Cell state dynamics during early stages of serous endometrial carcinoma
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PROVIDER: PRJNA1121235 | ENA |
REPOSITORIES: ENA
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Project description:Serous endometrial carcinoma (SEC) is one of the most aggressive and lethal types of uterine cancer, responsible for about 40% of all endometrial cancer-related deaths. Due to the rapid progression of SEC, early detection of this disease is of utmost importance. However, molecular and cellular dynamics during the pre-dysplastic stage of this disease remain largely unknown. Here, we provide a comprehensive census of cell types and their states for normal, pre-dysplastic, and dysplastic endometrium in a mouse model of SEC. This model is associated with inactivation of tumor suppressor genes Trp53 and Rb1, whose pathways are altered frequently in SEC. We report that pre-dysplastic changes are characterized by expanded and increasingly diverse immature luminal epithelial cell populations. Decrease of differentiated cell states is accompanied by a previously unreported reduction in number and strength of predicted interactions between epithelial and stromal endometrial cells. Such reduction is transient and is followed by formation of a new set of intercellular interactions marking further cancer progression. By using a multi-level approach combining single-cell and spatial transcriptomics paired with screening for clinically relevant genes in human endometrial carcinoma, we identified a panel of genes with potential use as early diagnostic, prognostic, and therapeutic targets. In summary, our results suggest an important role of luminal epithelial cell state in SEC pathogenesis, uncover transient reduction in cell-cell interactions prior the onset of cancer-associated dysplastic changes, and validate our mouse SEC model as a promising comparative platform in preclinical settings.
2025-08-08 | GSE269332 | GEO
Project description:GATA2 expression in endometrial serous carcinoma cells correlates with patient outcome. Depletion of GATA2 in patient-derived endometrial serous carcinoma cell lines correlates with invasive potential. As GATA2 is a transcription factor, we hypothesize that GATA2-dependent target genes normally suppress invasion in endometrial serous carcinoma.
2025-03-06 | GSE264610 | GEO
Project description:In order to classify the endometrium and serous of endometrial cancer, we try to find genes expressed differently between the two groups.
2025-05-28 | GSE271199 | GEO
Project description:In order to classify the endometrium and serous of endometrial cancer, we try to find genes expressed differently between the two groups.
2025-05-28 | GSE271198 | GEO
Project description:Effect of GATA2 depletion on Ark1 endometrial serous carcinoma cells.
| PRJNA1103234 | ENA
Project description:To determine the expression profiles of microRNAs (miRNAs) and to examine specific miRNA expression in endometrial serous adenocarcinoma in comparison with normal endometrial tissue and endometrial endometrioid adenocarcinoma. Twenty-one serous adenocarcinoma tissues, 20 endometrioid adenocarcinoma tissues, and 7 normal endometrial tissues were enrolled. miRNA expression profiles were examined using miRNA microarray.
2018-11-01 | GSE25405 | GEO
Project description:Endometrial cancer (EC) is the most common female genital malignancy and the fourth most common cancer in women in the developing world1. EC has been traditionally classified into two main groups with different clinical, pathological and molecular features2,3. Type I or endometrioid endometrial carcinomas (EECs) account for about 75% of the cases and are typically estrogen-related and low-grade tumors with good prognosis that coexist or are preceded by endometrial hyperplasia, mainly diagnosed in perimenopausal women. In contrast, type II or non-endometrioid endometrial carcinomas (NEECs) are high-grade aggressive tumors associated with endometrial atrophy and poor prognosis, unrelated to estrogen and diagnosed in older women. These comprise several histological subtypes, being the most common the serous carcinomas (SEC)4. In recent years numerous large-scale studies of primary endometrioid and serous tumors have been performed5, revealing new mutated genes and establishing a new molecular subclassification based on the results obtained by The Cancer Genome Atlas (TCGA) consortium6, which implies different clinical outcomes. More recently, the genomic evolution of EC has been analyzed through a comparative study of samples from endometrial atypical hyperplasia, primary tumors and paired metastases7, revealing the presence of intratumor heterogeneity as previously described in primary EC and other tumor types8,9. However an in-depth study considering multiple regions from primary tumor and paired metastases has not been performed up to now to our knowledge. Here we analyze by whole-exome sequencing (WES), massive parallel targeted sequencing and array comparative genomic hybridization (aCGH) the clonal evolution and intratumor heterogeneity of 7 endometrioid and 3 serous metastatic endometrial carcinomas. Different locations from the primary tumor as well as from their paired metastases were included in the study, allowing the reconstruction of the spatial and temporal phylogenetic evolution of the tumor. Different phylogenetic evolution patterns were identified, independently of the classical histological or molecular classification of the tumor, although similar patterns were found in ovarian metastasis and recurrent disease.
2022-02-14 | GSE101447 | GEO
Project description:Classically, there are two types of endometrial cancer, endometrioid adenocarcinoma (EAC), or Type I; and uterine papillary serous carcinoma (UPSC), or Type II. These two types of cancers exhibit distinct DNA methylation levels in promoters of many genes. In EAC, many tumor suppressor genes were silenced due to DNA hypermethylation at their promoter region. However, promoters of many of these genes remained unmethylated in UPSC. Here, we described complete DNA methylome maps of endometrioid adenocarcinoma, uterine papillary serous carcinoma, and normal endometrium, by applying a combined strategy of methylated DNA immunoprecipitation sequencing (MeDIP-seq) and methylation-sensitive restriction enzyme sequencing (MRE-seq). We took a complementary and orthogonal approach to identify DNA methylation changes unique to the two endometrial cancer subtypes in an unbiased fashion. We generated complete DNA methylome maps for endometrioid adenocarcinoma (EAC, three samples), uterine papillary serous carcinomas (UPSC, three samples), and normal endometrium (pooled samples) by integrating data from methylated DNA immunoprecipitation sequencing (MeDIP-seq) and methylation-sensitive restriction enzyme sequencing (MRE-seq).
2014-10-12 | E-GEOD-51565 | biostudies-arrayexpress
Project description:Endometrial cancer is one of the most common gynecologic malignancies, and patients with high grade disease, especially serous papillary subtype (SPEC) are often related to the poor outcomes. Recent genome-wide analyses have revealed that SPEC exhibits gene expression profiles that are distinct from the endometrioid histologic subtype; therefore, it is important to identify the SPEC driver genes or pathways responsible for the inherently aggressive phenotypes and to develop SPEC-specific therapies to target these driver genes or pathways. Through array-based analysis and immunohistochemical staining of human endometrial cancer tissue, STAT1 is identified high expressed, and can distinguish SPEC from other subtypes of endometrial cancer. In vitro and in vivo experiments show STAT1 role as a pro-survival factor in SPEC. STAT1 was identified as a master gene modulating “transcriptional pro-survival pathways” to enhance multiple malignant characteristics These finding may suggest that targeting of STAT1, the SPEC driver gene, may provide the means to improve poor outcomes for patients with SPEC. We used microarrays to clarify the changes of gene expression along with STAT1-siRNA treatment and to confirm whether there are any changes on genes expression related to STAT1 pathway. We also used the microarray data to clarify genes signatures which can distinguish subtype of human endometrial cancers.
2014-03-20 | E-GEOD-56026 | biostudies-arrayexpress
Project description:Objectives: The aim of this study was to identify the dysregulated genes involved in tumorigenesis, invasion, and metastasis of endometrial endometrioid adenocarcinoma (EEC). Materials and methods: Surgical specimens of endometrial tissues were obtained from 20 patients with normal endometrium (NEM), 20 patients with atypical endometrial hyperplasia (AEH), and 169 patients with EEC. The expression profiles of NEM, AEH, and EEC were compared by using GeneChip Array. The expression of dysregulated genes was first validated by semi-quantitative reverse transcriptase PCR (SQ RT-PCR). The gene expression levels were determined by real time reverse transcriptase PCR (RTQ RT-PCR) in 85 EEC patients as the training test and 84 EEC patients as the testing test. The protein expressions were then examined by immunohistochemical (IHC) staining. The correlations between the expression of dysregualted genes and clinico-pathologic parameters such as tumorigenesis, invasion, and metastasis of EEC were finally evaluated. Results: Seven dysregulated genes were identified by SQ RT-PCR after microarray analysis. Conclusions: uPA is a dysregulated gene in the tumorigenesis of endometrial carcinomas. The gene expression between tissues from NEM, AEH, and EEC were analyzed by microarray. The samples were grouped according to clinical stages but selected at random from our list of banked, frozen tissues. Ten NEM, 10 AEH, and 20 EEC of early and advanced stages were used for microarray experiments (Group 1: early-staged (stages I and II) EEC (n=10), Group 2: advanced-staged EEC (stages III and IV) (n=10)). Samples were pooled in equimolar amounts (10 samples / pool) for microarray analysis.
2016-01-18 | E-GEOD-39099 | biostudies-arrayexpress