INTRODUCTION: Up to 30% @entity5 @entity1 suffer recurrence within 5 years of curative surgery. We sought to improve existing protein-coding gene and microRNA expression prognostic classifiers by incorporating epigenetic biomarkers. METHODS: Genome-wide screening of DNA methylation and pyrosequencing analysis of @entity29475 promoter methylation were performed in two independently collected cohorts of @entity2 . The prognostic value of @entity29475 promoter methylation alone and in combination with mRNA and miRNA biomarkers was assessed by Cox regression and Kaplan-Meier survival analysis in both cohorts. RESULTS: Promoters of genes marked by polycomb in embryonic stem cells were methylated de novo in @entity5 and identified @entity1 with poor prognosis. The @entity29475 locus was methylated de novo in stage I @entity5 (p < 0.0005). High @entity29475 promoter methylation was associated with worse @entity5 -specific survival (hazard ratio [HR], 2.6; p = 0.02) and recurrence-free survival (HR, 3.0; p = 0.01), and identified high-risk @entity1 in stratified analysis of stages IA and IB. Four protein-coding gene ( @entity15200 , @entity5345 , @entity7738 , and @entity21158 ), @entity10017 expression, and @entity29475 promoter methylation were each independently associated with outcome (HR, 2.8; p = 0.002; HR, 2.3; p = 0.01; and HR, 2.4; p = 0.005, respectively), and when combined, identified high-risk, therapy naive, stage I @entity1 (HR, 10.2; p = 3   *   10). All associations were confirmed in two independently collected cohorts. CONCLUSION: A prognostic classifier comprising three types of genomic and epigenomic data may help guide the postoperative management of @entity5 @entity1 at high risk of recurrence.

An Integrated Prognostic Classifier for XXXX Based on mRNA, microRNA, and DNA Methylation Biomarkers.

@entity1 :: ('9606', 'Species') :: ['patients'] @entity7738 :: ('3091', 'Gene') :: ['HIF1a'] @entity5 :: ('MESH:D009369', 'Disease') :: ['stage I lung cancer', 'cancer', 'tumors'] @entity5345 :: ('672', 'Gene') :: ['BRCA1'] @entity21158 :: ('10395', 'Gene') :: ['DLC1'] @entity29475 :: ('3205', 'Gene') :: ['HOXA9'] @entity2 :: ('MESH:D008175', 'Disease') :: ['stage I lung adenocarcinoma'] @entity10017 :: ('406991', 'Gene') :: ['miR-21'] @entity15200 :: ('7514', 'Gene') :: ['XPO1']
@entity2 :: (MESH:D008175,Disease) :: ['Stage I Lung Adenocarcinoma']
