Abstract
BackgroundIn the Western world, endometrial cancers are the most common gynaecological neoplastic disorders among women. Initial symptoms are often vague and may be confused with several other conditions or disorders. Thus, there is a need for an easy and reliable diagnostic tool. The objective of this work was to identify a gene expression signature specific for endometrial adenocarcinomas to be used for testing potential endometrial biomarkers.ResultsChanges in expression between endometrial adenocarcinomas and non-/pre-malignant endometrium from the BDII EAC rat model were compared in cDNA microarray assays. By employing classification analysis (Weka) on the expression data from approximately 5600 cDNA clones and TDT analysis on genotype data, we identified a three-gene signature (Gpx3, Bgn and Tgfb3). An independent analysis of differential expression, revealed a total of 354 cDNA clones with significant changes in expression. Among the 10 best ranked clones, Gpx3, Bgn and Tgfb3 were found.ConclusionTaken together, we present a unique data set of genes with different expression patterns between EACs and non-/pre-malignant endometrium, and specifically we found three genes that were confirmed in two independent analyses. These three genes are candidates for an EAC signature and further evaluations of their involvement in EAC tumorigenesis will be undertaken.
Highlights
In the Western world, endometrial cancers are the most common gynaecological neoplastic disorders among women
Endometrial carcinomas (ECs) can be divided into two broad categories based on morphology; Type I endometrial cancer, which accounts for approximately 70–80% of all ECs, follows the estrogen-related pathway and frequently develops in the setting of complex atypical hyperplasias as malignant precursors
Gene function classification Out of the top 50 genes, 31 genes were found to be involved in cellular processes commonly implicated in human tumorigenesis (Figure 2a)
Summary
In the Western world, endometrial cancers are the most common gynaecological neoplastic disorders among women. Endometrial carcinomas (ECs) are the most frequently occurring malignancies in the genital tract among women in the Western world. As in most other cancer diseases, neoplastic progression to EC is very complex, and involves high penetrance genes as well as intricate interactions of multiple low penetrance genes [1]. ECs can be divided into two broad categories based on morphology; Type I endometrial cancer, which accounts for approximately 70–80% of all ECs, follows the estrogen-related pathway and frequently develops in the setting of complex atypical hyperplasias as malignant precursors. Endometrial adenocarcinoma (EAC) is the most common type I EC and originates from the glandular cells of the uterus surface epithelium. Type I tumors occur pre-dominantly in pre- or peri-menopausal women, whereas the more aggressive type II tumors occur in post-menopausal (page number not for citation purposes)
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