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  • Botling, JohanUppsala universitet,Molekylär och morfologisk patologi,Botling (author)

Biomarker Discovery in Non-Small Cell Lung Cancer : Integrating Gene Expression Profiling, Meta-analysis, and Tissue Microarray Validation

  • Article/chapterEnglish2013

Publisher, publication year, extent ...

  • 2013
  • printrdacarrier

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  • LIBRIS-ID:oai:DiVA.org:oru-38714
  • https://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-38714URI
  • https://doi.org/10.1158/1078-0432.CCR-12-1139DOI
  • https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-120037URI
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-183399URI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:125896989URI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • Funding agencies are:Swedish Cancer Society  Lions Cancer Foundation, Uppsala, Sweden  German Research Foundation (DFG) RA 870/4-1, RA 870/5-1 Astra Zeneca  Knut and Alice Wallenberg Foundation 
  • Purpose: Global gene expression profiling has been widely used in lung cancer research to identify clinically relevant molecular subtypes as well as to predict prognosis and therapy response. So far, the value of these multigene signatures in clinical practice is unclear, and the biologic importance of individual genes is difficult to assess, as the published signatures virtually do not overlap.Experimental Design: Here, we describe a novel single institute cohort, including 196 non-small lung cancers (NSCLC) with clinical information and long-term follow-up. Gene expression array data were used as a training set to screen for single genes with prognostic impact. The top 450 probe sets identified using a univariate Cox regression model (significance level P < 0.01) were tested in a meta-analysis including five publicly available independent lung cancer cohorts (n = 860).Results: The meta-analysis revealed 14 genes that were significantly associated with survival (P < 0.001) with a false discovery rate < 1%. The prognostic impact of one of these genes, the cell adhesion molecule 1 (CADM1), was confirmed by use of immunohistochemistry on tissue microarrays from 2 independent NSCLC cohorts, altogether including 617 NSCLC samples. Low CADM1 protein expression was significantly associated with shorter survival, with particular influence in the adenocarcinoma patient subgroup.Conclusions: Using a novel NSCLC cohort together with a meta-analysis validation approach, we have identified a set of single genes with independent prognostic impact. One of these genes, CADM1, was further established as an immunohistochemical marker with a potential application in clinical diagnostics. Clin Cancer Res; 19(1); 194-204. (c) 2012 AACR.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Edlund, KarolinaUppsala universitet,Molekylär och morfologisk patologi,Botling(Swepub:uu)kaedl086 (author)
  • Lohr, MiriamDepartment of Statistics, TU Dortmund University, Dortmund, Germany (author)
  • Hellwig, BirteDepartment of Statistics, TU Dortmund University, Dortmund, Germany (author)
  • Holmberg, LarsUppsala universitet,Endokrinkirurgi(Swepub:uu)larsholmb (author)
  • Lambe, Mats G.Karolinska Institutet (author)
  • Berglund, AndersUppsala universitet,Endokrinkirurgi(Swepub:uu)andbe182 (author)
  • Ekman, SimonUppsala universitet,Enheten för onkologi(Swepub:uu)simoekma (author)
  • Bergqvist, MichaelUppsala universitet,Enheten för onkologi(Swepub:uu)michberg (author)
  • Pontén, FredrikUppsala universitet,Molekylär och morfologisk patologi,Pontén(Swepub:uu)fredpont (author)
  • König, AndréDepartment of Statistics, TU Dortmund University, Dortmund, Germany (author)
  • Fernandes, OswaldoCardiothoracic Surgery, Örebro University Hospital, Örebro, Sweden (author)
  • Karlsson, MatsRegion Örebro län,Laboratory Medicine(Swepub:oru)mskn (author)
  • Helenius, GiselaRegion Örebro län,Laboratory Medicine(Swepub:oru)ghs (author)
  • Karlsson, Christina,1968-Örebro universitet, Institutionen för hälsovetenskap och medicin(Swepub:oru)ckn (author)
  • Rahnenfuehrer, JörgDepartment of Statistics, TU Dortmund University, Dortmund, Germany (author)
  • Hengstler, Jan G.Leibniz Research Centre for Working Environment and Human Factors (IfADo), Dortmund, Germany (author)
  • Micke, PatrickUppsala universitet,Molekylär och morfologisk patologi,Botling(Swepub:uu)patmi676 (author)
  • Uppsala universitetMolekylär och morfologisk patologi (creator_code:org_t)

Related titles

  • In:Clinical Cancer Research19:1, s. 194-2041078-04321557-3265

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