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An online tool for the validation of
survival-predicting biomarkers in non small-cell
lung cancer using microarray data of 1,329 1,715
patients
Balázs Gyorffy and András LánczkyResearch
Laboratory for Pediatrics and Nephrology,
Hungarian Academy of Sciences and Semmelweis
University 1st Dept. of Pediatrics, Budapest,
Hungary
Background and Objective
Results

• optimized treatment for non-small cell lung
  cancer had lead to improved prognosis, but the
  overall survival is still very short
• by identifying biomarkers related to survival we
  can further understand the molecular basis of the
  disease
• OBJECTIVE we present the development of an
  online available tool suitable for the real-time
  meta-analysis of published lung cancer microarray
  datasets to identify biomarkers related to
  survival

• DATABASE construction
• n1,715
• Median OS40.0 months, age 64/-10 yrs
• Histology (adeno/squamous/large) 50 / 45 / 5
• Stage 1/2/3/4 63 / 27 / 10 / 1
• META-ANALYSIS of biomarker candidates
• Biomarker candidates identified in Pubmed n22
• For each gene the exact conditions in which it
  was identified have been retrieved, and these
  have been used as filtering when selecting the
  patients for the survival analysis.
• Of the 22, the best performing genes are
• n(1) number of patients in original study,
  n(2) number of patients in the KM-plotter, HR
  hazard ratio, ADE adenocarcinoma, NSCLC all
  non-small-cell lung cancer patients

Materials Methods
Symbol Reference n(1) Cohort n(2) HR p value
VEGF Zhan et al 2009 5386 NSCLC 1404 1.9 3.3e-10
Cyclin E Huang et al 2012 2606 NSCLC 1404 1.59 2.3e-09
Cyclin E Huang et al 2012 2606 ADE 486 2.44 4.8e-08
CDK1 Zhang et al 2012a 2731 NSCLC 1404 2.56 lt1e-16
CADM1 Botling et al 2012 617 ADE 486 0.38 7e-12
CDKN2A Jin et al 2001 106 NSCLC 1404 1.65 1.8e-09
CD24 Lee et al 2010 267 ADE 486 2.45 3.6e-10
ERCC1 Simon et al 2005 51 NSCLC 1404 1.65 1.4e-10

• DATABASE construction
• Repositories GEO, TCGA, ArrayExpress, caBIG
• Platforms Affymetrix HGU133A, plus2 A 2.0
  arrays
• at least 30 patients with survival information
• MAS5 normalization quality control
• SURVIVAL analysis
• Kaplan-Meier plot
• survival Bioconductor package
• Cox univariate multivariate analysis
• ONLINE platform
• Apache web server on Debian Linux
• script developed in PHP
• Open access at www.kmplot.com/lung

Cyclin E1
CDK1
CADM1
Summary

• we performed a meta-analysis of
  survival-associated genes
• an integrated database and an online tool for
  future in silico validation of new candidates has
  been established

Web addresses
Online access http//www.kmplot.com/lung Group
homepage http//gyer1-6.sote.hu/gyorffy Contact
gyorffy_at_kmplot.com
Grant support OTKA PD 83154, PREDICT 259303 (EU
Health.2010.2.4.1.-8), KTIA EU_BONUS_12-1-2013-000
3, Alexander von Humboldt-Foundation