Cancer-Associated Mutations in Endometriosis without Cancer
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PROVIDER: EGAS00001003576 | EGA |
REPOSITORIES: EGA
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Project description:Endometriosis is a common disease seen by gynecologists. Clinical features involve pelvic pain and unexplained infertility. Although endometriosis is pathologically characterized by endometrial tissue outside the normal uterine location, endometriosis is otherwise not easily explained. Endometriomas, endometriotic cysts of the ovary, typically cause pain and distortion of pelvic anatomy. To begin to understand the pathogenesis of endometriomas, we carried out transcriptome:microRNAome analysis of endometriomas and eutopic endometrium, using gene expression arrays and next generation small RNA sequencing technology. Keywords: two group comparison Patients undergoing surgery for endometriomas, suspected endometriosis, pelvic pain, abnormal uterine bleeding, pelvic organ prolapse, or uterine leiomyomas were approached for participation. After informed consent, the patients underwent scheduled surgical procedure. Tissues were collected either as cyst wall of endometrioma or endometrial curettage of hysterectomy specimen and placed directly into RNALater (Ambion, Austin, TX) and eventually frozen at -80?C. Samples were designated as endometriomas or non-endometriosis control endometrium based on surgical pathology reports. Total RNA was isolated from frozen tissue. High quality RNA was subjected to Illumina’s Human WG-6 version 2.0 BeadChips (Illumina). . *** This Series represents the transcriptome component of the study. ***
2011-05-09 | E-GEOD-23339 | biostudies-arrayexpress
Project description:Endometriosis is a common disease seen by gynecologists. Clinical features involve pelvic pain and unexplained infertility. Although endometriosis is pathologically characterized by endometrial tissue outside the normal uterine location, endometriosis is otherwise not easily explained. Endometriomas, endometriotic cysts of the ovary, typically cause pain and distortion of pelvic anatomy. To begin to understand the pathogenesis of endometriomas, we carried out transcriptome:microRNAome analysis of endometriomas and eutopic endometrium, using gene expression arrays and next generation small RNA sequencing technology. Keywords: two group comparison
2011-05-09 | GSE23339 | GEO
Project description:Endometriosis is characterized by growth of endometrial-like tissue outside of the uterus affecting many women during their reproductive age, causing years of pelvic pain and potential infertility. Its pathophysiology remains largely unknown, limiting early diagnosis and treatment. We characterized peritoneal and ovarian lesions at single-cell transcriptome resolution and compared to matched eutopic endometrium, control endometrium, and organoids derived from these tissues, generating data on over 122,000 cells across 14 individuals. We spatially localized many of the cell types using imaging mass cytometry. We identify a perivascular mural cell unique to the peritoneal lesions with dual roles in angiogenesis promotion and immune cell trafficking. We define an immunotolerant peritoneal niche, fundamental differences in eutopic endometrium and between lesions microenvironments, and an unreported progenitor-like epithelial cell subpopulation. Altogether, this study provides a holistic view of the endometriosis microenvironment representing a comprehensive cell atlas of the disease in hormonally treated patients, essential information for advancing therapeutics and diagnostics.
2022-05-05 | GSE179640 | GEO
Project description:Endometriosis is a common, chronic inflammatory condition that frequently results in pain and infertility and is estimated to affect 6–10% of women of reproductive age. However, the mechanisms underlying the induction of inflammation in endometriosis remain unclear. Here, we identified that ectopic endometrial T-cell-derived active interleukin (IL)-16 acts as an inflammation-driving cytokine in endometriosis. Furthermore, we found that in ectopic endometrial T cells, the activation of IL-16 requires iron overload-induced caspase-3 activity and that the release of active IL-16 is reliant on GSDME-mediated pyroptosis. These observations suggest that active IL-16 may represent a promising target in the treatment of endometriosis.
2024-04-10 | GSE229735 | GEO
Project description:Endometriosis is a common gynecological disorder characterized by pain and infertility, where the lesions disseminate everywhere in the body with a preference for the pelvis. In that, it could be regarded as a âbenign metastatic diseaseâ, since its issue is not fatal. However, the molecular bases of this intriguing clinical condition are not well known. The objective of this study is to characterize the transcriptome differences between eutopic vs ectopic endometrium with a special interest in pathways involved in cancerogenesis. We performed two hybridizations in technical replicate on highly specific long oligonucleotides microarrays (NimbleGenâ¢), with cDNA prepared from 6-patients pools, where the same patient provided both eutopic and ectopic endometrium (endometriomas). In order to confirm the expression microarrays data, qRT-PCR validation was performed on 12 individuals for 20 genes. Over 8,000 transcripts were significantly modified (more than twice) in the lesions corresponding to 5,600 down- or up-regulated genes. These were clustered through DAVID Bioinformatics Resources into 55 functional groups. The data are presented in a detailed and visual way on 24 KEGG pathways implemented with induction ratios for each differentially expressed gene. An outstanding control of the cell cycle and a very specific modulation of the HOX genes were observed and provide some new evidence on why endometriosis only very rarely degenerates into cancer. The study constitutes a noteworthy update of gene profiling in endometriosis, by delivering the most complete and reliable list of dysregulated genes to date. Keywords: Gene expression microarrays We performed two hybridizations in technical replicate on highly specific long oligonucleotides microarrays (NimbleGenâ¢), with cDNA prepared from 6-patients pools, where the same patient provided both eutopic and ectopic endometrium (endometriomas)
2010-06-19 | E-GEOD-12768 | biostudies-arrayexpress
Project description:Mechanisms of immune dysregulation against established tumors are relatively well understood. Much less is known about the role of immune effectors against cancer precursor lesions. Endometrioid and clear cell ovarian tumors may partly derive from endometriosis, a commonly diagnosed chronic inflammatory disease. We performed here the most comprehensive immune gene expression analysis of pelvic inflammation in endometriosis and endometriosis-associated ovarian cancer (EAOC).
2015-01-07 | GSE57545 | GEO
Project description:Endometriosis is a benign gynecological condition that causes significant morbidity due to reduced fertility, pelvic pain and inflammatory dysfunctions. High-fat dietary intake has been linked to higher systemic inflammation and oxidative stress, which are both features of women with endometriosis. We evaluated the effects of high-fat diet (HFD) on endometriosis progression using immunocompetent mouse model wherein ectopic lesion was induced in wildtype and kruppel-like factor 9 (KLF9)- null donor mice. Results showed that HFD leads to increased ectopic lesion numbers and higher body weight gain. The HFD-promotion of lesion establishment was associated with decreased stromal estrogen receptor 1 and progesterone receptor expression, increased macrophage infiltration, and enhanced expression of pro-inflammarory and pro-oxidative stress pathway genes. Further, lesion-bearing mice had higher peritoneal fluid TNF-α and elevated local/systemic redox status than control-fed mice.
2017-04-23 | GSE80603 | GEO
Project description:Endometriosis, an estrogen-dependent, progesterone-resistant, inflammatory disorder affects 10% of reproductive-age women. It is diagnosed and staged at surgery, resulting in an 11-year latency from symptom onset to diagnosis, underscoring the need for less invasive, less expensive approaches. Since the uterine lining (endometrium) in women with endometriosis has altered molecular profiles, we tested whether molecular classification of this tissue can distinguish and stage disease. We developed classifiers using genomic data from n=148 archived endometrial samples from women with endometriosis or without endometriosis (normal controls or with other common uterine/pelvic pathologies) across the menstrual cycle and evaluated their performance on independent sample sets. Classifiers were trained separately on samples in specific hormonal milieu, using margin tree classification, and accuracies were scored on independent validation samples. Classification of samples from women with endometriosis or no endometriosis involved two binary decisions each based on expression of specific genes. These first distinguished presence or absence of uterine/pelvic pathology and then no endometriosis from endometriosis, with the latter further classified according to severity (minimal/mild or moderate/severe). Best performing classifiers identified endometriosis with 90-100% accuracy, were cycle phase-specific or independent, and utilized relatively few genes to determine disease and severity. Differential gene expression and pathway analyses revealed immune activation, altered steroid and thyroid hormone signaling/metabolism and growth factor signaling in endometrium of women with endometriosis. Similar findings were observed with other disorders versus controls. Thus, classifier analysis of genomic data from endometrium can detect and stage pelvic endometriosis with high accuracy, dependent or independent of hormonal milieu. We propose that limited classifier candidate-genes are of high value in developing diagnostics and identifying therapeutic targets. Discovery of endometrial molecular differences in the presence of endometriosis and other uterine/pelvic pathologies raises the broader biological question of their impact on the steroid hormone response and normal functions of this tissue. We analyzed endometrial samples from n=148 women without or with endometriosis and/or other uterine/pelvic pathologies, using whole genome microarrays.
2014-10-01 | E-GEOD-51981 | biostudies-arrayexpress
Project description:Endometriosis is a complex pathological condition in which multiple components are involved in the disease development and clinical outcome. Endometriosis is mainly an inflammatory codition estrogen-dependent, with unknown pathogenesis, that is characterized by dissemination of edometrium tissue in ectopic position (ovary or pelvic peritoneum). Two main theories rise the pathologic onset: the presence of retrograde menstruation and celomic metaplasia in the pelvic peritoneum, that can occur for development defects. Endometriosis is related not only to genetic or immunological changes and to environmental pollution factors, as the endocrine interferents. The disease phenotype results from multiple events (genetics and enviromental), thus it is difficult to find a single gene as causative while is more probable that a gene network/s might involved in the onset and mantainement of the disease state. The peculiarity of endometriosis rely on the tissue speificity manteinance in the ectopic position, where it responds to the hormone stimuli as the tissue in the eutopic position. In order to identify genes potentially involved in growth and mainteinance of the ectopic endometrium, we have profiled ectopic (8 samples) and eutopic endometrium (8 samples) from several affected woman in the proliferative phase. As control we used endometrium from normal health donors in the same phase (6 samples).
2013-11-30 | E-GEOD-25628 | biostudies-arrayexpress
Project description:Endometriosis is a chronic, estrogen-dependent gynecological condition that affects approximately 10% of women of reproductive age. The most widely accepted theory of the etiology of endometriosis includes the process of retrograde menstruation, where menstrual effluent travels up the Fallopian tubes, accesses the peritoneal cavity, and in some people is able to establish endometriotic lesions. Recent reports suggest the uterus is not devoid of bacteria, as was once believed. Thus, the refluxed menstrual effluent may also carry bacteria along with it, and this bacteria has been suggested to contribute to inflammation, and establishment and growth of endometriotic lesions. Here, we sought to compare and contrast the uterine bacteria (endometrial microbiota) in women with surgically confirmed presence or absence of endometriosis using next-generation 16S rRNA gene sequencing. We obtained an average of more than 9000 sequence reads per endometrial biopsy, and found that the endometrial microbiota of women with endometriosis was more diverse (greater Shannon Diversity Index and greater proportion of ‘Other’ taxa) than that of symptomatic controls (women with pelvic pain, but with surgically confirmed absence of endometriosis; diagnosed with other benign gynecological conditions at surgery). The difference in endometrial microbiotas was supported in unsupervised cluster analyses where some clustering of endometrial microbiota by disease status (endometriosis vs. controls) was observed. The bacterial taxa enriched in the endometrial microbiota of women with endometriosis belonged to the Actinobacteria phylum, Oxalobacteraceae and Streptococcaceae families, and Tepidimonas genus, while those enriched in the symptomatic controls (without endometriosis) belonged to the Burkholderiaceae family, and Ralstonia genus. Taken together, our findings suggest the endometrial microbiota is perturbed in people with endometriosis.
2021-04-16 | GSE172172 | GEO