title: Molecular markers associated with nonepithelial ovarian cancer in formalin-fixed, paraffin-embedded specimens by genome wide expression profiling.
abstract: Nonepithelial ovarian cancer (NEOC) is a rare cancer that is often misdiagnosed as other malignant tumors. Research on this cancer using fresh tissues is nearly impossible because of its limited number of samples within a limited time provided. The study is to identify potential genes and their molecular pathways related to NEOC using formalin-fixed paraffin embedded samples. Total RNA was extracted from eight archived NEOCs and seven normal ovaries. The RNA samples with RNA integrity number >2.0, purity >1.7 and cycle count value <28 cycles were hybridized to the Illumina Whole-Genome DASL assay (cDNA-mediated annealing, selection, extension, and ligation). We analyzed the results using the GeneSpring GX11.0 and FlexArray software to determine the differentially expressed genes. Microarray results were validated using an immunohistochemistry method. Statistical analysis identified 804 differentially expressed genes with 443 and 361 genes as overexpressed and underexpressed in cancer, respectively. Consistent findings were documented for the overexpression of eukaryotic translation elongation factor 1 alpha 1, E2F transcription factor 2, and fibroblast growth factor receptor 3, except for the down-regulated gene, early growth response 1 (EGR1). The immunopositivity staining for EGR1 was found in the majority of cancer tissues. This finding suggested that the mRNA level of a transcript did not always match with the protein expression in tissues. The current gene profile can be the platform for further exploration of the molecular mechanism of NEOC.
authors.affiliation: Department of Physiology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.
authors.forename: Koon
authors.initials: K
authors.lastname: Vui-Kee
authors.forename: Ahmad Zailani Hatta
authors.initials: AZ
authors.lastname: Mohd Dali
authors.forename: Isa
authors.initials: I
authors.lastname: Mohamed Rose
authors.forename: Razmin
authors.initials: R
authors.lastname: Ghazali
authors.forename: Rahman
authors.initials: R
authors.lastname: Jamal
authors.forename: Norfilza Mohd
authors.initials: NM
authors.lastname: Mokhtar
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D050703:E2F2 Transcription Factor / Q000235:genetics*; D051766:Early Growth Response Protein 1 / Q000235:genetics*; D005260:Female; D005404:Fixatives; D005557:Formaldehyde; D015972:Gene Expression Regulation, Neoplastic; D015894:Genome, Human; D055106:Genome-Wide Association Study; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D010051:Ovarian Neoplasms / Q000175:diagnosis / Q000235:genetics; D016612:Paraffin Embedding; D020648:Peptide Elongation Factor 1 / Q000235:genetics*; D012334:RNA, Neoplasm / Q000096:biosynthesis*; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D050703:E2F2 Transcription Factor; C493761:E2F2 protein, human; C094814:EEF1A1 protein, human; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D005404:Fixatives; D020648:Peptide Elongation Factor 1; D012334:RNA, Neoplasm; D005557:Formaldehyde; D051498:Receptor, Fibroblast Growth Factor, Type 3