A Panel of Novel Detection and Prognostic Methylated DNA Markers in Primary Non-Small Cell Lung Cancer and Serum DNA

• Published in: Clinical cancer research Vol. 23; no. 22; pp. 7141 - 7152
• Main Authors: Ooki, Akira, Maleki, Zahra, Tsay, Jun-Chieh J, Goparaju, Chandra, Brait, Mariana, Turaga, Nitesh, Nam, Hae-Seong, Rom, William N, Pass, Harvey I, Sidransky, David, Guerrero-Preston, Rafael, Hoque, Mohammad Obaidul
• Format: Journal Article
• Language: English
• Published: United States American Association for Cancer Research Inc 15-11-2017
• Subjects: Adult; Aged; Aged, 80 and over; Ascites; Biomarkers; Biomarkers, Tumor; Body fluids; Cancer; Carcinoma, Non-Small-Cell Lung - blood; Carcinoma, Non-Small-Cell Lung - diagnosis; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - mortality; Circulating Tumor DNA; Combined Modality Therapy; CpG Islands; Deoxyribonucleic acid; Diagnostic systems; DNA; DNA Methylation; Early Detection of Cancer; Epigenesis, Genetic; Experimental design; Female; Gene Expression Profiling; Genes; Genomes; Humans; Kaplan-Meier Estimate; Lung cancer; Lung Neoplasms - blood; Lung Neoplasms - diagnosis; Lung Neoplasms - genetics; Lung Neoplasms - mortality; Male; Middle Aged; Neoplasm Staging; Non-small cell lung carcinoma; Pleural effusion; Pleural Effusion, Malignant - genetics; Pleural Effusion, Malignant - metabolism; Prognosis; Promoter Regions, Genetic
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.ccr-17-1222

To establish a novel panel of cancer-specific methylated genes for cancer detection and prognostic stratification of early-stage non-small cell lung cancer (NSCLC).
Identification of differentially methylated regions (DMR) was performed with bumphunter on "The Cancer Genome Atlas (TCGA)" dataset, and clinical utility was assessed using quantitative methylation-specific PCR assay in multiple sets of primary NSCLC and body fluids that included serum, pleural effusion, and ascites samples.
A methylation panel of 6 genes (
, and
) was selected from TCGA dataset. Promoter methylation of the gene panel was detected in 92.2% (83/90) of the training cohort with a specificity of 72.0% (18/25) and in 93.0% (40/43) of an independent cohort of stage IA primary NSCLC. In serum samples from the later 43 stage IA subjects and population-matched 42 control subjects, the gene panel yielded a sensitivity of 72.1% (31/41) and specificity of 71.4% (30/42). Similar diagnostic accuracy was observed in pleural effusion and ascites samples. A prognostic risk category based on the methylation status of
, and
refined the risk stratification for outcomes as an independent prognostic factor for an early-stage disease. Moreover, the paralog group for HOXA9, predominantly overexpressed in subjects with
methylation, showed poor outcomes.
Promoter methylation of a panel of 6 genes has potential for use as a biomarker for early cancer detection and to predict prognosis at the time of diagnosis.
.