Tissue array analysis of expression microarray candidates identifies markers associated with tumor grade and outcome in serous epithelial ovarian cancer.
Molecular profiling is a powerful approach to identify potential clinical markers for diagnosis and prognosis as well as providing a better understanding of the biology of epithelial ovarian cancer. On the basis of the analysis of HuFL expression data, we have previously identified genes that distinguish low malignant potential and invasive serous epithelial ovarian tumors. In this study, we used immunohistochemistry to monitor a subset of differently expressed candidates (Ahr, Paep, Madh3, Ran, Met, Mek1, Ccne1, Ccd20, Cks1 and Cas). A tissue array composed of 244 serous tumors of different grades (0-3) and stages (I-IV) was used in this analysis. All markers assayed presented differential protein expression between serous tumors of low and high grade. Significant differences in Ccne1 and Ran expression were observed in a comparison of low malignant potential and grade 1 tumor samples (p<0.01). In addition, irrespective of the grade, Ccne1, Ran, Cdc20 and Cks1 showed significant differences of expression in association with the clinical stage of disease. While high level of Ccne1 have previously been associated with poor outcomes, here we found that high level of either Ran or Cdc20 appear to be more tightly associated with a poor prognosis (p<0.001, 0.03, respectively). The application of these biomarkers in both the initial diagnosis and prognostic attributes of patients with epithelial ovarian tumors should prove to be useful in patient management.
Ouellet
Véronique
V
Centre de Recherche du Centre hospitalier de l'Université de Montréal/ Institut du cancer de Montréal, Montreal, Canada.
Guyot
Marie-Claude
MC
Le Page
Cécile
C
Filali-Mouhim
Abdelali
A
Lussier
Christian
C
Tonin
Patricia N
PN
Provencher
Diane M
DM
Mes-Masson
Anne-Marie
AM
D051792:Basic Helix-Loop-Helix Proteins; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D042846:CDC2-CDC28 Kinases; D002352:Carrier Proteins / Q000032:analysis / Q000235:genetics; D064199:Cdc20 Proteins; D018797:Cell Cycle Proteins / Q000032:analysis / Q000235:genetics; D029563:Cellular Apoptosis Susceptibility Protein / Q000032:analysis / Q000235:genetics; D019927:Cyclin E / Q000032:analysis / Q000235:genetics; D018844:Cyclin-Dependent Kinases / Q000032:analysis / Q000235:genetics; D018284:Cystadenocarcinoma, Serous / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D005260:Female; D020869:Gene Expression Profiling; D000071816:Glycodelin; D006023:Glycoproteins / Q000032:analysis / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D048369:MAP Kinase Kinase 1 / Q000032:analysis / Q000235:genetics; D008875:Middle Aged; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D015513:Oncogene Proteins / Q000032:analysis / Q000235:genetics; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D011257:Pregnancy Proteins / Q000032:analysis / Q000235:genetics; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000235:genetics; D019859:Proto-Oncogene Proteins c-met; D018336:Receptors, Aryl Hydrocarbon / Q000032:analysis / Q000235:genetics; D017978:Receptors, Growth Factor / Q000032:analysis / Q000235:genetics; D051900:Smad3 Protein / Q000032:analysis / Q000235:genetics; D016019:Survival Analysis; D046888:Tissue Array Analysis / Q000379:methods*; D020931:ran GTP-Binding Protein / Q000032:analysis / Q000235:genetics
D051792:Basic Helix-Loop-Helix Proteins; D014408:Biomarkers, Tumor; D042846:CDC2-CDC28 Kinases; D002352:Carrier Proteins; D064199:Cdc20 Proteins; D018797:Cell Cycle Proteins; D029563:Cellular Apoptosis Susceptibility Protein; D019927:Cyclin E; D018844:Cyclin-Dependent Kinases; D000071816:Glycodelin; D006023:Glycoproteins; D048369:MAP Kinase Kinase 1; D015513:Oncogene Proteins; D011257:Pregnancy Proteins; D011518:Proto-Oncogene Proteins; D019859:Proto-Oncogene Proteins c-met; D018336:Receptors, Aryl Hydrocarbon; D017978:Receptors, Growth Factor; D051900:Smad3 Protein; D020931:ran GTP-Binding Protein; C111235:AHR protein, human; C475820:CCNE1 protein, human; C093090:CKS1B protein, human; C045246:PAEP protein, human; C120587:RAN protein, human; C497790:SMAD3 protein, human; C577488:CDC20 protein, human; C491743:MET protein, human; C482125:MAP2K1 protein, human