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.

Initiation and elongation factor co-expression correlates with recurrence and survival in epithelial ovarian cancer

“…These events occur as a response to the tumour microenvironment, immunological changes and their proliferation [ 20 ]. The subunits involved in the translational machinery of OC in tumour tissue or cell lines has been reported for eIF6 [ 13 , 14 , 21 , 22 ], eIF5A [ 23 – 26 ], eIF5B [ 27 ], eEF1 [ 28 – 30 ] and eIF2α [ 31 – 36 ]. No reports were found to have directly assessed eIF2G (or synonym eIF2S3) for OC.…”

“…For eEF1A, interestingly, a gene expression study on non-epithelial ovarian cancer (granulosa cell tumor, mixed germ cell tumor, yolk sac tumour, immature teratoma, malignant mature teratoma, dysgerminoma, thecoma and juvenile granulosa cell tumor) was performed to compare expression with normal ovarian tissue. It was shown that cytoplasmic expression of eEF1A was increased in non-epithelial ovarian cancer [ 28 ]. Furthermore, it was shown that eEF1A2 overexpression was present in 75% of clear cell carcinomas, which is higher than in other histological subtypes [ 29 ].…”

Genomic Expression Profiles: From Molecular Signatures to Clinical Oncology Translation

“…Despite its rare incidence of this subtype of ovarian cancer, we have performed microarray assay on the formalin-fixed paraffin embedded tissues (63). About 804 differentially expressed genes with at least 2-fold change (P<0.005) (63).…”