title: Cross-validation of survival associated biomarkers in gastric cancer using transcriptomic data of 1,065 patients.
abstract: BACKGROUND
  Multiple gene expression based prognostic biomarkers have been repeatedly identified in gastric carcinoma. However, without confirmation in an independent validation study, their clinical utility is limited. Our goal was to establish a robust database enabling the swift validation of previous and future gastric cancer survival biomarker candidates.
  
  
  RESULTS
  The entire database incorporates 1,065 gastric carcinoma samples, gene expression data. Out of 29 established markers, higher expression of BECN1 (HR = 0.68, p = 1.5E-05), CASP3 (HR = 0.5, p = 6E-14), COX2 (HR = 0.72, p = 0.0013), CTGF (HR = 0.72, p = 0.00051), CTNNB1 (HR = 0.47, p = 4.3E-15), MET (HR = 0.63, p = 1.3E-05), and SIRT1 (HR = 0.64, p = 2.2E-07) correlated to longer OS. Higher expression of BIRC5 (HR = 1.45, p = 1E-04), CNTN1 (HR = 1.44, p = 3.5E- 05), EGFR (HR = 1.86, p = 8.5E-11), ERCC1 (HR = 1.36, p = 0.0012), HER2 (HR = 1.41, p = 0.00011), MMP2 (HR = 1.78, p = 2.6E-09), PFKB4 (HR = 1.56, p = 3.2E-07), SPHK1 (HR = 1.61, p = 3.1E-06), SP1 (HR = 1.45, p = 1.6E-05), TIMP1 (HR = 1.92, p = 2.2E- 10) and VEGF (HR = 1.53, p = 5.7E-06) were predictive for poor OS.
  
  
  METHODS
  We integrated samples of three major cancer research centers (Berlin, Bethesda and Melbourne datasets) and publicly available datasets with available follow-up data to form a single integrated database. Subsequently, we performed a literature search for prognostic markers in gastric carcinomas (PubMed, 2012-2015) and re-validated their findings predicting first progression (FP) and overall survival (OS) using uni- and multivariate Cox proportional hazards regression analysis.
  
  
  CONCLUSIONS
  The major advantage of our analysis is that we evaluated all genes in the same set of patients thereby making direct comparison of the markers feasible. The best performing genes include BIRC5, CASP3, CTNNB1, TIMP-1, MMP-2, SIRT, and VEGF.
authors.affiliation: MTA-TTK Lendület Cancer Biomarker Research Group, Budapest, Hungary.|2nd Department of Pathology, Semmelweis University, Budapest, Hungary.
authors.forename: A Marcell
authors.initials: AM
authors.lastname: Szász
authors.affiliation: MTA-TTK Lendület Cancer Biomarker Research Group, Budapest, Hungary.
authors.forename: András
authors.initials: A
authors.lastname: Lánczky
authors.affiliation: MTA-TTK Lendület Cancer Biomarker Research Group, Budapest, Hungary.
authors.forename: Ádám
authors.initials: Á
authors.lastname: Nagy
authors.affiliation: Max Delbrück Center for Molecular Medicine, Berlin, Germany.
authors.forename: Susann
authors.initials: S
authors.lastname: Förster
authors.affiliation: Transgenic Oncogenesis and Genomics Section, Laboratory of Cancer Biology and Genetics, National Cancer Institute, Bethesda, Maryland, USA.
authors.forename: Kim
authors.initials: K
authors.lastname: Hark
authors.affiliation: Transgenic Oncogenesis and Genomics Section, Laboratory of Cancer Biology and Genetics, National Cancer Institute, Bethesda, Maryland, USA.
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Green
authors.affiliation: Cancer Genetics and Genomics Laboratory, Peter MacCallum Cancer Centre, East Melbourne, Australia.|Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Australia.|Department of Medicine, Royal Melbourne Hospital, The University of Melbourne, Melbourne, Australia.
authors.forename: Alex
authors.initials: A
authors.lastname: Boussioutas
authors.affiliation: Cancer Genetics and Genomics Laboratory, Peter MacCallum Cancer Centre, East Melbourne, Australia.|Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Australia.|Department of Medicine, Royal Melbourne Hospital, The University of Melbourne, Melbourne, Australia.
authors.forename: Rita
authors.initials: R
authors.lastname: Busuttil
authors.affiliation: 2nd Department of Pediatrics, Semmelweis University, Budapest, Hungary.
authors.forename: András
authors.initials: A
authors.lastname: Szabó
authors.affiliation: MTA-TTK Lendület Cancer Biomarker Research Group, Budapest, Hungary.|2nd Department of Pediatrics, Semmelweis University, Budapest, Hungary.
authors.forename: Balázs
authors.initials: B
authors.lastname: Győrffy
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D016016:Proportional Hazards Models; D056564:Sirtuin 1 / Q000378:metabolism; D013274:Stomach Neoplasms / Q000378:metabolism*; D000077022:Survivin; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D059467:Transcriptome; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
chemical_list: C107489:BIRC5 protein, human; D014408:Biomarkers, Tumor; C495270:CTNNB1 protein, human; D051034:Inhibitor of Apoptosis Proteins; D000077022:Survivin; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D051176:beta Catenin; C505407:CASP3 protein, human; D053148:Caspase 3; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C447939:SIRT1 protein, human; D056564:Sirtuin 1
keywords: gastric cancer; meta-analysis; survival