Biomarker discovery in non-small cell lung cancer: integrating gene expression profiling, meta-analysis and tissue microarray validation
2013 (English)In: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 19, no 1, 194-204 p.Article in journal (Refereed) Published
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 multi-gene signatures in clinical practice is unclear and the biological importance of individual genes is difficult to assess as the published signatures virtually do not overlap
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 was 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).
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 two 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.
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.
Place, publisher, year, edition, pages
2013. Vol. 19, no 1, 194-204 p.
Clinical Laboratory Medicine
Research subject Pathology
IdentifiersURN: urn:nbn:se:uu:diva-183399DOI: 10.1158/1078-0432.CCR-12-1139ISI: 000313051100021PubMedID: 23032747OAI: oai:DiVA.org:uu-183399DiVA: diva2:562657