Experiment ID | EXP00299 |
Reference | Title: An Integrated Prognostic Classifier for Stage I Lung Adenocarcinoma Based onmRNA, microRNA, and DNA Methylation Biomarkers. Author: Robles AI, Arai E, Mathé EA, Okayama H, Schetter AJ, Brown D, Petersen D,Bowman ED, Noro R, Welsh JA, Edelman DC, Stevenson HS, Wang Y, Tsuchiya N, Kohno T, Skaug V, Mollerup S, Haugen A, Meltzer PS, Yokota J, Kanai Y, Harris CC. Journal: J Thorac Oncol. 2015 Jul;10(7):1037-48. doi: 10.1097/JTO.0000000000000560. Abstract: INTRODUCTION: Up to 30% stage I lung cancer patients suffer recurrence within 5years of curative surgery. We sought to improve existing protein-coding gene and microRNA expression prognostic classifiers by incorporating epigeneticbiomarkers.METHODS: Genome-wide screening of DNA methylation and pyrosequencing analysis of HOXA9 promoter methylation were performed in two independently collected cohorts of stage I lung adenocarcinoma. The prognostic value of HOXA9 promotermethylation 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 weremethylated de novo in tumors and identified patients with poor prognosis. TheHOXA9 locus was methylated de novo in stage I tumors (p < 0.0005). High HOXA9promoter methylation was associated with worse cancer-specific survival (hazardratio [HR], 2.6; p = 0.02) and recurrence-free survival (HR, 3.0; p = 0.01), and identified high-risk patients in stratified analysis of stages IA and IB. Fourprotein-coding gene (XPO1, BRCA1, HIF1α, and DLC1), miR-21 expression, and HOXA9 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 whencombined, identified high-risk, therapy naive, stage I patients (HR, 10.2; p =3 × 10). All associations were confirmed in two independently collected cohorts.CONCLUSION: A prognostic classifier comprising three types of genomic andepigenomic data may help guide the postoperative management of stage I lungcancer patients at high risk of recurrence. PMID: 26134223 |
Expressiion Profile | Description: Multi-platform Characterization of Stage I Lung Adenocarcinoma (miRNA profiling) Organism: Homo sapiens GEO ID: GSE63805 Platform: GPL18410 Number of samples: 62 |
Design and Sample | Cancer Type: lung cancer Cancer SubType: lung adenocarcinoma Cell Line: N/D Experimental Design: cancer vs normal Case Sample: lung adenocarcinoma Control Sample: normal lung Num of Case: 31 Num of Control: 30 Quantification Software: Limma Num of miRNAs: 654 |
Identification | Num of Up: 36 Num of Down: 42 |