5904276c-fbb3-488c-870d-b06a6864096e - samples
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ABSTRACT:
PROVIDER: EGAD00001011123 | EGA |
REPOSITORIES: EGA
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Project description:Purpose: Current diagnostic methods for endometrial cancer lack specificity, leading to many women undergoing invasive procedures. The aim of this study was to evaluate somatic mutations in urine to accurately discriminate endometrial cancer patients from controls.
Experimental Design: Overall, 72 samples were analyzed using next-generation sequencing with molecular identifiers targeting 47 genes. We evaluated urine supernatant samples from women with endometrial cancer (n=19) and age-matched controls (n=20). Cell pellets from urine and plasma samples from seven cases were sequenced; further, we also evaluated paired tumor samples from all cases. Finally, immunohistochemical markers for molecular profiling were evaluated in all tumor samples.
Results: Overall, we were able to identify mutations in DNA from urine supernatant samples in 100% of endometrial cancers. In contrast, only one control (5%) showed variants at a variant allele frequency (VAF)≥2% in the urine supernatant samples. The molecular classification obtained by using tumor samples and urine samples showed good agreement. Analyses in paired samples revealed a higher number of mutations and VAFs in urine supernatants than in urine cell pellets and blood samples.
Conclusions: Evaluation of somatic mutations using urine samples may offer a user-friendly and reliable tool for endometrial cancer detection and molecular classification. The diagnostic performance for endometrial cancer detection was very high, and cases could be molecularly classified using these noninvasive and self-collected samples. Additional multi-center evaluations using larger sample sizes are needed to validate the results and understand the potential of urine samples for the early detection and prognosis of endometrial cancer.
| EGAS00001007396 | EGA
Project description:Biological implications of healthy- and tumor-specific ERα cistromes in endometrial tumors have largely been understudied. Moreover, the functional impact of non-coding somatic variants has commonly been underexplored and remained elusive. This study is aimed to provide functional interpretation of non-coding somatic variants associated with tumor-specific ERα cistrome. Integrating the ChIP-seq analyses with the whole genome sequencing from the set of metastatic endometrial tumors and matched controls we observed that tumor-specific ERα cistrome is enriched for somatic variants. Additionally, H3K27Ac Hi-ChIP in cancer cell lines identified potential target genes of tumor-specific enhancers and coincident variants. We aim to employ CRISPR to identify tumor-specific ERα enhancers and target genes critical for estrogen-driven proliferation of endometrial cancer-cell lines. Through multidimensional omics data integration, our study is specifically geared to shed new lights on the molecular mechanisms of endometrial cancer development and progression and the functional impact of non-coding somatic mutations.
2025-04-15 | PXD029822 | Pride
Project description:Improving embryo implantation rates has become one of the greatest challenges in assisted reproduction techniques. Implantation process requires a synchrony between the development of the embryo and the endometrium, but also, an adequate embryo-endometrial crosstalk. MicroRNAs (miRNAs) and extracellular vesicles (EVs) from endometrial fluid (EF) have been described to be mediators of this communication. Therefore, the molecular analysis of the miRNA content of EF could provide a non-invasive method to recognize an implantative endometrium and consequently improve the implantation rates. In this work, we optimized EF sample collection procedure and performed a comparative analysis of five different methodologies to enrich miRNA content of EF with the purpose of identifying a simple, sensitive, reproducible and non-invasive method that allow the quick identification of an implantative endometrium. Then, we applied the selected methodology in a set of real samples with different implantation outcome. Our results showed that EVs enrichment protocols permit to detect a higher number of miRNAs. In addition, we obtained two predictive models based on three miRNAs that allow us to differentiate between an implantative and non-implantative endometrium. Model 1 (Area under the curve (AUC)=0.93; p-value=0.0033): hsa-miR-200b-3p, hsa-miR-24-3p and hsa-miR-148b-3p. Model 2 (AUC=0.92; p-value=0.0002): hsa-miR-200b-3p, hsa-miR-24-3p and hsa-miR-99b-5p. This work supports the feasibility to analyze EVs and EVs-associated miRNAs from a small volume of EF sample and the development of EV-miRNAs based assays as low-invasive tools for the detection of an implantative endometrium.
2022-08-18 | GSE178917 | GEO
Project description:Objective: To evaluate if the inflammatory proteomics of uterine fluid could define the endometrial receptivity phase. Methods: Inflammatory proteomics of uterine fluid were measured using the OLINK Target-96 Inflammation panel. Endometrial receptivity testing (ERT) combined with endometrial dating was a gold standard for defining the endometrial receptivity phase. A predictive model based on proteomics of uterine fluid was established to predict the endometrial receptivity phase. Results: The inflammatory factors in uterine fluid were differentially expressed between window of implantation (WOI) and displaced WOI groups, and the displaced WOI group was characterized by the increased expression of a variety of inflammatory factors. The predictive model established based on the top 5 differential proteins could accurately classify the endometrial receptive phase. Transcriptomic data from endometrial tissues showed that the differential gene sets between different receptive phases were mostly enriched in immune-related processes, and the expression of immune-related genes in the WOI group was significantly lower than that in the displaced WOI group. Conclusions: Detection of inflammatory proteins from the uterine fluid using the OLINK inflammation panel could be a novel non-invasive method to define the endometrial receptive phase. The inflammatory immune response during the embryo implantation window was inhibited to adapt to the implantation of the semi-alloimmune embryos.
2025-12-31 | GSE283724 | GEO
Project description:Current endometrial receptivity tests require an invasive method of collecting of endometrial biopsies that can cause general discomfort and adverse events such as infections, pain, and bleeding. Therefore, minimally-invasive methodologies for receptivity evaluation are needed. Cervical cells could offer a great potential for endometrial receptivity testing because cervical cell collection by cytobrush is a standardized, quick, simple, well tolerated, minimally invasive and routinely used sampling technique in everyday gynaecological practice. To date, no studies have evaluated the suitability of cervical cells for endometrial receptivity testing based on transcriptional profiling throughout the menstrual cycle. In this study, paired samples of the endometrium and cervical cells were obtained from 20 women in different menstrual cycle time-points in natural cycles and women undergoing hormonal replacement cycles. The gene expression profiles of cervical cells showed no apparent clustering according to their collection time and menstrual cycle phase. Transcriptome analysis identified only four (KIF2C, CENPF, HLA-DRB5 and CUTALP) differentially expressed genes between the early- and mid-secretory samples, suggesting that the transcriptomes of cervical cells, in contrast to endometrial tissue, do not exhibit significant differences during the window of implantation opening. The largest differences in the transcriptome of cervical cells were noticed in late-secretory phase, before initiation of menstruation. The results of our study suggested that cervical cells’ transcriptome does not reflect the gene expression pattern of endometrial tissue during the WOI and these cells offer little or no potential for endometrial receptivity diagnostics.
2023-07-09 | GSE221127 | GEO
Project description:Background: Since 2016, a project for molecular diagnosis of childhood medulloblastoma (MB) was initiated in Taiwan. We aimed to integrate molecular classification, molecular and clinical risk factors, somatic mutations, and phenotypic traits for up to date adaptive care. Method: Fifty-two MBs in children with frozen tumor tissue were assembled. Clinical data were retrieved. RNA-Seq and DNA methylation array data were generated. Molecular subgrouping and molecular-clinical correlation were performed. Subgroup-based risk stratification included an adjusted Heidelberg risk stratification scheme were defined and evaluated. We selected 51 genes for somatic variant calling using RNA-Seq. Relevant phenotypic traits were defined for the linkage of genetic predisposition. Results: Four core molecular subgroups (WNT, SHH, Group 3, and Group 4) were identified. Genetic backgrounds of metastasis at diagnosis and extent of tumor resection were observed. The overall survivals of the adjusted Heidelberg scheme matched with the definition of each risk subgroups. Somatic mutations in DNA damage response were detected. Five patients with SHH MB presented potential genetic predisposition and three patients had related germline mutations. Conclusion: The findings of this study provide valuable information for adaptive risk stratified treatment and personalized care of childhood MBs in our cohort series and in Taiwan.
2022-05-18 | GSE143940 | GEO
Project description:Background: Since 2016, a project for molecular diagnosis of childhood medulloblastoma (MB) was initiated in Taiwan. We aimed to integrate molecular classification, molecular and clinical risk factors, somatic mutations, and phenotypic traits for up to date adaptive care. Method: 18 MBs in children with frozen tumor tissue were assembled. Clinical data were retrieved. RNA-Seq and DNA methylation array data were generated. Molecular subgrouping and molecular-clinical correlation were performed. Subgroup-based risk stratification included an adjusted Heidelberg risk stratification scheme were defined and evaluated. We selected 51 genes for somatic variant calling using RNA-Seq. Relevant phenotypic traits were defined for the linkage of genetic predisposition. Results: Four core molecular subgroups (WNT, SHH, Group 3, and Group 4) were identified. Genetic backgrounds of metastasis at diagnosis and extent of tumor resection were observed. The overall survivals of the adjusted Heidelberg scheme matched with the definition of each risk subgroups. Somatic mutations in DNA damage response were detected. Conclusion: The findings of this study provide valuable information for adaptive risk stratified treatment and personalized care of childhood MBs in our cohort series and in Taiwan.
2022-05-18 | GSE158413 | GEO
Project description:We have characterized the transcriptional program regulated by ETV5 at the invasive front of endometrial carcinomas, by comparing it with non-invasive areas of the same tumor samples. In total 12 samples; 6 superficial (non-invasive) tumor areas and the corresponding invasive tumor zones.
2014-11-05 | E-GEOD-57870 | biostudies-arrayexpress
Project description:We developed TARGET-seq, a single-cell genotyping and RNA-seq method, which allows accurate detection of multiple mutations within single-cells from genomic and coding DNA in parallel with whole transcriptome analysis, providing a powerful tool to link transcriptional and genetic tumor heterogeneity. Single cell whole transcriptome sequencing of Lineage-CD34+ HSPC (Hematopoietic Stem and Progenitor Cells) from patients with myeloproliferative neoplasms and normal controls using full-length TARGET-seq reveals distinct molecular signatures associated with the presence of somatic mutations in single cells as well as distinct transcriptional profiles of WT cells from patient samples as compared with normal controls.
2019-02-11 | GSE105452 | GEO