Detection of Promoter DNA Methylation in Urine and Plasma Aids the Detection of Non-Small Cell Lung Cancer.
Abstact
Low-dose CT screening can reduce lung cancer-related mortality. However, CT screening has an FDR of nearly 96%. We sought to assess whether urine samples can be a source for DNA methylation-based detection of non-small cell lung cancer (NSCLC).
This nested case-control study of subjects with suspicious nodules on CT imaging obtained plasma and urine samples preoperatively. Cases (<i>n</i> = 74) had pathologic confirmation of NSCLC. Controls (<i>n</i> = 27) had a noncancer diagnosis. We detected promoter methylation in plasma and urine samples using methylation on beads and quantitative methylation-specific real-time PCR for cancer-specific genes (<i>CDO1, TAC1, HOXA7, HOXA9, SOX17</i>, and <i>ZFP42</i>).
DNA methylation at cancer-specific loci was detected in both plasma and urine, and was more frequent in patients with cancer compared with controls for all six genes in plasma and in <i>CDO1, TAC1, HOXA9</i>, and <i>SOX17</i> in urine. Univariate and multivariate logistic regression analysis showed that methylation detection in each one of six genes in plasma and <i>CDO1, TAC1, HOXA9</i>, and <i>SOX17</i> in urine were significantly associated with the diagnosis of NSCLC, independent of age, race, and smoking pack-years. When methylation was detected for three or more genes in both plasma and urine, the sensitivity and specificity for lung cancer diagnosis were 73% and 92%, respectively.
DNA methylation-based biomarkers in plasma and urine could be useful as an adjunct to CT screening to guide decision-making regarding further invasive procedures in patients with pulmonary nodules.
Authors
- Ascoli C
- Benedetti E
- Brock MV
- Chen C
- David O
- Feldman LE
- Gaba RC
- Gastala N
- Herman JG
- Holmes K
- Hulbert A
- Ito T
- Jusue-Torres I
- Kottorou A
- Liu B
- Mallisetty A
- Massad MG
- Pasquinelli M
- Ricarte Filho J
- Rodgers K
- Valyi-Nagy K
- Villani C
- Wang TH
- Winn RA