Detection of Promoter DNA Methylation in Urine and Plasma Aids the Detection of Non-Small Cell Lung Cancer.

Abstract

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
PubMed ID
Appears In
Clin Cancer Res, 2020, 26 (16)