期刊
TUMOR BIOLOGY
卷 37, 期 10, 页码 13111-13119出版社
SAGE PUBLICATIONS LTD
DOI: 10.1007/s13277-016-5190-z
关键词
Breast cancer; Plasma; Methylation; Cell-free DNA; Next-generation sequencing; Microfludic PCR
类别
资金
- Natural Science Foundation of China [81272296, 81372228]
- Scientific Project of China Hunan Provincial Science and Technology Department [2012SK2013]
- Major Special Projects of the Science and Technology Bureau of Changsha, China [K1204017-31, K1306011-31]
- Hunan Province Postgraduate Student Scientific Innovation Project, China [CX2013B087]
Circulating cell-free DNA (cfDNA) has been considered as a potential biomarker for non-invasive cancer detection. To evaluate the methylation levels of six candidate genes (EGFR, GREM1, PDGFRB, PPM1E, SOX17, and WRN) in plasma cfDNA as biomarkers for breast cancer early detection, quantitative analysis of the promoter methylation of these genes from 86 breast cancer patients and 67 healthy controls was performed by using microfluidic-PCR-based target enrichment and next-generation bisulfite sequencing technology. The predictive performance of different logistic models based on methylation status of candidate genes was investigated by means of the area under the ROC curve (AUC) and odds ratio (OR) analysis. Results revealed that EGFR, PPM1E, and 8 gene-specific CpG sites showed significantly hypermethylation in cancer patients' plasma and significantly associated with breast cancer (OR ranging from 2.51 to 9.88). The AUC values for these biomarkers were ranging from 0.66 to 0.75. Combinations of multiple hypermethylated genes or CpG sites substantially improved the predictive performance for breast cancer detection. Our study demonstrated the feasibility of quantitative measurement of candidate gene methylation in cfDNA by using microfluidic-PCR-based target enrichment and bisulfite next-generation sequencing, which is worthy of further validation and potentially benefits a broad range of applications in clinical oncology practice. Quantitative analysis of methylation pattern of plasma cfDNA by next-generation sequencing might be a valuable non-invasive tool for early detection of breast cancer.
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