1. Noninvasive discrimination of benign and malignant breast lesions using genome-wide nucleosome profiles of plasma cell-free DNA
- Author
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Ouyang Guojun, Xue-Xi Yang, Guo-Lin Ye, Bo-Wei Han, Li-Min Huang, Zhi-Wei Guo, Kun Li, Qing Liu, Xu Yang, Geng-Xi Cai, and Ying-Song Wu
- Subjects
0301 basic medicine ,Pathology ,medicine.medical_specialty ,Clinical Biochemistry ,Breast Neoplasms ,Breast malignancy ,Plasma cell ,Malignancy ,Biochemistry ,Genome ,Diagnosis, Differential ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,Nucleosome ,Breast ,skin and connective tissue diseases ,Receiver operating characteristic ,business.industry ,Biochemistry (medical) ,Area under the curve ,General Medicine ,medicine.disease ,Nucleosomes ,030104 developmental biology ,medicine.anatomical_structure ,ROC Curve ,Cell-free fetal DNA ,030220 oncology & carcinogenesis ,Female ,business ,Cell-Free Nucleic Acids - Abstract
Background Breast malignancy is the most frequently diagnosed malignancy in women worldwide, and the diagnosis relies on invasive examinations. However, most clinical breast changes in women are benign, and invasive diagnostic approaches cause unnecessary suffering for the patients. Thus, a novel noninvasive approach for discriminating malignant breast lesions from benign lesions is needed. Methods We performed cell-free DNA (cfDNA) sequencing on plasma samples from 173 malignant breast lesion patients, 158 benign breast lesion patients, and 102 healthy women. We then analyzed the cfDNA-based nucleosome profiles, which reflect the various tissues of origin and transcription factor activities. Moreover, by using machine learning classifiers along with the cfDNA sequencing data, we built classifiers for discriminating benign from malignant breast lesions. Receiver operating characteristic curve analyses were used to evaluate the performance of the classifiers. Results cfDNA-based nucleosome profiles reflected the various tissues of origin and transcription factor activities in benign and malignant breast lesions. The cfDNA-based transcription factor activities and breast malignancy-specific transcription factor-binding site accessibility profiles could accurately distinguish benign and malignant breast lesions, with area under the curve values of 0.777 and 0.824, respectively. Conclusions Our proof-of-principle study established a methodology for noninvasively discriminating benign from malignant breast lesions.
- Published
- 2021