Background: Previously, 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.
Methods: SLC19A3 gene expression was examined by RT-qPCR. Methylation status of SLC19A3 promoter was evaluated by methylation-specific qPCR. A robust and simple methylation-sensitive restriction enzyme digestion and real-time quantitative PCR assay was developed to quantify SLC19A3 DNA methylation in plasma. Results: Expression of SLC19A3 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 < 0.05). A total of 155 independent plasma samples from participants including 60 breast cancer, 45 gastric cancer patients and 60 healthy subjects were analyzed. Plasma methylated SLC19A3 DNA yielded a ROC curve area of 77%, sensitivity of 82% and specificity of 60% in discriminating breast cancer from control subjects. This marker yielded a ROC curve area of 87%, sensitivity of 90.0% and specificity of 62% in discriminating gastric cancer from control subjects. Elevated level in plasma has been detected not only in advanced stages but also early stages of tumors. Intriguingly, of all DCIS cases from breast cancer patients this plasma marker generated a ROC value of 92%, sensitivity of 100% and specificity of 78% in discriminating DCIS cases from controls. Conclusions: These results suggested that aberrant SLC19A3 promoter hypermethylation in plasma may be a novel biomarker for early breast cancer diagnosis.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-01-02.
Case A two-year-old boy was admitted because of colicky abdominal pain and repeated vomiting of about ten times for one day. Physical examination revealed normal blood pressure and pulse rate; abdomen was soft with mild tenderness on palpation. Blood tests including complete blood count, liver and renal functions were normal. An abdominal radiograph was taken. It showed mildly distended bowel loop with absence of bowel gas in the right upper and lower abdomen. There was a soft tissue mass seen in the right upper abdomen. Meniscus sign was also present. No obvious free gas was noted (Figure 1).
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