Abstract
BackgroundAberrant DNA methylation patterns might be used as a biomarker for diagnosis and management of cancer patients.Methods and FindingsTo achieve a gene panel for developing a breast cancer blood-based test we quantitatively assessed the DNA methylation proportion of 248 CpG sites per sample (total of 31,248 sites in all analyzed samples) on 10 candidate genes (APC, BIN1, BMP6, BRCA1, CST6, ESR-b, GSTP1, P16, P21 and TIMP3). The number of 126 samples consisting of two different cohorts was used (first cohort: plasma samples from breast cancer patients and normal controls; second cohort: triple matched samples including cancerous tissue, matched normal tissue and serum samples). In the first cohort, circulating cell free methylated DNA of the 8 tumor suppressor genes (TSGs) was significantly higher in patients with breast cancer compared to normal controls (P<0.01). In the second cohort containing triple matched samples, seven genes showed concordant hypermethylated profile in tumor tissue and serum samples compared to normal tissue (P<0.05). Using eight genes as a panel to develop a blood-based test for breast cancer, a sensitivity and specificity of more than 90% could be achieved in distinguishing between tumor and normal samples.ConclusionsOur study suggests that the selected TSG panel combined with the high-throughput technology might be a useful tool to develop epigenetic based predictive and prognostic biomarker for breast cancer relying on pathologic methylation changes in tumor tissue, as well as in circulation.
Highlights
Breast cancer is one of the most common types of cancer among women
Our study suggests that the selected tumor suppressor genes (TSGs) panel combined with the high-throughput technology might be a useful tool to develop epigenetic based predictive and prognostic biomarker for breast cancer relying on pathologic methylation changes in tumor tissue, as well as in circulation
We analyzed the methylation proportion of 10 breast cancer candidate genes in 126 different samples consisting of two different cohorts (36 plasma samples from patients with breast cancer and 30 plasma samples from normal controls, as well as 60 triple matched samples containing cancerous tissue, normal tissue and serum from 20 breast cancer patients)
Summary
Localized breast cancer at an early stage has better prognosis and requires less severe treatment with a survival rate of 98% [1]. Diagnosis after tumor metastasis lowers the survival rate to 27% [2]. This highlights the importance of early breast cancer detection which is dependent on sensitive and specific screening methods. The traditional triple test for breast cancer diagnosis includes physical examination, mammography and aspiration cytology. All these methods are not sensitive enough in identifying breast cancer in early stages [1,3]. Aberrant DNA methylation patterns might be used as a biomarker for diagnosis and management of cancer patients
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
