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NIH Research Festival

September 16 – 18, 2015

An Integrated Prognostic Classifier for Stage I Lung Adenocarcinoma based on mRNA, microRNA and DNA Methylation Biomarkers

Thursday, September 17, 2015 – Poster Session II
12:00 – 1:30 p.m.

FAES Terrace

NCI

CANCER-30

Authors

  • AI Robles
  • E Arai
  • EA Mathe
  • H Okayama
  • AJ Schetter
  • D Petersen
  • ED Bowman
  • R Noro
  • JA Welsh
  • DC Edelman
  • HS Stevenson
  • Y Wang
  • A Haugen
  • PS Meltzer
  • J Yokota
  • Y Kanai
  • CC Harris

Abstract

Up to 30% of Stage I lung cancer patients will succumb to metastatic disease within 5 years of curative surgery. Therefore, there is a need for biomarkers that provide information about likelihood of recurrence. We analyzed the lung cancer epigenome and discovered methylation biomarkers that improve existing protein-coding gene and microRNA expression prognostic classifiers. We retrospectively analyzed tissue samples from patients with early stage lung cancer by genome-wide screening of DNA methylation followed by pyrosequencing. The prognostic significance of HOXA9 promoter methylation alone and in combination with four protein-coding gene (XPO1, BRCA1, HIF1α, DLC1), and miR-21 expression was assessed by Cox regression and Kaplan-Meier in two independently collected cohorts of Stage I lung adenocarcinoma. Promoters of genes marked by Polycomb in Embryonic Stem Cells were methylated de novo in tumors and identified patients with poor prognosis. High HOXA9 promoter methylation was associated with worse cancer-specific survival (Hazard Ratio [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 Stage IA and IB. Protein-coding gene, miR-21 and HOXA9 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 naïve, Stage I patients (HR, 10.2; P = 3x10-5). A prognostic classifier comprising three types of genomic and epigenomic data, may help guide the postoperative management of Stage I lung cancer patients at high risk of recurrence.

Scientific Focus Area: Cancer Biology

This page was last updated on Friday, March 26, 2021

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Current Research Festival

  • 2025
  • 2024
    • General Schedule of Events
    • 2024 NIH Distinguished Scholars Program
    • Poster Sessions
    • Concurrent Workshops
    • NIH Resource Information Fair
    • National Academy of Science Mini-Symposium
    • Special Wednesday Events
    • Vendor Exhibit Information
    • Green Labs Fair
    • Research Festival Committee
  • 2023
    • General Schedule of Events
    • NIH Early–Career Investigator Lectures
    • Poster Sessions
    • Concurrent Workshops
    • NIH Resource Information Fair
    • Vendor Exhibit Information
    • Research Festival Committee
  • 2021
  • 2019
    • General Schedule of Events
    • Plenary Sessions
    • Poster Session
    • Data Blitz
    • FARE Award Ceremony
    • Special Exhibits on Resources for Intramural Research
    • Technical Sales Association (TSA) Research Festival Exhibit Tent Show
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  • 2018
    • General Schedule of Events
    • Plenary Sessions
    • Concurrent Symposia Sessions
    • Poster Sessions
    • FARE Award Ceremony
    • Special Exhibits on Resources for Intramural Research
    • Technical Sales Association (TSA) Research Festival Exhibit Tent Show
    • Research Festival Committees
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    • General Schedule of Events
    • Plenary Sessions
    • Concurrent Symposia Sessions
    • Poster Sessions
    • FARE Award Ceremony
    • Future Research Leaders
    • Special Exhibits on Resources for Intramural Research
    • Technical Sales Association (TSA) Research Festival Exhibit Tent Show
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  • 2016
    • General Schedule of Events
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    • Browse by Presenter Name
    • Browse by Presenter IC
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    • Tours of the National Library of Medicine and Clinical Center
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  • 2015
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    • Plenary Sessions
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    • Browse by Presenter Name
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