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PMID: 24367507 Published · epublish English Journal Article Research Support, Non-U.S. Gov't

Online survival analysis software to assess the prognostic value of biomarkers using transcriptomic data in non-small-cell lung cancer.

PloS one ·Vol. 8 ·No. 12 ·2013-00-00 ·Pages e82241

Győrffy B, Surowiak P, Budczies J, Lánczky A

Abstract

In the last decade, optimized treatment for non-small cell lung cancer had lead to improved prognosis, but the overall survival is still very short. To further understand the molecular basis of the disease we have to identify biomarkers related to survival. Here we present the development of an online tool suitable for the real-time meta-analysis of published lung cancer microarray datasets to identify biomarkers related to survival. We searched the caBIG, GEO and TCGA repositories to identify samples with published gene expression data and survival information. Univariate and multivariate Cox regression analysis, Kaplan-Meier survival plot with hazard ratio and logrank P value are calculated and plotted in R. The complete analysis tool can be accessed online at: www.kmplot.com/lung. All together 1,715 samples of ten independent datasets were integrated into the system. As a demonstration, we used the tool to validate 21 previously published survival associated biomarkers. Of these, survival was best predicted by CDK1 (p<1E-16), CD24 (p<1E-16) and CADM1 (p = 7E-12) in adenocarcinomas and by CCNE1 (p = 2.3E-09) and VEGF (p = 3.3E-10) in all NSCLC patients. Additional genes significantly correlated to survival include RAD51, CDKN2A, OPN, EZH2, ANXA3, ADAM28 and ERCC1. In summary, we established an integrated database and an online tool capable of uni- and multivariate analysis for in silico validation of new biomarker candidates in non-small cell lung cancer.

MeSH Terms
Biomarkers Carcinoma, Non-Small-Cell Lung/genetics Humans Kaplan-Meier Estimate Lung Neoplasms/genetics Multivariate Analysis Proportional Hazards Models Software Transcriptome/genetics
Chemicals
Biomarkers
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Győrffy Balázs
Research Laboratory of Pediatrics and Nephrology, Hungarian Academy of Sciences, Budapest, Hungary.
Surowiak Pawel
Department of Histology and Embryology, Wroclaw Medical University, Wrocław, Poland.
Budczies Jan
Institut für Pathologie, Charité - Universitätsmedizin Berlin, Berlin, Germany.
Lánczky András
Research Laboratory of Pediatrics and Nephrology, Hungarian Academy of Sciences, Budapest, Hungary.
References (48)
48 references, click to expand
  1. Classification of human lung carcinomas by mRNA expression profiling reveals distinct adenocarcinoma subclasses.
    Proc Natl Acad Sci U S A. 2001 Nov 20;98(24):13790-5 PMID: 11707567
  2. Significance of S100A4 as a prognostic marker of lung squamous cell carcinoma.
    Anticancer Res. 2009 Jul;29(7):2547-54 PMID: 19596927
  3. Expression of X-linked inhibitor of apoptosis as a novel prognostic marker in radically resected non-small cell lung cancer patients.
    Clin Cancer Res. 2001 Aug;7(8):2468-74 PMID: 11489828
  4. Cigarette smoking and pancreas cancer: a case control study of the search programme of the IARC.
    Int J Cancer. 1996 Jul 3;67(1):63-71 PMID: 8690527
  5. High-level expression of Rad51 is an independent prognostic marker of survival in non-small-cell lung cancer patients.
    Br J Cancer. 2005 Jul 11;93(1):137-43 PMID: 15956972
  6. Epidermal growth factor receptor tyrosine kinase defines critical prognostic genes of stage I lung adenocarcinoma.
    PLoS One. 2012;7(9):e43923 PMID: 23028479
  7. Gene expression signatures for predicting prognosis of squamous cell and adenocarcinomas of the lung.
    Cancer Res. 2006 Aug 1;66(15):7466-72 PMID: 16885343
  8. Funnel plots for detecting bias in meta-analysis: guidelines on choice of axis.
    J Clin Epidemiol. 2001 Oct;54(10):1046-55 PMID: 11576817
  9. Prediction of recurrence-free survival in postoperative non-small cell lung cancer patients by using an integrated model of clinical information and gene expression.
    Clin Cancer Res. 2008 Nov 15;14(22):7397-404 PMID: 19010856
  10. Comprehensive genomic characterization of squamous cell lung cancers.
    Nature. 2012 Sep 27;489(7417):519-25 PMID: 22960745
  11. Prognostic value of vascular endothelial growth factor expression in patients with lung cancer: a systematic review with meta-analysis.
    J Thorac Oncol. 2009 Sep;4(9):1094-103 PMID: 19687765
  12. Constructing molecular classifiers for the accurate prognosis of lung adenocarcinoma.
    Clin Cancer Res. 2006 Jun 1;12(11 Pt 1):3344-54 PMID: 16740756
  13. Lung cancer incidence in never smokers.
    J Clin Oncol. 2007 Feb 10;25(5):472-8 PMID: 17290054
  14. Lung cancer: New biological insights and recent therapeutic advances.
    CA Cancer J Clin. 2011 Mar-Apr;61(2):91-112 PMID: 21303969
  15. Prediction of lymph node metastasis by analysis of gene expression profiles in primary lung adenocarcinomas.
    Clin Cancer Res. 2005 Jun 1;11(11):4128-35 PMID: 15930348
  16. ADAM28 is a serological and histochemical marker for non-small-cell lung cancers.
    Int J Cancer. 2010 Oct 15;127(8):1844-56 PMID: 20112342
  17. Prognostic factors in resected stage I non-small-cell lung cancer: a multivariate analysis of six molecular markers.
    J Clin Oncol. 2004 Nov 15;22(22):4575-83 PMID: 15542809
  18. Gene expression-based survival prediction in lung adenocarcinoma: a multi-site, blinded validation study.
    Nat Med. 2008 Aug;14(8):822-7 PMID: 18641660
  19. Gene expression profiling reveals reproducible human lung adenocarcinoma subtypes in multiple independent patient cohorts.
    J Clin Oncol. 2006 Nov 1;24(31):5079-90 PMID: 17075127
  20. Oncogenic pathway signatures in human cancers as a guide to targeted therapies.
    Nature. 2006 Jan 19;439(7074):353-7 PMID: 16273092
  21. Biomarker discovery in non-small cell lung cancer: integrating gene expression profiling, meta-analysis, and tissue microarray validation.
    Clin Cancer Res. 2013 Jan 1;19(1):194-204 PMID: 23032747
  22. Cancer statistics, 2012.
    CA Cancer J Clin. 2012 Jan-Feb;62(1):10-29 PMID: 22237781
  23. Enhancer of zeste homolog 2 is a novel prognostic biomarker in nonsmall cell lung cancer.
    Cancer. 2012 Mar 15;118(6):1599-606 PMID: 21837672
  24. Quantitative proteome analysis reveals annexin A3 as a novel biomarker in lung adenocarcinoma.
    J Pathol. 2009 Jan;217(1):54-64 PMID: 18798225
  25. Meta-analysis methods.
    Adv Genet. 2008;60:311-34 PMID: 18358326
  26. The role of cyclin D1 expression and patient's survival in non-small-cell lung cancer: a systematic review with meta-analysis.
    Clin Lung Cancer. 2012 May;13(3):188-95 PMID: 22133292
  27. Osteopontin expression in lung cancer.
    Lung Cancer. 1996 Nov;15(3):311-23 PMID: 8959677
  28. Gene expression-based classification of non-small cell lung carcinomas and survival prediction.
    PLoS One. 2010 Apr 22;5(4):e10312 PMID: 20421987
  29. A gene expression signature predicts survival of patients with stage I non-small cell lung cancer.
    PLoS Med. 2006 Dec;3(12):e467 PMID: 17194181
  30. Prognostic value of survivin in patients with non-small cell lung carcinoma: a systematic review with meta-analysis.
    PLoS One. 2012;7(3):e34100 PMID: 22457815
  31. Gene-expression profiles predict survival of patients with lung adenocarcinoma.
    Nat Med. 2002 Aug;8(8):816-24 PMID: 12118244
  32. Carcinoembryonic antigen and prognosis after radical surgery for lung cancer: immunocytochemical localization and serum levels.
    Br J Cancer. 1981 Aug;44(2):145-53 PMID: 7023523
  33. CD24, a novel cancer biomarker, predicting disease-free survival of non-small cell lung carcinomas: a retrospective study of prognostic factor analysis from the viewpoint of forthcoming (seventh) new TNM classification.
    J Thorac Oncol. 2010 May;5(5):649-57 PMID: 20354454
  34. Prognosis of women with metastatic breast cancer by HER2 status and trastuzumab treatment: an institutional-based review.
    J Clin Oncol. 2010 Jan 1;28(1):92-8 PMID: 19933921
  35. Meta-analysis for cyclin E in lung cancer survival.
    Clin Chim Acta. 2012 Apr 11;413(7-8):663-8 PMID: 22244930
  36. Epidermal growth factor receptor and HER2-neu mRNA expression in non-small cell lung cancer Is correlated with survival.
    Clin Cancer Res. 2001 Jul;7(7):1850-5 PMID: 11448895
  37. Lung adjuvant cisplatin evaluation: a pooled analysis by the LACE Collaborative Group.
    J Clin Oncol. 2008 Jul 20;26(21):3552-9 PMID: 18506026
  38. ERCC1 expression is a predictor of survival in resected patients with non-small cell lung cancer.
    Chest. 2005 Mar;127(3):978-83 PMID: 15764785
  39. Prognostic value of matrix metalloproteinase 9 expression in patients with non-small cell lung cancer.
    Clin Chim Acta. 2012 Jul 11;413(13-14):1121-6 PMID: 22465234
  40. Cyclin D1, p16 and retinoblastoma gene product expression as a predictor for prognosis in non-small cell lung cancer at stages I and II.
    Lung Cancer. 2001 Nov;34(2):207-18 PMID: 11679179
  41. RecurrenceOnline: an online analysis tool to determine breast cancer recurrence and hormone receptor status using microarray data.
    Breast Cancer Res Treat. 2012 Apr;132(3):1025-34 PMID: 21773767
  42. Interferon (alpha, beta and omega) receptor 2 is a prognostic biomarker for lung cancer.
    Pathobiology. 2012;79(1):24-33 PMID: 22236545
  43. Correlation of KAI1/CD82 gene expression with good prognosis in patients with non-small cell lung cancer.
    Cancer Res. 1996 Apr 15;56(8):1751-5 PMID: 8620488
  44. XAF1 as a prognostic biomarker and therapeutic target in squamous cell lung cancer.
    Chin Med J (Engl). 2011 Oct;124(20):3238-43 PMID: 22088514
  45. Osteopontin but not osteonectin messenger RNA expression is a prognostic marker in curatively resected non-small cell lung cancer.
    Clin Cancer Res. 2004 Mar 1;10(5):1588-96 PMID: 15014008
  46. Robust gene expression signature from formalin-fixed paraffin-embedded samples predicts prognosis of non-small-cell lung cancer patients.
    Clin Cancer Res. 2011 Sep 1;17(17):5705-14 PMID: 21742808
  47. Prognostic and predictive gene signature for adjuvant chemotherapy in resected non-small-cell lung cancer.
    J Clin Oncol. 2010 Oct 10;28(29):4417-24 PMID: 20823422
  48. Evaluation of microarray preprocessing algorithms based on concordance with RT-PCR in clinical samples.
    PLoS One. 2009 May 21;4(5):e5645 PMID: 19461970
Article Info
Journal
PloS one
Abbr.
PLoS One
ISSN
1932-6203
Published
2013-00-00
Epub
2013-00-18
Pages
e82241
Language
English
Region
United States
NLM ID
101285081
PMCID
PMC3867325
Subset
IM
Corrections
ErratumIn
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