Discovering New Targets for Colorectal and Endometrial Cancer Risk Reduction
Ontology highlight
ABSTRACT:
DISEASE(S): Endometrial Cancer,Colorectal Cancer,Hereditary Cancer Syndromes,Endometrial Neoplasms,Neoplastic Syndromes, Hereditary
PROVIDER: 114407 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
Similar Datasets
Project description:Competent endometrial receptivity is a prerequisite for successful embryo implantation. Identification of novel key molecules involved in endometrial receptivity is essential to better interpret human implantation and improve pregnancy rates in assisted reproduction treatment. The isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomics was performed to profile the proteomes of the prereceptive( LH+2, n=4) and receptive (LH+7, n=4) endometrial tissues. One hundred seventy-three differentially expressed proteins (DEPs) between LH+2 and LH+7 endometrial samples were identified. Integrated analysis of the proteomic data and published transcriptomic data was performed to identify the concordant DEPs with differential expression at both mRNA and protein levels. The protein-protein-interaction (PPI) network analysis were performed on concordant DEPs.We first identified 63 novel concordant DEPs and 5 hub proteins (ACSL4, ACSL5, COL1A1, PTGS1 and PLA2G4F) between LH+2 and LH+7 endometrial samples. ACSL4 was predominantly expressed in endometrial epithelial cells and its expression was significantly upregulated in the LH+7 endometrium and significantly downregulated in repeated implantation failure (RIF) patients. Knockdown of ACSL4 in endometrial epithelial cells induced the down-regulation of endometrial receptivity markers (HOXA10, COX2 and LIF) and the significant decrease of implantation rate during in vitro implantation analysis. This study provides the first gel-independent quantitative proteomes of the LH+2 and LH+7 human endometrium using iTRAQ technology. The identified concordant DEPs and hub proteins open a new avenue for future studies aimed at elucidating the underlying mechanisms governing endometrial receptivity. ACSL4 was identified as a novel regulatory molecule in the establishment of endometrial receptivity and might play important roles during implantation.
2023-01-02 | PXD039161 | iProX
Project description:Proper decidualization is vital in preparation for a potential embryo receptivity, placentation, menstrual health and subsequent endometrial regeneration. Given the importance of extracellular vesicles (EVs) in intercellular communication, and recently in embryo implantation and indicators of menstrual cycle and fertility, we investigated their role during decidualization. Overall, this study provides an insight into distinct variation in sEV composition depending upon the level of decidualization of endometrial stromal cells, with the signaling potential to coordinate endometrial health ranging from embryo implantation, facilitating placentation and subsequent endometrial regeneration.
2021-11-17 | PXD026342 | Pride
Project description:<p>Endometrial diseases are common gynecological diseases that disorder women of childbearing age and perimenopausal women, including endometrial polyps (EP), endometrial cancer (EC), and endometrial hyperplasia (EH). Clinically, biopsy or imaging methods are usually used to screen and diagnose endometrial diseases, but due to their invasiveness and heterogeneity, a noninvasive, convenient, objective and accurate biomarker is needed for the differential diagnosis of EP and EC or EH. In the present study, serum samples from 396 patients with endometrial disease and 225 healthy volunteers were analyzed by UPLC-Q-TOF/MS non-targeted lipidomics. A combination of multivariate (Orthogonal partial least-squares discriminant analysis) and univariate (Student t-test) analyses were used to identify and qualify 6, 8, and 7 potential biomarkers in serum from patients with EP, EC, and EH, respectively. With the aid of logistic regression algorithm and receiver operating characteristic (ROC) curve analysis, A biomarker panel including four specific EP biomarkers, 6-Keto-PGF1α, PA(37:4), LysoPC(20:1) and PS (36:0), had good classification and diagnostic ability in distinguishing EP from EC or EH. The biomarker panel can be used as a rapid diagnostic method to assist imaging examination to effectively differentially diagnose endometrial diseases, and provide a reference for clinicians in the identification and diagnosis of endometrial diseases. </p>
2022-01-14 | MTBLS3444 | MetaboLights
Project description:Defective endometrial stromal fibroblasts (EMSF) contribute to uterine factor infertility, endometriosis and endometrial cancer. Induced pluripotent stem cells (iPSC) derived from skin or bone marrow biopsies provide a patient-specific source that can be differentiated to various cells types. Replacement of abnormal EMSF is a potential novel therapeutic approach for endometrial disease; however, the methodology or mechanism for differentiating iPSC to EMSF is unknown. The uterus differentiates from the intermediate mesoderm (IM) to form coelomic epithelium (CE) followed by the Müllerian duct (MD). Here, we successfully directed the differentiation of human iPSC (hiPSC) through IM, CE and MD to EMSF under molecularly defined embryoid body culture conditions using specific hormonal treatments. Activation of CTNNB1 was essential for expression of progesterone receptor that mediated the final differentiation step of EMSF before implantation. These hiPSC-derived tissues illustrated the potential for iPSC-based endometrial regeneration for future cell-based treatments.
2018-10-31 | E-MTAB-7292 | biostudies-arrayexpress
Project description:The molecular events implicated in the development of endometrial carcinosarcoma remain poorly understood. Using complementary DNA microarrays, we analyzed a group of 15 endometrial carcinosarcomas and compared their gene expression profiles with those obtained from a group of 23 endometrioid endometrial carcinomas. We demonstrated changes in the expression of genes modulating processes such as the epithelial to mesenchymal transition, muscle differentiation, the expression of cancer/testis antigens, and immune response in endometrial carcinosarcomas. The high mobility group AT-hook 2 gene is an embryonic nuclear factor that mediates epithelial to mesenchymal transition in various tumor models, and it was among the genes overexpressed in endometrial carcinosarcomas. High mobility group AT-hook 2 overexpression was confirmed in 54% of endometrial carcinosarcomas by quantitative real time-polymerase chain reaction and immunohistochemistry. Moreover, we found a significant inverse correlation between the expression of high mobility group AT-hook 2 and let-7b, a member of the let-7 family of microRNAs that represses high mobility group AT-hook 2 expression. These changes were also associated with overexpression of Lin28B, a suppressor of microRNA biogenesis that is implicated in cancer progression and metastasis. Finally, high mobility group AT-hook 2 overexpression, which was detected in less than 3% of endometrioid endometrial carcinomas, was observed in many nonendometrioid carcinomas (46% of 28 samples). This pattern of expression, restricted to nonendometrioid carcinomas and endometrial carcinosarcomas, reflects a role for high mobility group AT-hook 2 in endometrial carcinogenesis that is associated with aggressive phenotypes and points to its potential use as a marker to distinguish between endometrioid and nonendometrioid tumors.
2012-11-01 | GSE33723 | GEO
Project description:The gut-uterus axis plays a pivotal role in the pathogenesis of endometrial cancer (EC). However, the correlations between the endometrial microbiome and endometrial tumor transcriptome in patients with EC and the impact of the endometrial microbiota on hematological indicators have not been thoroughly clarified. In this prospective study, endometrial tissue samples collected from EC patients (n = 30) and healthy volunteers (n = 10) were subjected to 16S rRNA sequencing of the microbiome. The 30 paired tumor and adjacent nontumor endometrial tissues from the EC group were subjected to RNAseq. Result: We found that Pelomonas and Prevotella were enriched in the EC group with a high tumor burden. Further transcriptome analysis identified 8 robust associations between Prevotella and fibrin degradation-related genes expressed within ECs. Conclusions: Our results suggest that the increasing abundance of Prevotella in endometrial tissue combined with high serum DD and FDP contents may be important factors associated with tumor burden.
2021-10-13 | GSE183185 | GEO
Project description:After informed consent, participants will be asked to complete a medical/family history questionnaire and provide a blood sample. Participants will also be asked for their permission for study investigators to access medical records and/or recontact them for updates to their medical and family histories. Data and biospecimens will be stored for potential future research projects.
| 2052012 | ecrin-mdr-crc
Project description:The molecular events that mediate the epithelial to mesenchymal transition (EMT) in endometrial cancer remain poorly understood. Using cDNA microarrays, we analyzed a group of endometrial carcinosarcomas (ECS), a true example of EMT in vivo, and we compared their gene expression profiles with those obtained from a group of endometrioid endometrial carcinomas (EEC). The HMGA2 gene (High Mobility Group AT-hook 2), an embryonic nuclear factor that mediates EMT in various tumour models, was among the genes overexpressed in ECS, and HMGA2 overexpression was confirmed in 54% of ECSs by qRT-PCR and immunohistochemistry. Moreover, we found a significant inverse correlation between the expression of HMGA2 and let-7b, a member of the let-7 family of miRNAs that represses HMGA2 expression. These changes were also associated with overexpression of Lin28B, a suppressor of microRNA biogenesis implicated in cancer progression and metastasis. Finally, HMGA2 overexpression, which was detected in less than 3% of EECs, was observed in many non-endometrioid carcinomas (46%). For the first time, we describe a role for HMGA2 in both the process of EMT that contributes to endometrial carcinogenesis and in the acquisition of aggressive phenotypes by this neoplasia. Moreover, we demonstrate changes in the expression of genes modulating processes such as EMT, muscle differentiation, the expression of cancer testis antigens (CTAs) and the immune response. Identification of new molecular markers in endometrial carcinogenesis 15 endometrial carcinosarcomas and 23 endometrioid endometrial carcinoma
2012-11-01 | E-GEOD-33723 | biostudies-arrayexpress
Project description:We tested the hypothesis that a panel of placental mammal-specific miRNAs and their targets play important to establish receptivity to implantation and their dysregulated expression may be a feature in women with early pregnancy loss. Relative expression levels of miR-340-5p, −542-3p, and −671-5p all increased following treatment of Ishikawa cells with progesterone (10 μg/ml) for 24 hrs (p < 0.05). RNA sequencing of these P4-treated cells identified co-ordinate changes to 6,367 transcripts of which 1713 were predicted targets of miR-340-5p, 670 of miR-542-3p, and 618 of miR-671-5p. Quantitative proteomic analysis of Ishikawa cells transfected with mimic or inhibitor (48 hrs: n=3 biological replicates) for each of the P4-regulated miRNAs was carried out to identify targets of these miRNAs. Excluding off target effects, mir-340-5p mimic altered 1,369 proteins while inhibition changed expression of 376 proteins (p < 0.05) of which, 72 were common to both treatments. A total of 280 proteins were identified between predicted (mirDB) and confirmed (in vitro) targets. In total, 171 proteins predicted to be targets by mirDB were altered in vitro by treatment with miR-340-5p mimic or inhibitor and were also altered by treatment of endometrial epithelial cells with P4. In vitro targets of miR-542-3p identified 1,378 proteins altered by mimic while inhibition altered 975 a core of 200 proteins were changed by both. 100 protein targets were predicted and only 46 proteins were P4 regulated. miR-671-mimic altered 1,252 proteins with inhibition changing 492 proteins of which 97 were common to both, 95 were miDB predicted targets and 46 were also P4-regulated. All miRNAs were detected in endometrial biopsies taken from patients during the luteal phase of their cycle, irrespective of prior or future pregnancy outcomes Expression of mir-340-5p showed an overall increase in patients who had previously suffered a miscarriage and had a subsequent miscarriage, as compared to those who had infertility or previous miscarriage and subsequently went on to have a life birth outcome. The regulation of these miRNAs and their protein targets regulate the function of transport and secretion, and adhesion of the endometrial epithelia required for successful implantation in humans. Dysfunction of these miRNAs (and therefore the targets they regulate) may contribute to endometrial-derived recurrent pregnancy loss in women.
2023-05-10 | PXD036109 | Pride