Gene expression profiling of primary cultures of ovarian epithelial cells identifies novel molecular classifiers of ovarian cancer.
In order to elucidate the biological variance between normal ovarian surface epithelial (NOSE) and epithelial ovarian cancer (EOC) cells, and to build a molecular classifier to discover new markers distinguishing these cells, we analysed gene expression patterns of 65 primary cultures of these tissues by oligonucleotide microarray. Unsupervised clustering highlights three subgroups of tumours: low malignant potential tumours, invasive solid tumours and tumour cells derived from ascites. We selected 18 genes with expression profiles that enable the distinction of NOSE from these three groups of EOC with 92% accuracy. Validation using an independent published data set derived from tissues or primary cultures confirmed a high accuracy (87-96%). The distinctive expression pattern of a subset of genes was validated by quantitative reverse transcription-PCR. An ovarian-specific tissue array representing tissues from NOSE and EOC samples of various subtypes and grades was used to further assess the protein expression patterns of two differentially expressed genes (Msln and BMP-2) by immunohistochemistry. This study highlights the relevance of using primary cultures of epithelial ovarian cells as a model system for gene profiling studies and demonstrates that the statistical analysis of gene expression profiling is a useful approach for selecting novel molecular tumour markers.
Le Page
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C
Centre de Recherche of the Center hospitalier de l'Université de Montréal (CR-CHUM)/Institut du cancer de Montréal, Montreal, Quebec, Canada H2L 4M1.
Ouellet
V
V
Madore
J
J
Ren
F
F
Hudson
T J
TJ
Tonin
P N
PN
Provencher
D M
DM
Mes-Masson
A-M
AM
D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000032:analysis / Q000235:genetics; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000166:cytology / Q000473:pathology; D005260:Female; D058851:GPI-Linked Proteins; D020869:Gene Expression Profiling; D052138:Genes, Neoplasm; D006801:Humans; D008562:Membrane Glycoproteins / Q000032:analysis / Q000235:genetics; D000090204:Mesothelin; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000145:classification* / Q000175:diagnosis* / Q000235:genetics; D010053:Ovary / Q000737:chemistry / Q000166:cytology / Q000473:pathology; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000032:analysis / Q000235:genetics; D000254:Sodium-Potassium-Exchanging ATPase / Q000032:analysis / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000235:genetics; D014407:Tumor Cells, Cultured
C503551:ATP1B1 protein, human; C525718:BMP2 protein, human; D014408:Biomarkers, Tumor; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D058851:GPI-Linked Proteins; C000715527:MSLN protein, human; D008562:Membrane Glycoproteins; D047888:Receptors, Tumor Necrosis Factor, Type I; D016212:Transforming Growth Factor beta; D000254:Sodium-Potassium-Exchanging ATPase; D000090204:Mesothelin