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Updated: Mar 22, 2026
Methyl-binding DNA capture Sequencing for Patient Tissues
Published on: October 31, 2016
Pattern of RECK CpG methylation as a potential marker for predicting breast cancer prognosis and drug-sensitivity
Gongping Shi1, Yoko Yoshida2, Kanako Yuki2
1Department of Molecular Oncology, Kyoto University Graduate School of Medicine, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
Abstract:
The membrane-anchored glycoprotein RECK negatively regulates multiple metalloproteinases and is frequently downregulated in tumors. Forced RECK expression in cancer cells results in suppression of tumor angiogenesis, invasion, and metastasis in xenograft models. A previous methylome study on breast cancer tissues detected inverse correlation between RECK CpG methylation (in an intron-1 region) and relapse-free survival. In this study, we focused on another region of the RECK CpG island (a promoter/exon-1 region) and found an inverse correlation between its methylation and RECK-inducibility by an HDAC inhibitor, MS275, among a panel of breast cancer cell lines (n=15). In clinical samples (n=62), RECK intron-1 methylation was prevalent among luminal breast cancers as reported previously (26 of 38 cases; 68%) and particularly enriched in tumors of the ER+PR- subclass (10 of 10 cases) and of higher histological grades (Grade 2 and 3; 28 of 43 cases; P=0.006). In about a half of these cases, promoter/exon-1 methylation was absent, and hence, RECK may be inducible by certain drugs such as MS275. Our results indicate the value of combined use of two RECK methylation markers for predicting prognosis and drug-sensitivity of breast cancers.
Insights
RECK methylation in breast cancer predicts prognosis and drug response. Targeting RECK may offer new therapeutic strategies for specific breast cancer subtypes.
Area of Science:
- Oncology
- Epigenetics
- Cancer Biology
Background:
- The RECK glycoprotein inhibits tumor growth, angiogenesis, invasion, and metastasis.
- RECK downregulation in tumors correlates with poor prognosis.
- Previous studies linked RECK intron-1 methylation to reduced relapse-free survival in breast cancer.
Purpose of the Study:
- To investigate the methylation status of a RECK promoter/exon-1 region in breast cancer.
- To determine the correlation between RECK promoter/exon-1 methylation and RECK inducibility by HDAC inhibitors.
- To evaluate the clinical significance of RECK methylation in breast cancer prognosis and drug sensitivity.
Main Methods:
- Analysis of RECK CpG island methylation in breast cancer cell lines (n=15) and clinical samples (n=62).
- Correlation analysis between RECK methylation status and RECK inducibility by MS275 (an HDAC inhibitor).
- Assessment of RECK intron-1 methylation prevalence in different breast cancer subtypes and grades.
Main Results:
- RECK promoter/exon-1 methylation inversely correlated with RECK inducibility by MS275 in breast cancer cell lines.
- RECK intron-1 methylation was prevalent in luminal breast cancers, particularly in ER+PR- and higher-grade tumors.
- Absence of promoter/exon-1 methylation in some cases suggests potential for drug-induced RECK expression.
Conclusions:
- RECK promoter/exon-1 methylation influences drug-induced RECK expression.
- Combined analysis of RECK intron-1 and promoter/exon-1 methylation may predict breast cancer prognosis.
- These methylation markers could guide therapeutic strategies targeting RECK in breast cancer.
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