Genome-wide cell-free DNA methylation analyses improve accuracy of non-invasive diagnostic imaging for early-stage breast cancer
Open Access
- 19 February 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Molecular Cancer
- Vol. 20 (1), 1-7
- https://doi.org/10.1186/s12943-021-01330-w
Abstract
Early detection is crucial to improve breast cancer (BC) patients’ outcomes and survival. Mammogram and ultrasound adopting the Breast Imaging Reporting and Data System (BI-RADS) categorization are widely used for BC early detection, while suffering high false-positive rate leading to unnecessary biopsy, especially in BI-RADS category-4 patients. Plasma cell-free DNA (cfDNA) carrying on DNA methylation information has emerged as a non-invasive approach for cancer detection. Here we present a prospective multi-center study with whole-genome bisulfite sequencing data to address the clinical utility of cfDNA methylation markers from 203 female patients with breast lesions suspected for malignancy. The cfDNA is enriched with hypo-methylated genomic regions. A practical computational framework was devised to excavate optimal cfDNA-rich DNA methylation markers, which significantly improved the early diagnosis of BI-RADS category-4 patients (AUC from 0.78–0.79 to 0.93–0.94). As a proof-of-concept study, we performed the first blood-based whole-genome DNA methylation study for detecting early-stage breast cancer from benign tumors at single-base resolution, which suggests that combining the liquid biopsy with the traditional diagnostic imaging can improve the current clinical practice, by reducing the false-positive rate and avoiding unnecessary harms.Keywords
Funding Information
- National Natural Science Foundation of China (61871294, 81802669, 81501852, 81872149, 11701385, 81472046 and 81772299)
- Natural Science Foundation of Zhejiang Province (LR19C060001)
- Fundamental Research Funds for Wenzhou Institute of University of Chinese Academy of Sciences (WIBEZD2017009-05)
- Tsinghua University-Peking Union Medical College Hospital Initiative Scientific Research Program
- CAMS Initiative Fund for Medical Sciences (2016-I2M-3-003, 2016-I2M-2-006 and 2017-I2M-2-001, 2016-I2M-1-001)
- National Key Research and Development Program of China (2018YFC0910506)
- CAMS Innovation Fund for Medical Sciences (2020-I2M-C&T-B-068)
- Beijing Natural Science Foundation (JQ20032)
- non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences
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