DNA methylation status as a biomarker of anti‐epidermal growth factor receptor treatment for metastatic colorectal cancer

Anti‐epidermal growth factor receptor (EGFR) treatment is an effective option for metastatic colorectal cancer (CRC) treatment. However, there are few reliable biomarkers to predict the clinical response to anti‐EGFR treatment. We investigated the genome‐wide DNA methylation status in metastatic col...

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Bibliographic Details
Published in:Cancer science 2015-12, Vol.106 (12), p.1722-1729
Main Authors: Ouchi, Kota, Takahashi, Shin, Yamada, Yasuhide, Tsuji, Shingo, Tatsuno, Kenji, Takahashi, Hidekazu, Takahashi, Naoki, Takahashi, Masanobu, Shimodaira, Hideki, Aburatani, Hiroyuki, Ishioka, Chikashi
Format: Article
Language:English
Subjects:
Adenocarcinoma - genetics
Adenocarcinoma - mortality
Adult
Aged
Antineoplastic Agents - therapeutic use
Anti‐EGFR treatment
biomarker
Biomarkers
Biomarkers, Tumor - analysis
Biomarkers, Tumor - genetics
Cancer
Cancer therapies
Chemotherapy
Cluster Analysis
Colorectal cancer
Colorectal carcinoma
Colorectal Neoplasms - drug therapy
Colorectal Neoplasms - genetics
Colorectal Neoplasms - pathology
Deoxyribonucleic acid
Disease control
Disease-Free Survival
DNA
DNA methylation
DNA Methylation - genetics
Epidermal growth factor
Epidermal growth factor receptors
ErbB Receptors - immunology
Female
Genes
Genomes
Humans
Kaplan-Meier Estimate
Male
Medical prognosis
Medical records
Metastases
Metastasis
Middle Aged
molecular targeted therapy
Mutation
Neoplasm Metastasis
Oligonucleotide Array Sequence Analysis
Original
Patients
Quality control
Retrospective Studies
Studies
Survival
Tumors
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Summary:Anti‐epidermal growth factor receptor (EGFR) treatment is an effective option for metastatic colorectal cancer (CRC) treatment. However, there are few reliable biomarkers to predict the clinical response to anti‐EGFR treatment. We investigated the genome‐wide DNA methylation status in metastatic colorectal cancer to identify associations between the methylation status and clinical response to anti‐EGFR antibody. We retrospectively reviewed the medical records of 97 patients (45 patients for the first cohort and 52 patients for the second cohort) who received anti‐EGFR treatment for KRAS wild‐type metastatic CRC. Then we analyzed the associations between genome‐wide DNA methylation status and clinical response to anti‐EGFR treatment, and evaluated the predictive power and value of the methylation status statistically. As a result, each cohort was classified into highly methylated CRC and low methylated CRC subgroups by unsupervised clustering analyses. In the first cohort, clinical outcomes were significantly better in the low methylated CRC subgroup than in the highly methylated CRC subgroup (response rate, 35.7% vs 6.3%, P = 0.03; disease control rate, 75% vs 31.3%, P = 0.005; hazard ratio for progression‐free survival, 0.27; 95% confidence interval, 0.13–0.57, P 
ISSN:1347-9032
1349-7006
DOI:10.1111/cas.12827