期刊
BIOMEDICINES
卷 9, 期 10, 页码 -出版社
MDPI
DOI: 10.3390/biomedicines9101394
关键词
DNA methylation; diagnosis; epigenetic biomarker; diagnosis signature; triple-negative breast cancer
资金
- Sudoe European Regional Development Fund
- Breast Cancer Patients Association of Navarre (SARAY)
- Spanish Ministry of Science, Innovation and Universities [PTA2015-11895-I]
- University of Navarre (UPNA)
A novel DNA methylation signature with potential predictive value for TNBC diagnosis has been discovered. This signature was validated using various samples, confirming its effectiveness in TNBC and BC samples.
Triple-negative breast cancer (TNBC) is the most aggressive breast cancer (BC) subtype and lacks targeted treatment. It is diagnosed by the absence of immunohistochemical expression of several biomarkers, but this method still displays some interlaboratory variability. DNA methylome aberrations are common in BC, thereby methylation profiling could provide the identification of accurate TNBC diagnosis biomarkers. Here, we generated a signature of differentially methylated probes with class prediction ability between 5 non-neoplastic breast and 7 TNBC tissues (error rate = 0.083). The robustness of this signature was corroborated in larger cohorts of additional 58 non-neoplastic breast, 93 TNBC, and 150 BC samples from the Gene Expression Omnibus repository, where it yielded an error rate of 0.006. Furthermore, we validated by pyrosequencing the hypomethylation of three out of 34 selected probes (FLJ43663, PBX Homeobox 1 (PBX1), and RAS P21 protein activator 3 (RASA3) in 51 TNBC, even at early stages of the disease. Finally, we found significantly lower methylation levels of FLJ43663 in cell free-DNA from the plasma of six TNBC patients than in 15 healthy donors. In conclusion, we report a novel DNA methylation signature with potential predictive value for TNBC diagnosis.
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