A panel of novel detection and prognostic methylated DNA markers in primary non–small cell lung cancer and serum DNA

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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)7141-7152
Number of pages12
JournalClinical Cancer Research
Volume23
Issue number22
DOIs
StatePublished - Nov 15 2017

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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