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

Abstract

Purpose: 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).Experimental Design: 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.Results: A methylation panel of 6 genes (CDO1, HOXA9, AJAP1, PTGDR, UNCX, and MARCH11) 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 CDO1, HOXA9, PTGDR, and AJAP1 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 HOXA9 methylation, showed poor outcomes.Conclusions: 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. Clin Cancer Res; 23(22); 7141-52. ©2017 AACR.

• Authors: Akira Ooki, Zahra Maleki, Jun-Chieh J Tsay, Chandra Goparaju, Mariana Brait, Nitesh Turaga, Hae-Seong Nam, William N Rom, Harvey I Pass, David Sidransky, Rafael Guerrero-Preston, Mohammad Obaidul Hoque
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 23 Issue 22 Pg. 7141-7152 (Nov 15 2017) ISSN: 1557-3265 [Electronic] United States
• PMID: 28855354 (Publication Type: Journal Article)
• Copyright: ©2017 American Association for Cancer Research.

Chemical References

• Biomarkers, Tumor
• Circulating Tumor DNA

Topics

• Adult
• Aged
• Aged, 80 and over
• Biomarkers, Tumor
• Carcinoma, Non-Small-Cell Lung (blood, diagnosis, genetics, mortality)
• Circulating Tumor DNA
• Combined Modality Therapy
• CpG Islands
• DNA Methylation
• Early Detection of Cancer
• Epigenesis, Genetic
• Female
• Gene Expression Profiling
• Humans
• Kaplan-Meier Estimate
• Lung Neoplasms (blood, diagnosis, genetics, mortality)
• Male
• Middle Aged
• Neoplasm Staging
• Pleural Effusion, Malignant (genetics, metabolism)
• Prognosis
• Promoter Regions, Genetic