PMID- 19996206
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220318
IS  - 1557-3265 (Electronic)
IS  - 1078-0432 (Print)
IS  - 1078-0432 (Linking)
VI  - 15
IP  - 24
DP  - 2009 Dec 15
TI  - Metastasis-Associated Gene Expression Changes Predict Poor Outcomes in Patients 
      with Dukes Stage B and C Colorectal Cancer.
PG  - 7642-7651
AB  - PURPOSE: Colorectal cancer prognosis is currently predicted from pathologic 
      staging, providing limited discrimination for Dukes stage B and C disease. 
      Additional markers for outcome are required to help guide therapy selection for 
      individual patients. EXPERIMENTAL DESIGN: A multisite single-platform microarray 
      study was done on 553 colorectal cancers. Gene expression changes were identified 
      between stage A and D tumors (three training sets) and assessed as a prognosis 
      signature in stage B and C tumors (independent test and external validation 
      sets). RESULTS: One hundred twenty-eight genes showed reproducible expression 
      changes between three sets of stage A and D cancers. Using consistent genes, 
      stage B and C cancers clustered into two groups resembling early-stage and 
      metastatic tumors. A Prediction Analysis of Microarray algorithm was developed to 
      classify individual intermediate-stage cancers into stage A-like/good prognosis 
      or stage D-like/poor prognosis types. For stage B patients, the treatment 
      adjusted hazard ratio for 6-year recurrence in individuals with stage D-like 
      cancers was 10.3 (95% confidence interval, 1.3-80.0; P = 0.011). For stage C 
      patients, the adjusted hazard ratio was 2.9 (95% confidence interval, 1.1-7.6; P 
      = 0.016). Similar results were obtained for an external set of stage B and C 
      patients. The prognosis signature was enriched for downregulated immune response 
      genes and upregulated cell signaling and extracellular matrix genes. Accordingly, 
      sparse tumor infiltration with mononuclear chronic inflammatory cells was 
      associated with poor outcome in independent patients. CONCLUSIONS: 
      Metastasis-associated gene expression changes can be used to refine traditional 
      outcome prediction, providing a rational approach for tailoring treatments to 
      subsets of patients. (Clin Cancer Res 2009;15(24):7642-51).
FAU - Jorissen, Robert N
AU  - Jorissen RN
AD  - Authors' Affiliations: Ludwig Colon Cancer Initiative Laboratory, Ludwig 
      Institute for Cancer Research; Anatomic Pathology Department, Royal Melbourne 
      Hospital, Parkville, Victoria, Australia; Department of Clinical Pharmacology, 
      University of Oxford, Oxford, United Kingdom; Department of Medical Genetics, 
      Biomedicum, University of Helsinki, Helsinki, Finland; Group of Molecular 
      Oncology, Nanomedicine Research Program, Molecular Biology and Biochemistry 
      Research Center (Centro de Investigacion Bioquimica y Biologia Molecular), Vall 
      d'Hebron Hospital Research Institute, Barcelona, Spain; Molecular Diagnostic 
      Laboratory, Department of Clinical Biochemistry, Aarhus University Hospital, 
      Skejby, Denmark; and GI Surgical Oncology, H. Lee Moffitt Cancer Center and 
      Research Institute, Tampa, Florida.
FAU - Gibbs, Peter
AU  - Gibbs P
FAU - Christie, Michael
AU  - Christie M
FAU - Prakash, Saurabh
AU  - Prakash S
FAU - Lipton, Lara
AU  - Lipton L
FAU - Desai, Jayesh
AU  - Desai J
FAU - Kerr, David
AU  - Kerr D
FAU - Aaltonen, Lauri A
AU  - Aaltonen LA
FAU - Arango, Diego
AU  - Arango D
FAU - Kruhoffer, Mogens
AU  - Kruhoffer M
FAU - Orntoft, Torben F
AU  - Orntoft TF
FAU - Andersen, Claus Lindbjerg
AU  - Andersen CL
FAU - Gruidl, Mike
AU  - Gruidl M
FAU - Kamath, Vidya P
AU  - Kamath VP
FAU - Eschrich, Steven
AU  - Eschrich S
FAU - Yeatman, Timothy J
AU  - Yeatman TJ
FAU - Sieber, Oliver M
AU  - Sieber OM
LA  - eng
GR  - R01 CA112215/CA/NCI NIH HHS/United States
GR  - R01 CA112215-01A2/CA/NCI NIH HHS/United States
PT  - Journal Article
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
PMC - PMC2920750
MID - NIHMS145205
EDAT- 2009/12/10 06:00
MHDA- 2009/12/10 06:01
PMCR- 2010/12/01
CRDT- 2009/12/10 06:00
PHST- 2009/12/10 06:00 [entrez]
PHST- 2009/12/10 06:00 [pubmed]
PHST- 2009/12/10 06:01 [medline]
PHST- 2010/12/01 00:00 [pmc-release]
AID - 1078-0432.CCR-09-1431 [pii]
AID - 10.1158/1078-0432.CCR-09-1431 [doi]
PST - ppublish
SO  - Clin Cancer Res. 2009 Dec 15;15(24):7642-7651. doi: 
      10.1158/1078-0432.CCR-09-1431.