Abstract
BackgroundPreviously, we have examined the methylation status of SLC19A3 (solute carrier family 19, member 3) promoter and found that SLC19A3 was epigenetically down-regulated in gastric cancer. Here, we aim to develop a new biomarker for cancer diagnosis using methylated SLC19A3 DNA in plasma.Methodology/Principal FindingsSLC19A3 gene expression was examined by RT-qPCR. Methylation status of SLC19A3 promoter was evaluated by methylation-specific qPCR. SLC19A3 expression was significantly down-regulated in 80% (12/15) of breast tumors (P<0.005). Breast tumors had significant increase in methylation percentage when compared to adjacent non-tumor tissues (P<0.005). A robust and simple methylation-sensitive restriction enzyme digestion and real-time quantitative PCR (MSRED-qPCR) was developed to quantify SLC19A3 DNA methylation in plasma. We validated this biomarker in an independent validation cohort of 165 case-control plasma including 60 breast cancer, 45 gastric cancer patients and 60 healthy subjects. Plasma SLC19A3 methylated DNA level was effective in differentiating both breast and gastric cancer from healthy subjects. We further validated this biomarker in another independent blinded cohort of 78 plasma including 38 breast cancer, 20 gastric cancer patients and 20 healthy subjects. The positive predictive values for breast and gastric cancer were 90% and 85%, respectively. The negative predictive value of this biomarker was 85%. Elevated level in plasma has been detected not only in advanced stages but also early stages of tumors. The positive predictive value for ductal carcinoma in situ (DCIS) cases was 100%.ConclusionsThese results suggested that aberrant SLC19A3 promoter hypermethylation in plasma may be a novel biomarker for breast and gastric cancer diagnosis.
Highlights
Epigenetic changes, such as DNA methylation, are one of the most common molecular alterations in human cancer [1], including gastric [2] and breast cancer [3]
These results suggested that aberrant SLC19A3 promoter hypermethylation in plasma may be a novel biomarker for breast and gastric cancer diagnosis
Recent study has demonstrated that hypermethylation of RASSF1A DNA in serum is detected in gastric cancer [8] and is associated with a worse outcome in breast cancer patients [9]
Summary
Epigenetic changes, such as DNA methylation, are one of the most common molecular alterations in human cancer [1], including gastric [2] and breast cancer [3]. SLC19A3 (solute carrier family 19, member 3 or THTR-2, thiamine transporter-2) which has been found to be down-regulated in gastric and breast cancer [10,11,12], could be a potential candidate for this diagnostic purpose. Like folate and many other water-soluble micronutrients, thiamine was transported across the plasma membrane via a specialized carriermediated mechanism. It has been recognized for a long time that thiamine deficiency frequently occurs in cancer patients [16]. We have examined the methylation status of SLC19A3 (solute carrier family 19, member 3) promoter and found that SLC19A3 was epigenetically down-regulated in gastric cancer. We aim to develop a new biomarker for cancer diagnosis using methylated SLC19A3 DNA in plasma
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
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.
