American Association for Cancer Research
10780432ccr192896-sup-228010_3_supp_6286082_qx1hp2.docx (51.09 kB)

Supplementary Table S9 from Detection of Promoter DNA Methylation in Urine and Plasma Aids the Detection of Non–Small Cell Lung Cancer

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journal contribution
posted on 2023-03-31, 22:07 authored by 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 Benedetti, Robert A. Winn, Malcolm V. Brock, James G. Herman, Alicia Hulbert

Gene Methylation Detection, Sensitivity, Specificity Using Detectable vs. Non-detectable cutoff in blacks






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 (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). 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. 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.