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The role of EP-2 receptor expression in cervical intraepithelial neoplasia.

ABSTRACT: Prostaglandin induced signalling is involved in different cancers. As previously described, the EP3 receptor expression decreases with increasing stage of cervical intraepithelial lesions (CIN). In addition, in cervical cancer EP3 is an independent prognosticator for overall survival and correlates with FIGO stages. Currently the role of Prostaglandin 2 receptor 2 (EP2) in CIN is unknown. The aim of this study was to analyse the expression of EP2 for potential prognostic value for patients with cervical dysplasia. EP2 expression was analysed by immunohistochemistry in 33 patient samples (CIN1-3) using the immune-reactivity scoring system (IRS). Expression levels were correlated with clinical outcome to analyse prognostic relevance in patients with CIN2. Data analysis was performed using non parametric Kruskal-Wallis and Spearman rank sum test. Cytoplasmic expression levels of EP2 correlated significantly (p?

SUBMITTER: Schmoeckel E

PROVIDER: S-EPMC7723936 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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The role of EP-2 receptor expression in cervical intraepithelial neoplasia.

Schmoeckel Elisa E Fraungruber Patricia P Kuhn Christina C Jeschke Udo U Mahner Sven S Kolben Theresa Maria TM Kolben Thomas T Vilsmaier Theresa T Hester Anna A Heidegger Helene Hildegard HH

Histochemistry and cell biology 20200826 6

Prostaglandin induced signalling is involved in different cancers. As previously described, the EP3 receptor expression decreases with increasing stage of cervical intraepithelial lesions (CIN). In addition, in cervical cancer EP3 is an independent prognosticator for overall survival and correlates with FIGO stages. Currently the role of Prostaglandin 2 receptor 2 (EP2) in CIN is unknown. The aim of this study was to analyse the expression of EP2 for potential prognostic value for patients with ...[more]

PMID: 32851536

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Project description:The highest rates of cervical cancer are found in developing countries. Frontline monitoring has reduced these rates in developed countries and present day screening programs primarily identify precancerous lesions termed cervical intraepithelial neoplasias (CIN). CIN lesions described as mild dysplasia (CIN I) are likely to spontaneously regress while CIN III lesions (severe dysplasia) are likely to progress if untreated. Thoughtful consideration of gene expression changes paralleling the progressive pre invasive neoplastic development will yield insight into the key casual events involved in cervical cancer development.In this study, we have identified gene expression changes across 16 cervical cases (CIN I, CIN II, CIN III and normal cervical epithelium) using the unbiased long serial analysis of gene expression (L-SAGE) method. The 16 L-SAGE libraries were sequenced to the level of 2,481,387 tags, creating the largest SAGE data collection for cervical tissue worldwide. We have identified 222 genes differentially expressed between normal cervical tissue and CIN III. Many of these genes influence biological functions characteristic of cancer, such as cell death, cell growth/proliferation and cellular movement. Evaluation of these genes through network interactions identified multiple candidates that influence regulation of cellular transcription through chromatin remodelling (SMARCC1, NCOR1, MRFAP1 and MORF4L2). Further, these expression events are focused at the critical junction in disease development of moderate dysplasia (CIN II) indicating a role for chromatin remodelling as part of cervical cancer development.We have created a valuable publically available resource for the study of gene expression in precancerous cervical lesions. Our results indicate deregulation of the chromatin remodelling complex components and its influencing factors occur in the development of CIN lesions. The increase in SWI/SNF stabilizing molecule SMARCC1 and other novel genes has not been previously illustrated as events in the early stages of dysplasia development and thus not only provides novel candidate markers for screening but a biological function for targeting treatment.

Project description:The aim of the present study was to identify the differentially expressed genes between cervical intraepithelial neoplasias (CIN) and adjacent normal tissue, and to construct a protein-protein interaction (PPI) network. A CIN dataset was obtained from Gene Expression Omnibus, and data of gene expression in CIN and adjacent normal tissue were extracted from GSE64217. The differentially expressed genes were selected using software package and heat map was drawn using the 'pheatmap' package. The selected differentially expressed genes were subjected to PPI, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis using Cytoscape, Database for Annotation, Visualization and Integrated Discovery, STRING and KOBAS. In the present study, 287 genes were differentially expressed between CIN and adjacent normal tissue, of which 170 were significantly upregulated and 118 genes were significantly downregulated (P<0.00001, fold-change >6). A differential gene expression network map was constructed to show the interactions of 30 protein products encoded by differentially expressed genes using STRING software. In particular, the key gene, EGR1, was identified using Cytoscape software. The KEGG pathway analysis revealed that the differential genes were mainly involved in several pathways, including 'glutathione metabolism', 'arachidonic acid metabolism', and 'pentose phosphate pathway'. Results of the GO analysis showed that differential genes were enriched in different subsets. Specifically, small proline-rich protein 2E and 3, distal-less homeobox 5, epithelial membrane protein 1, cornifelin, periplakin, homeobox protein Hox-A13, estrogen receptor α, transglutaminase 1, small proline-rich protein 2A, Rh C glycoprotein, tumor protein p63, TGM3, homeobox B5 and small proline-rich protein 2D were enriched in 'epithelial cell differentiation', which affected the differentiation of epithelial cells. In conclusion, 287 differentially expressed genes were identified successfully. The key gene was identified based on the results of PPI, GO and KEGG analyses, and functional annotation and pathway analysis were also performed. Our study provides the basis for further studies on the interaction among differentially expressed genes.

Dataset Information

The role of EP-2 receptor expression in cervical intraepithelial neoplasia.

Publications

The role of EP-2 receptor expression in cervical intraepithelial neoplasia.

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