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COL11A1 promotes tumor progression and predicts poor clinical outcome in ovarian cancer.

GSE44104_eset.Rd

Biomarkers that predict disease progression might assist the development of better therapeutic strategies for aggressive cancers, such as ovarian cancer. Here, we investigated the role of collagen type XI alpha 1 (COL11A1) in cell invasiveness and tumor formation and the prognostic impact of COL11A1 expression in ovarian cancer. Microarray analysis suggested that COL11A1 is a disease progression-associated gene that is linked to ovarian cancer recurrence and poor survival. Small interference RNA-mediated specific reduction in COL11A1 protein levels suppressed the invasive ability and oncogenic potential of ovarian cancer cells and decreased tumor formation and lung colonization in mouse xenografts. A combination of experimental approaches, including real-time RT-PCR, casein zymography and chromatin immunoprecipitation (ChIP) assays, showed that COL11A1 knockdown attenuated MMP3 expression and suppressed binding of Ets-1 to its putative MMP3 promoter-binding site, suggesting that the Ets-1-MMP3 axis is upregulated by COL11A1. Transforming growth factor (TGF)-beta (TGF-??1) treatment triggers the activation of smad2 signaling cascades, leading to activation of COL11A1 and MMP3. Pharmacological inhibition of MMP3 abrogated the TGF-??1-triggered, COL11A1-dependent cell invasiveness. Furthermore, the NF-YA-binding site on the COL11A1 promoter was identified as the major determinant of TGF-??1-dependent COL11A1 activation. Analysis of 88 ovarian cancer patients indicated that high COL11A1 mRNA levels are associated with advanced disease stage. The 5-year recurrence-free and overall survival rates were significantly lower (P=0.006 and P=0.018, respectively) among patients with high expression levels of tissue COL11A1 mRNA compared with those with low expression. We conclude that COL11A1 may promote tumor aggressiveness via the TGF-??1-MMP3 axis and that COL11A1 expression can predict clinical outcome in ovarian cancer patients.

Usage

data( GSE44104_eset )

Format


experimentData(eset):
Experiment data
  Experimenter name: Wu Y, Chang T, Huang Y, Huang H, Chou C
  Laboratory: Wu, Chou 2013
  Contact information:
  Title: COL11A1 promotes tumor progression and predicts poor clinical outcome in ovarian cancer.
  URL:
  PMIDs: 23934190

  Abstract: A 260 word abstract is available. Use 'abstract' method.
  Information is available on: preprocessing
  notes:
   platform_title:
      [HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array
   platform_shorttitle:
      Affymetrix HG-U133Plus2
   platform_summary:
      hgu133plus2
   platform_manufacturer:
      Affymetrix
   platform_distribution:
      commercial
   platform_accession:
      GPL570
   platform_technology:
      in situ oligonucleotide

Preprocessing: frma
featureData(eset):
An object of class 'AnnotatedDataFrame'
  featureNames: A1BG A1BG-AS1 ... ZZZ3 (19816 total)
  varLabels: probeset gene
  varMetadata: labelDescription

Details


assayData: 19816 features, 60 samples
Platform type: hgu133plus2
Binary overall survival summary (definitions of long and short provided by study authors):

 long short
   44    16

---------------------------
Available sample meta-data:
---------------------------

alt_sample_name:
   Length     Class      Mode
       60 character character

sample_type:
tumor
   60

histological_type:
clearcell      endo  mucinous       ser
       12        11         9        28

summarystage:
early  late
   25    35

tumorstage:
 1  2  3  4
17  8 30  5

recurrence_status:
norecurrence   recurrence
          40           20

os_binary:
 long short
   44    16

relapse_binary:
 long short
   40    20

batch:
2010-09-07 2010-09-08 2010-10-14 2010-12-10 2010-12-14
        20          2         18         16          4

uncurated_author_metadata:
   Length     Class      Mode
       60 character character