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.
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 adenocarcinomapatient 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.
Authors: Yulong Chen; Masahiko Terajima; Yanan Yang; Li Sun; Young-Ho Ahn; Daniela Pankova; Daniel S Puperi; Takeshi Watanabe; Min P Kim; Shanda H Blackmon; Jaime Rodriguez; Hui Liu; Carmen Behrens; Ignacio I Wistuba; Rosalba Minelli; Kenneth L Scott; Johannah Sanchez-Adams; Farshid Guilak; Debananda Pati; Nishan Thilaganathan; Alan R Burns; Chad J Creighton; Elisabeth D Martinez; Tomasz Zal; K Jane Grande-Allen; Mitsuo Yamauchi; Jonathan M Kurie Journal: J Clin Invest Date: 2015-02-09 Impact factor: 14.808
Authors: Lu Chen; Brienne E Engel; Eric A Welsh; Sean J Yoder; Stephen G Brantley; Dung-Tsa Chen; Amer A Beg; Chunxia Cao; Frederic J Kaye; Eric B Haura; Matthew B Schabath; W Douglas Cress Journal: J Thorac Oncol Date: 2016-02-23 Impact factor: 15.609
Authors: Yanan Yang; Young-Ho Ahn; Yulong Chen; Xiaochao Tan; Lixia Guo; Don L Gibbons; Christin Ungewiss; David H Peng; Xin Liu; Steven H Lin; Nishan Thilaganathan; Ignacio I Wistuba; Jaime Rodriguez-Canales; Georgia McLendon; Chad J Creighton; Jonathan M Kurie Journal: J Clin Invest Date: 2014-04-24 Impact factor: 14.808
Authors: Dijana Djureinovic; Björn M Hallström; Masafumi Horie; Johanna Sofia Margareta Mattsson; Linnea La Fleur; Linn Fagerberg; Hans Brunnström; Cecilia Lindskog; Katrin Madjar; Jörg Rahnenführer; Simon Ekman; Elisabeth Ståhle; Hirsh Koyi; Eva Brandén; Karolina Edlund; Jan G Hengstler; Mats Lambe; Akira Saito; Johan Botling; Fredrik Pontén; Mathias Uhlén; Patrick Micke Journal: JCI Insight Date: 2016-07-07