TY - JOUR
T1 - Detection of Promoter DNA Methylation in Urine and Plasma Aids the Detection of Non–Small Cell Lung Cancer
AU - Liu, Bin
AU - Filho, Julio Ricarte
AU - Mallisetty, Apurva
AU - Villani, Cassandra
AU - Kottorou, Anastasia
AU - Rodgers, Kristen
AU - Chen, Chen
AU - Ito, Tomoaki
AU - Holmes, Kyla
AU - Gastala, Nicole
AU - Valyi-Nagy, Klara
AU - David, Odile
AU - Gaba, Ron C.
AU - Ascoli, Christian
AU - Pasquinelli, Mary
AU - Feldman, Lawrence E.
AU - Massad, Malek G.
AU - Wang, Tza Huei
AU - Jusue-Torres, Ignacio
AU - Benedetti, Enrico
AU - Winn, Robert A.
AU - Brock, Malcolm V.
AU - Herman, James G.
AU - Hulbert, Alicia
N1 - Funding Information:
This work was supported by grants from The University of Illinois at Chicago Cancer Center, EDRN U01CA214165-03 and DOD W81XWH-12-1-0323, and in part, under a grant with the Pennsylvania Department of Health.
Publisher Copyright:
©2020 American Association for Cancer Research.
PY - 2020/8/15
Y1 - 2020/8/15
N2 - 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 ¼ 74) had pathologic confirmation of NSCLC. Controls (n ¼ 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.
AB - 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 ¼ 74) had pathologic confirmation of NSCLC. Controls (n ¼ 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.
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U2 - 10.1158/1078-0432.CCR-19-2896
DO - 10.1158/1078-0432.CCR-19-2896
M3 - Article
C2 - 32430478
AN - SCOPUS:85089786762
SN - 1078-0432
VL - 26
SP - 4339
EP - 4348
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 16
ER -