Early Detection Research Network

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

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

Brait M, Goparaju C, Guerrero-Preston R, Hoque MO, Maleki Z, Nam HS, Ooki A, Pass HI, Rom WN, Sidransky D, Tsay JJ, Turaga N


Clin. Cancer Res., 2017, 23 (22)

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