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Transcriptome and DNA methylation analyses highlight the role of menstrual cycle phase in tumorigenesis of endometriosis-related ovarian carcinoma histotypes [RNA-Seq]

ABSTRACT: Transcriptome and DNA methylation analyses highlight the role of menstrual cycle phase in tumorigenesis of endometriosis-related ovarian carcinoma histotypes [RNA-Seq]

PROVIDER: PRJNA941916 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR23729700_1.fastq.gz	Fastqsanger.gz
	SRR23729700_2.fastq.gz	Fastqsanger.gz
	SRR23729701_1.fastq.gz	Fastqsanger.gz
	SRR23729701_2.fastq.gz	Fastqsanger.gz
	SRR23729702_1.fastq.gz	Fastqsanger.gz

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Transcriptome and DNA methylation analyses highlight the role of menstrual cycle phase in tumorigenesis of endometriosis-related ovarian carcinoma histotypes.

Project description:Transcriptome and DNA methylation analyses highlight the role of menstrual cycle phase in tumorigenesis of endometriosis-related ovarian carcinoma histotypes.

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Transcriptome and DNA methylation analyses highlight the role of menstrual cycle phase in tumorigenesis of endometriosis-related ovarian carcinoma histotypes [methylation]

Project description:Transcriptome and DNA methylation analyses highlight the role of menstrual cycle phase in tumorigenesis of endometriosis-related ovarian carcinoma histotypes [methylation]

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Transcriptome and DNA methylation analyses highlight the role of menstrual cycle phase in tumorigenesis of endometriosis-related ovarian carcinoma histotypes [methylation]

Project description:Epithelial ovarian cancer, or ovarian carcinoma (OC), is a diverse disease. Two of the rarer subtypes, clear cell OC (CCOC) and endometrioid OC (ENOC), both arise from ovarian endometriotic cysts, particularly atypical endometriosis. CCOC and ENOC have similar mutation profiles and share a common cell of origin, but their cellular phenotypes and clinical outcomes are distinct; in particular, CCOC has poor clinical survival. The most well-known difference between the histotypes is the universal overexpression of HNF1B (Hepatocyte nuclear factor-1β) in clear cell tumors and overexpression of ESR1 in ENOC. It is not well understood how these discrete histotypes arise from the same cell of origin. Via transcriptional (n=57) and DNA methylation analysis (N=127) of these rare tumors, we show that CCOC closely resembles secretory endometrium in transcriptional profile; whereas ENOC transcriptomes resemble proliferative endometrium.

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Transcriptome and DNA methylation analyses highlight the role of menstrual cycle phase in tumorigenesis of endometriosis-related ovarian carcinoma histotypes [RNA-Seq]

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Project description:Endometriosis is associated with increased risk of epithelial ovarian cancers (EOCs). Using data from large endometriosis and EOC genome-wide association meta-analyses we estimate the genetic correlation and evaluate the causal relationship between genetic liability to endometriosis and EOC histotypes, and identify shared susceptibility loci. We estimate a significant genetic correlation (rg) between endometriosis and clear cell (rg=0.71), endometrioid (rg=0.48) and high-grade serous (rg=0.19) ovarian cancer, associations supported by Mendelian randomization analyses. Bivariate meta-analysis identify 28 loci associated with both endometriosis and EOC, including 19 with evidence for a shared underlying association signal. Differences in the shared risk suggest different underlying pathways may contribute to the relationship between endometriosis and the different histotypes. Functional annotation using transcriptomic and epigenomic profiles of relevant tissues/cells highlights several target genes. This comprehensive analysis reveals profound genetic overlap between endometriosis and EOC histotypes with valuable genomic targets for understanding the biological mechanisms linking the diseases.

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Project description:Given the importance of menstrual blood in the pathogenesis of endometriosis and the multifunctional roles of menstrual mesenchymal stem cells (MenSCs) in regenerative medicine, this issue has gained prominence in the scientific community. Moreover, recent reviews highlight how robust the integrated assessment of omics data is for endometriosis. To our knowledge, no study has applied the multi-omics approaches to endometriosis MenSCs. It is a case-control study at a university-affiliated hospital. MenSCs transcriptome and proteome data were obtained by RNA-seq and UHPLC- MS/MS detection. Among the differentially expressed proteins and genes, we emphasize ATF3, ID1, ID3, FOSB, SNAI1, NR4A1, EGR1, LAMC3, and ZFP36 genes and MT2A, TYMP, COL1A1, COL6A2, and NID2 proteins that were already reported in the endometriosis. Our functional enrichment analysis reveals integrated modulating signaling pathways such as epithelial-mesenchymal transition (↑) and PI3K signaling via AKT to mTORC1 (↓in proteome), mTORC1 signaling, TGF beta signaling, TNFA signaling via NFkB, and response to hypoxia via HIF1A targets (↑in transcriptome). Our findings highlight primary changes in the endometriosis MenSCs, suggesting that the chronic inflammatory endometrial microenvironment can modulate these cells, providing opportunities for endometriosis etiopathogenesis. Moreover, they identify challenges for future research leveraging knowledge for regenerative and precision medicine in endometriosis.

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Project description:This project aims at comparing endometrium from women with and without endometriosis during the secretory phase of menstrual cycle. The present results constitute a first step towards identifying potential diagnosis biomarkers and may provide a better understanding of endometriosis especially the etiology of the disease.

2022-04-01 | PXD012981 | Pride