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

Bin Liu, Julio Ricarte Filho, Apurva Mallisetty, Cassandra Villani, Anastasia Kottorou, Kristen Rodgers, Chen Chen, Tomoaki Ito, Kyla Holmes, Nicole Gastala, Klara Valyi-Nagy, Odile David, Ron C. Gaba, Christian Ascoli, Mary Pasquinelli, Lawrence E. Feldman, Malek G. Massad, Tza Huei Wang, Ignacio Jusue-Torres, Enrico BenedettiRobert A. Winn, Malcolm V. Brock, James G. Herman, Alicia Hulbert

Research output: Contribution to journalArticlepeer-review

Abstract

PURPOSE: 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). EXPERIMENTAL DESIGN: This nested case-control study of subjects with suspicious nodules on CT imaging obtained plasma and urine samples preoperatively. Cases (n = 74) had pathologic confirmation of NSCLC. Controls (n = 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 (CDO1, TAC1, HOXA7, HOXA9, SOX17, and ZFP42). RESULTS: 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 CDO1, TAC1, HOXA9, and SOX17 in urine. Univariate and multivariate logistic regression analysis showed that methylation detection in each one of six genes in plasma and CDO1, TAC1, HOXA9, and SOX17 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. CONCLUSIONS: 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.

Original languageEnglish (US)
Pages (from-to)4339-4348
Number of pages10
JournalClinical cancer research : an official journal of the American Association for Cancer Research
Volume26
Issue number16
DOIs
StatePublished - Aug 15 2020

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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