miR-486-3p Controls the Apoptosis of Endometrial Carcinoma Cells

Our study aimed to discuss the mechanism of miR-486-3p in controlling the apoptosis of endometrial carcinoma (EC) cells. EC cells were divided into NC group, miR-486-3p mimic and miR-486-3p inhibitor group followed by analysis of miR-486-3p level by Real-time PCR, cell proliferation by spectrophotometric method, apoptosis by FCM, cell migration and invasion by Transwell analysis. EC cells showed reduced miR-486-3p level. The EC malignant biological behaviors could be prompted through retraining miR-486-3p level with increased EC cell invasive capacity. DDR1 was a target of miR-486-3p. The variation of tumor activity could be regulated through controlling DDR1 expression. In conclusion, the apoptotic and invasive characteristic of EC cells are restrained after overexpression of miR-486-3p in EC cells through targeting DDR1, indicating that miR-486-3p could be considered to be one kind of brand-new target for the treatment of EC.

Peritumoral Enhancement for the Evaluation of Myometrial Invasion in Low-Risk Endometrial Carcinoma on Dynamic Contrast-Enhanced MRI

ObjectivesTo explore the clinical value of subendometrial enhancement (SEE), irregular thin-layered peritumoral early enhancement (ITLPE) and focal irregular peritumoral early enhancement (FIPE) on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for myometrial invasion in patients with low-risk endometrial carcinoma.MethodsSeventy-seven patients with low-risk endometrial carcinoma who preoperatively underwent DCE-MRI were included. Two radiologists independently evaluated and recorded the occurrences of SEE, ITLPE and FIPE on DCE-MRI in all patients. Interobserver agreement was calculated between the two radiologists, and the relationships between SEE, ITLPE, FIPE, and myometrial invasion were analyzed based on histologic findings. For statistically significant findings, the sensitivity and specificity were calculated, and the differences in myometrial invasion evaluations were analyzed. For those with no statistical significance, images were compared with the histopathologic sections.ResultsInter-observer agreement was good (k = 0.80; 95%CI, 0.577–0.955) for SEE, and very good (k = 0.88; 95%CI, 0.761–0.972) (k = 0.86; 95%CI, 0.739–0.973) for ITLPE and FIPE. After consensus, SEE was identified in 12/77 (15.6%) patients; ITLPE and FIPE were found in 53/77 (68.8%) and 30/77 (39.0%) patients, respectively. SEE and ITLPE were significantly correlated with myometrial infiltration (P = 0.000), but FIPE were not (P = 0.725).The sensitivity and specificity of SEE and ITLPE for myometrial invasion in patients with low-risk endometrial carcinoma were 95.0 and 52.9%, and 85.0 and 88.0%, respectively. The area under the curve (AUC) of SEE and ITLPE for myometrial invasion were 0.740 (95%CI, 0.584–0.896), and 0.866 (95%CI, 0.763–0.970), respectively. The sensitivity and specificity were statistically different between SEE and ITLPE for the detection of myometrial invasion (P = 0.031, 0.016). According to the comparison between FIPE and histopathologic findings, the irregular endomyometrial junction was found in 30/77 (38.9%) cases, 24/30 (80.0%) with myometrial infiltration and 6/30 (20.0%) cases without myometrial infiltration.ConclusionsFIPE was the irregular endomyometrial junction. It can be found in patients with or without myometrial infiltration and may lead to the overestimation of myometrial invasion by SEE on DCE-MRI. ITLPE presented high diagnostic performance and specificity for myometrial invasion in patients with low-risk endometrial carcinoma.

Prognostic significance of CTNNB1 mutation in early stage endometrial carcinoma: a systematic review and meta-analysis

Background In the last years, mutations in the exon 3 of CTNNB1 have emerged as a possible prognostic factor for recurrence in early stage endometrioid endometrial carcinoma, especially in cases with no specific molecular profile (NSMP). Objective To define the prognostic value of CTNNB1 mutations in early stage endometrioid endometrial carcinoma, through a systematic review and meta-analysis. Methods Electronic databases were searched from their inception to November 2020 for all studies assessing the prognostic value of CTNNB1 mutation in early stage (FIGO I–II) endometrioid endometrial carcinoma. Odds ratio (OR) for tumor recurrence and hazard ratio (HR) for disease-free survival (DFS) were calculated with a significant p value < 0.05. Results Seven studies with 1031 patients were included. Four studies were suitable for meta-analysis of OR and showed significant association between CTNNB1 mutation and the absolute number of recurrence (OR = 3.000; p = 0.019); the association became stronger after excluding patients with known molecular status other than NSMP (HR = 5.953; p = 0.012). Three studies were suitable for meta-analysis of HR and showed no significant association between CTNNB1 mutation and decreased DFS (HR = 1.847; p = 0.303); the association became significant after excluding patients with known molecular status other than NSMP (HR = 2.831; p = 0.026). Conclusion CTNNB1 mutation is significantly associated with recurrence in early stage endometrioid endometrial carcinomas, especially in the NSMP, appearing potentially useful in directing adjuvant treatment.

Elevated Expression of Gamma-Glutamyl Hydrolase Is Associated With Poor Prognosis and Altered Immune Signature in Uterine Corpus Endometrial Carcinoma

Uterine corpus endometrial carcinoma (UCEC) is a common malignant tumor of the female reproductive system with poor prognosis in advanced, recurrent, and metastatic cases. Identification of reliable molecular markers will help in the development of clinical strategies for early detection, diagnosis, and intervention. Gamma-glutamyl hydrolase (GGH) is a key enzyme in folate metabolism pathway. High expression of GGH is associated with severe clinicopathological features and poor prognosis of several cancers. High GGH expression is also related to cell resistance to antifolate drugs such as methotrexate. In this study we focused on the prognostic value of immunohistochemical GGH expression level in UCEC tissue and RNA-seq data from The Cancer Genome Atlas to establish associations with clinical features and outcomes. Further, we conducted comprehensive bioinformatics analyses to identify and functionally annotate differentially expressed genes (DEGs) associated with UCEC upregulation and assessed the effects of upregulation on immune infiltration. Both GGH mRNA and protein expression levels were elevated in tumor tissues, and higher expression was significantly associated with advanced clinicopathological features and poor prognosis by univariate analysis. Further multivariate analysis identified elevated GGH expression as an independent risk factor for poor outcome. Nomograms including GGH expression yielded a c-index for disease-specific survival prediction of 0.884 (95% confidence interval: 0.861–0.907). A total of 520 DEGs (111 upregulated and 409 downregulated) were identified between high and low GGH expression groups. Analysis using Gene ontology, Kyoto Encyclopedia of Genes and Genomes pathway, Gene set enrichment analysis, and protein‒protein interaction indicated significant associations of altered GGH expression with cell proliferation, immune response, and the occurrence and development of UCEC tumors. Finally, GGH expression level was associated with high Th2 cell and low natural killer CD56bright cell infiltration. Collectively, these findings indicate that GGH drives UCEC progression and could be a useful biomarker for survival prediction as well as a therapeutic target.

Endometrial sampling tests for the diagnosis of endometrial carcinoma: a protocol of a diagnostic test accuracy systematic review

Background: Endometrial cancer ranks as the most common gynecological cancer. An accurate detection can dramatically improve patient relevant outcomes.Objectives: To determine the diagnostic accuracy of different endometrial sampling methods for detecting endometrial carcinoma and its precursors.Search strategy: we will search the Cochrane library, Pubmed/MEDLINE, Web of Science, and Scopus. We will search references of relevant studies.Selection criteria: We will include diagnostic test accuracy studies if women had an endometrial sampling followed by verification with histopathology in hysterectomy specimens. The primary target is endometrial carcinoma.Data collection and analysis: Two authors will independently screen studies, extract data, and assess methodological quality. We will use bivariate diagnostic random-effects meta-analysis.Results: This is a protocol of a diagnostic test accuracy systematic review.Conclusions: Evidence will aid in making well-informed decisions for diagnosing endometrial carcinoma. Implications for research will be outlined for future studies.