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Molecular Biomarkers of Obesity and Metformin Response in Endometrial Cancer: Analysis of GOG-0286B

ABSTRACT: Molecular Biomarkers of Obesity and Metformin Response in Endometrial Cancer: Analysis of GOG-0286B

PROVIDER: PRJNA842483 | ENA |

REPOSITORIES: ENA

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Molecular Biomarkers of Obesity and Metformin Response in Endometrial Cancer: Analysis of GOG-0286B

Project description:Molecular Biomarkers of Obesity and Metformin Response in Endometrial Cancer: Analysis of GOG-0286B

| PRJNA842482 | ENA

Comparative Proteomics Indicates Metformin Ameliorates Endometrial Receptivity of infertile women with Endometriosis

Project description:Background: Endometriosis affects approximately 10% of reproductive age women and 30%-50% of infertile women. Decreased endometrial receptivity is mainly responsible for infertile women with minimal/mild endometriosis. Medical therapy to improve fecundity of these women is needed. Metformin is reported to inhibit growth of ectopic lesions in endometriosis, while the effect on eutopic endometrium is unclear. The study was to identify if metformin had effect on eutopic endometrium in women with minimal/mild endometriosis and thus improve their fecundity. Materials and Methods: Paired endometrial tissues of secretory phase from participants with minimal/mild endometriosis were collected before and after two months of metformin treatment and setting metformin-free control. Protein expression profiles of endometrium were analyzed by proteomics. Results: A total of 115 proteins were detected up-regulated after metformin therapy, including Insulin-like growth factor-binding protein 7, α-antitrypsin, apolipoprotein D, Rho GDP-dissociation inhibitor 1, brain form glycogen phosphorylase, and Cathepsin B that associated with endometrial receptivity, while there had no significant changes in controls. These up-regulated markers were validated through target proteomics and further demonstrated with endometriosis mice models. Conclusions: This study revealed that metformin might ameliorate biomarkers expressions of endometrial receptivity in human and mice model. Metformin is potential to improve endometrial receptivity of endometriosis-associated infertility.

2021-07-29 | PXD027648 |

The effect of obesity on uterine receptivity is mediated by endometrial extracellular vesicles that control human endometrial stromal cell decidualization and trophoblast invasion

Project description:The objectives of the present study were to determine whether obesity impacts human decidualization and the endometrial control of trophoblast invasion (both of which are required for embryo implantation) and evaluate the potential involvement of endometrial extracellular vesicles (EVs) in the regulation of these physiological processes. Using primary human cell cultures, we first demonstrated that obesity is associated with significantly lower in vitro decidualization of endometrial stromal cells (ESCs). We then showed that the trophoblastic cell line’s invasive ability was greater in the presence of conditioned media from cultures of ESCs from obese women. Using mass-spectrometry-based quantitative proteomics, we found that EVs isolated from uterine supernatants of biopsies from obese women (vs. nonobese women) presented a molecular signature focused on cell remodeling and angiogenesis. Lastly, the results of functional assays indicated that supplementation of the culture medium with EVs from nonobese women can rescue (at least in part) the defect in in vitro decidualization described in ESCs from obese women. Lastly, the addition of endometrial EVs from obese women (vs. nonobese women) was associated with significantly greater invasive activity by HTR-8/SVneo cells. In conclusion, our results provided new insights into the endometrial EVs’ pivotal role in the poor uterine receptivity observed in obese women.

2023-10-09 | PXD039568 | Pride

MP2PRT Genomic and molecular characterization of biomarkers associated with self reported race/ethnicity in high risk endometrial cancers from NRG Oncology/GOG protocol 210, molecular staging of endometrial cancer

Project description:MP2PRT Genomic and molecular characterization of biomarkers associated with self reported race/ethnicity in high risk endometrial cancers from NRG Oncology/GOG protocol 210, molecular staging of endometrial cancer

| PRJNA850071 | ENA

Investigation of placental gene expression in obese women exposed to Metformin during pregnancy

Project description:Maternal obesity in pregnancy is associated with increased birth-weight, obesity and premature mortality in adult offspring. The Effect of Metformin on Maternal and Fetal Outcomes in Pregnant Obese Women (EMPOWaR) trial was a randomised, double-blind, placebo-controlled trial carried out to determine whether exposure to Metformin would affect the offspring birth-weight centile. Obese women exposed to Metformin had increased insulin sensitivity at 36 weeks of pregnancy, but there were no differences in offspring birthweight. We obtained the placentas from these women to determine whether there were differences in expression of genes regulating fetal growth and metabolism. In a complementary study we investigated DNA methylation in the same samples.

2019-01-31 | E-MTAB-6418 | biostudies-arrayexpress

Investigation of placental DNA methylation in obese women exposed to Metformin during pregnancy

Project description:Maternal obesity in pregnancy is associated with increased birth-weight, obesity and premature mortality in adult offspring. The Effect of Metformin on Maternal and Fetal Outcomes in Pregnant Obese Women (EMPOWaR) trial was a randomised, double-blind, placebo-controlled trial carried out to determine whether exposure to Metformin would affect the offspring birth-weight centile. Obese women exposed to Metformin had increased insulin sensitivity at 36 weeks of pregnancy, but there were no differences in offspring birthweight. We obtained the placentas from these women to determine whether there were differences in DNA methylation of genes regulating fetal growth and metabolism. In a related study we investigated the gene expression in the same samples.

2018-11-01 | E-MTAB-6421 | biostudies-arrayexpress

Biomarkers in Samples From Patients With Endometrial Cancer

Project description:This research study is studying biomarkers in samples from patients with endometrial cancer. Studying samples from patients with cancer in the laboratory may help doctors learn more about changes that occur in DNA and identify biomarkers related to cancer.

| 2094895 | ecrin-mdr-crc

Serum lipidomics study looking for specific endometrial polyps biomarkers distinguishing from endometrial cancer or hyperplasia

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

Metformin alters DNA methylation genome-wide via the H19/SAHH axis

Project description:To determine whether exposure of endometrial cancer cells to metformin would induce changes in global DNA methylation, ARK2 cells were incubated with metformin for 48 h, followed by genome-scale DNA methylation profiling using platform of an improved version of Reduced Representation Bisulfite Sequencing (RRBS). Metformin treatment led to extensive methylation changes genome-wide compared to control-treated cells. We found 2000 genes became hypermethylated, and 2000 genes became hypomethylated in ARK2 treatment group.

2016-09-01 | GSE85974 | GEO

Effect of Metformin on Biomarkers of Colorectal Tumor Cell Growth

Project description:The purpose of this study is to investigate the effects of short term oral Metformin therapy on biomarkers for tumor growth in subjects with newly diagnosed colon or rectal adenocarcinoma. It is hypothesized that there are independent actions of Metformin on the outcome of subjects with colorectal cancer (CRC). Also hypothesized is that metformin effects on CRC cell growth will correlate with this drug’s effects on markers mentioned above, because the markers are closely related to tumor growth and metastases.

| 2127916 | ecrin-mdr-crc

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