PMID- 23032747
OWN - NLM
STAT- MEDLINE
DCOM- 20130618
LR  - 20220410
IS  - 1557-3265 (Electronic)
IS  - 1078-0432 (Linking)
VI  - 19
IP  - 1
DP  - 2013 Jan 1
TI  - Biomarker discovery in non-small cell lung cancer: integrating gene expression 
      profiling, meta-analysis, and tissue microarray validation.
PG  - 194-204
LID - 10.1158/1078-0432.CCR-12-1139 [doi]
AB  - 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.
FAU - Botling, Johan
AU  - Botling J
AD  - Departments of Immunology, Genetics and Pathology, Uppsala University, Uppsala, 
      Sweden.
FAU - Edlund, Karolina
AU  - Edlund K
FAU - Lohr, Miriam
AU  - Lohr M
FAU - Hellwig, Birte
AU  - Hellwig B
FAU - Holmberg, Lars
AU  - Holmberg L
FAU - Lambe, Mats
AU  - Lambe M
FAU - Berglund, Anders
AU  - Berglund A
FAU - Ekman, Simon
AU  - Ekman S
FAU - Bergqvist, Michael
AU  - Bergqvist M
FAU - Ponten, Fredrik
AU  - Ponten F
FAU - Konig, Andre
AU  - Konig A
FAU - Fernandes, Oswaldo
AU  - Fernandes O
FAU - Karlsson, Mats
AU  - Karlsson M
FAU - Helenius, Gisela
AU  - Helenius G
FAU - Karlsson, Christina
AU  - Karlsson C
FAU - Rahnenfuhrer, Jorg
AU  - Rahnenfuhrer J
FAU - Hengstler, Jan G
AU  - Hengstler JG
FAU - Micke, Patrick
AU  - Micke P
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20121002
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (CADM1 protein, human)
RN  - 0 (Cell Adhesion Molecule-1)
RN  - 0 (Cell Adhesion Molecules)
RN  - 0 (Immunoglobulins)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Biomarkers, Tumor/*genetics
MH  - Carcinoma, Non-Small-Cell Lung/*genetics/mortality/pathology
MH  - Cell Adhesion Molecule-1
MH  - Cell Adhesion Molecules/genetics/metabolism
MH  - Cluster Analysis
MH  - Female
MH  - *Gene Expression Profiling
MH  - *Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Immunoglobulins/genetics/metabolism
MH  - Lung Neoplasms/*genetics/mortality/pathology
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Staging
MH  - Prognosis
MH  - Reproducibility of Results
EDAT- 2012/10/04 06:00
MHDA- 2013/06/19 06:00
CRDT- 2012/10/04 06:00
PHST- 2012/10/04 06:00 [entrez]
PHST- 2012/10/04 06:00 [pubmed]
PHST- 2013/06/19 06:00 [medline]
AID - 1078-0432.CCR-12-1139 [pii]
AID - 10.1158/1078-0432.CCR-12-1139 [doi]
PST - ppublish
SO  - Clin Cancer Res. 2013 Jan 1;19(1):194-204. doi: 10.1158/1078-0432.CCR-12-1139. 
      Epub 2012 Oct 2.