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Clin Cancer Res. 2017 Apr 15;23(8):1998-2005. doi: 10.1158/1078-0432.CCR-16-1371. Epub 2016 Oct 11.

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

Author information

1
Sidney Kimmel Cancer Center, Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
2
Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
3
Department of Neurosurgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
4
Department of Mechanical Engineering, The Johns Hopkins University, Baltimore, Maryland.
5
Department of Thoracic Surgery, Second Xiangya Hospital of Central South University, Changsha, Hunan, PR China.
6
Department of Biostatistics, The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
7
Department of Medicine, Medical University of South Carolina, Charleston, South Carolina.
8
Lung Cancer Program, Lovelace Respiratory Research Institute, Albuquerque, New Mexico.
9
Department of Biomedical Engineering and Institute for NanoBioTechnology, The Johns Hopkins University, School of Medicine, Baltimore, Maryland.
10
Sidney Kimmel Cancer Center, Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland. hermanj3@upmc.edu.
11
Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.

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.

PMID:
27729459
PMCID:
PMC6366618
DOI:
10.1158/1078-0432.CCR-16-1371
[Indexed for MEDLINE]
Free PMC Article

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