumor location and peritoneum metastasis (all P values <0.05). The progression-free survival of patients with CIMP-positive tumors receiving sequential therapy with FOLFOX as the first-line treatment followed by irinotecan-based therapy as the second-line treatment (median = 6.6 months) was inferior to that of such patients receiving the reverse sequence (median = 15.2 months; P = 0.043). Furthermore, CIMP-positive tumors showed higher mutation frequencies for the five EGFR-related genes (74.1 %) than the CIMP-negative tumors did (50.0 %). Among the KRAS wild-type tumors, CIMP-positive tumors were associated with a worse clinical outcome than CIMP-negative tumors following anti-EGFR antibody therapy.
conclusionSequential FOLFOX followed by an irinotecan-based regimen is unfavorable in patients with CIMP-positive tumors. High frequencies of mutation in EGFR-related genes in CIMP-positive tumors may cause the lower response to anti-EGFR antibody therapy seen in patients with wild-type KRAS and CIMP-positive tumors.
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