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Early Detection of Lung Cancer Using DNA Promoter Hypermethylation in Plasma and Sputum.

ABSTRACT: Purpose: CT screening can reduce death from lung cancer. We sought to improve the diagnostic accuracy of lung cancer screening using ultrasensitive methods and a lung cancer-specific gene panel to detect DNA methylation in sputum and plasma.Experimental Design: This is a case-control study of subjects with suspicious nodules on CT imaging. Plasma and sputum were obtained preoperatively. Cases (n = 150) had pathologic confirmation of node-negative (stages I and IIA) non-small cell lung cancer. Controls (n = 60) had non-cancer diagnoses. We detected promoter methylation using quantitative methylation-specific real-time PCR and methylation-on-beads for cancer-specific genes (SOX17, TAC1, HOXA7, CDO1, HOXA9, and ZFP42).Results: DNA methylation was detected in plasma and sputum more frequently in people with cancer compared with controls (P < 0.001) for five of six genes. The sensitivity and specificity for lung cancer diagnosis using the best individual genes was 63% to 86% and 75% to 92% in sputum, respectively, and 65% to 76% and 74% to 84% in plasma, respectively. A three-gene combination of the best individual genes has sensitivity and specificity of 98% and 71% using sputum and 93% and 62% using plasma. Area under the receiver operating curve for this panel was 0.89 [95% confidence interval (CI), 0.80-0.98] in sputum and 0.77 (95% CI, 0.68-0.86) in plasma. Independent blinded random forest prediction models combining gene methylation with clinical information correctly predicted lung cancer in 91% of subjects using sputum detection and 85% of subjects using plasma detection.Conclusions: High diagnostic accuracy for early-stage lung cancer can be obtained using methylated promoter detection in sputum or plasma. Clin Cancer Res; 23(8); 1998-2005. ©2016 AACR.

SUBMITTER: Hulbert A

PROVIDER: S-EPMC6366618 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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Early Detection of Lung Cancer Using DNA Promoter Hypermethylation in Plasma and Sputum.

Hulbert Alicia A Jusue-Torres Ignacio I Stark Alejandro A Chen Chen C Rodgers Kristen K Lee Beverly B Griffin Candace C Yang Andrew A Huang Peng P Wrangle John J Belinsky Steven A SA Wang Tza-Huei TH Yang Stephen C SC Baylin Stephen B SB Brock Malcolm V MV Herman James G JG

Clinical cancer research : an official journal of the American Association for Cancer Research 20161011 8

Purpose: CT screening can reduce death from lung cancer. We sought to improve the diagnostic accuracy of lung cancer screening using ultrasensitive methods and a lung cancer-specific gene panel to detect DNA methylation in sputum and plasma.Experimental Design: This is a case-control study of subjects with suspicious nodules on CT imaging. Plasma and sputum were obtained preoperatively. Cases (n = 150) had pathologic confirmation of node-negative (stages I and IIA) non-small ...[more]

PMID: 27729459

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Project description:Gastric cancer (GC) remains one of the most common digestive cancers worldwide; however, most patients present at an advanced stage at initial diagnosis. Zic1 is a novel candidate tumor suppressor gene that is epigenetically silenced in GC. In this study, we investigated Zic1 promoter methylation in plasma DNA as a novel molecular marker for the early diagnosis and monitoring of GC. Methylation-specific polymerase chain reaction (MSP) assay was performed to detect Zic1 promoter methylation in plasma DNA from 20 healthy subjects, 50 gastric intraepithelial neoplasia patients, and 104 GC patients. The Zic1 promoter methylation rate in the plasma samples from the healthy control group was 0%, but it reached 54.0% in the intraepithelial neoplasia group and 60.6% in the GC group. The latter two values were significantly higher than that found in the healthy control group (p < 0.05), with a 100% specificity for intraepithelial neoplasia and GC diagnosis. The positive predictive value of plasma Zic1 promoter methylation for the diagnosis of intraepithelial neoplasia and GC was 100%. Methylation status in the GC group was not significantly associated with tumor size, tumor differentiation, lymph node metastasis, TNM staging, or tumor invasion (p > 0.05). Assessment of the significance of detection of the carcino-embryonic antigen (CEA) level and Zic1 promoter methylation rate for GC diagnosis revealed that the sensitivity of Zic1 promoter methylation was significantly higher than that of the CEA level as a marker and that the combined measurement of these two indices (parallel testing) improved sensitivity. Taken together, our results suggest that the Zic1 promoter methylation rate in plasma-derived DNA is of great significance for the early screening of GC and monitoring of tumorigenesis. Zic1 promoter methylation may serve as a novel non-invasive plasma biomarker for the early detection of GC and for risk assessment in high-risk populations. The combined measurement of the Zic1 promoter methylation rate and CEA level (parallel testing) may enhance the current guidelines for the early diagnosis of GC.

Dataset Information

Early Detection of Lung Cancer Using DNA Promoter Hypermethylation in Plasma and Sputum.

Publications

Early Detection of Lung Cancer Using DNA Promoter Hypermethylation in Plasma and Sputum.

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