lunes, 10 de noviembre de 2014

The Expression of Four Genes as a Prognostic Classifier for Stage I Lung Adenocarcinoma in 12 Independent Cohorts

The Expression of Four Genes as a Prognostic Classifier for Stage I Lung Adenocarcinoma in 12 Independent Cohorts



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The Expression of Four Genes as a Prognostic Classifier for Stage I Lung Adenocarcinoma in 12 Independent Cohorts

  1. Curtis C. Harris1,*
+Author Affiliations
  1. 1Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland.
  2. 2Division of Genome Biology, National Cancer Center Research Institute, Tokyo, Japan.
  3. 3Genomics and Epigenomics of Cancer Prediction Program, Institute of Predictive and Personalized Medicine of Cancer, Barcelona, Spain.
  4. 4Department of Organ Regulatory Surgery, Fukushima Medical University School of Medicine, Fukushima, Japan.
  1. *Corresponding Author:
    Curtis C. Harris, Laboratory of Human Carcinogenesis, National Cancer Institute, NIH, 37 Convent Dr. MSC4258, Building 37, Room 3068A, Bethesda, MD 20892-4258. Phone: 301-496-2048; Fax: 301-496-0497; E-mail: Curtis_Harris@nih.gov
  1. H. Okayama and A.J. Schetter contributed equally to this article.

Abstract

Background: We previously developed a prognostic classifier using the expression levels of BRCA1, HIF1A, DLC1, and XPO1 that identified stage I lung adenocarcinoma patients with a high risk of relapse. That study evaluated patients in five independent cohorts from various regions of the world. In an attempt to further validate the classifier, we have used a meta-analysis–based approach to study 12 cohorts consisting of 1,069 tumor–node–metastasis stage I lung adenocarcinoma patients from every suitable, publically available dataset.
Methods: Cohorts were obtained through a systematic search of public gene expression datasets. These data were used to calculate the risk score using the previously published 4-gene risk model. A fixed effect meta-analysis model was used to generate a pooled estimate for all cohorts.
Results: The classifier was associated with prognosis in 10 of the 12 cohorts (P < 0.05). This association was highly consistent regardless of the ethnic diversity or microarray platform. The pooled estimate demonstrated that patients classified as high risk had worse overall survival for all stage I [HR, 2.66; 95% confidence interval (CI), 1.93–3.67; P < 0.0001] patients and in stratified analyses of stage IA (HR, 2.69; 95% CI, 1.66–4.35; P < 0.0001) and stage IB (HR, 2.69; 95% CI, 1.74–4.16; P < 0.0001) patients.
Conclusions: The 4-gene classifier provides independent prognostic stratification of stage IA and stage IB patients beyond conventional clinical factors.
Impact: Our results suggest that the 4-gene classifier may assist clinicians in decisions about the postoperative management of early-stage lung adenocarcinoma patients. Cancer Epidemiol Biomarkers Prev; 1–11. ©2014 AACR.

Footnotes

  • Note: Supplementary data for this article are available at Cancer Epidemiology, Biomarkers & Prevention Online (http://cebp.aacrjournals.org/).
  • Received February 18, 2014.
  • Revision received September 15, 2014.
  • Accepted September 16, 2014.

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