Dataset Information

Cyclooxygenase-2 and ?-Catenin as Potential Diagnostic and Prognostic Markers in Endometrial Cancer.

ABSTRACT: Objectives: Explore the diagnostic and prognostic value of cyclooxygenase-2 and wnt3a/?-catenin pathway in endometrial cancer. Methods: A prospective cohort study of 93 women underwent hysterectomy at the China-Japan Friendship Hospital (61 patients with primary endometrial carcinoma, and 32 control patients with uterine prolapse or leiomyoma of uterus). Cox2 and ?-catenin expression were determined by immunohistochemistry. The serum levels of cox2 and wnt3a were detected via ELISA assays. Results: Patients with endometrial cancer showed overexpression of cox2 and ?-catenin, as well as significantly higher serum levels of cox2 and wnt3a. The serum cox2 level, which is highly significant in predicting the risk of disease progression (RR, 9.617, 95% confidence interval, 1.162-79.622, P = 0.036), showed good diagnostic and prognostic potential, with cut-off of 55 U/L, but alongside ?-catenin expression in tissues, were related to poor prognosis (RR, 12.426; 95% confidence interval, 1.618-95.450; P = 0.015). Conclusion: Serum levels of cox2 and wnt3a exhibited diagnostic value for endometrial cancer. Cox2 serum levels and ?-catenin expression also showed potential value of prognostic prediction. Cox2 serum levels might be a potential marker for early diagnosis and prognosis prediction in endometrial cancer.

SUBMITTER: Deng L

PROVIDER: S-EPMC7046792 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Cyclooxygenase-2 and β-Catenin as Potential Diagnostic and Prognostic Markers in Endometrial Cancer.

Deng Lin L Liang Haiyan H Han Yi Y

Frontiers in oncology 20200221

<b>Objectives:</b> Explore the diagnostic and prognostic value of cyclooxygenase-2 and wnt3a/β-catenin pathway in endometrial cancer. <b>Methods:</b> A prospective cohort study of 93 women underwent hysterectomy at the China-Japan Friendship Hospital (61 patients with primary endometrial carcinoma, and 32 control patients with uterine prolapse or leiomyoma of uterus). Cox2 and β-catenin expression were determined by immunohistochemistry. The serum levels of cox2 and wnt3a were detected via ELISA ...[more]

PMID: 32154162

Similar Datasets

Project description:The cadherin-catenin proteins have in common with heat shock proteins (HSP) the capacity to bind/interact proteins of other classes. Moreover, there are common molecular pathways that connect the HSP response and the cadherin-catenin protein system. In the present study, we have explored whether in breast cancer the HSP might interact functionally with the cadherin-catenin cell adhesion system. Beta-catenin was immunoprecipitated from breast cancer biopsy samples, and the protein complexes isolated in this way were probed with antibodies against HSP family members. We are thus the first to demonstrate a specific interaction between beta-catenin and Hsp27. However, beta-catenin did not bind Hsp60, Hsp70, Hsp90, gp96, or the endoplasmic reticulum stress response protein CHOP. To confirm the finding of Hsp27-beta-catenin interaction, the 27-kDa immunoprecipitated band was excised from one-dimensional polyacrylamide gel electrophoresis gels and submitted to liquid chromatography-tandem mass spectrometry with electrospray ionization, confirming a role for Hsp27. In addition, beta-catenin interacted with other proteins including heat shock transcription factor 1, P-cadherin, and caveolin-1. In human breast cancer biopsy samples, beta-catenin was coexpressed in the same tumor areas and in the same tumor cells that expressed Hsp27. However, this coexpression was strong when beta-catenin was present in the cytoplasm of the tumor cells and not when beta-catenin was expressed at the cell surface only. Furthermore, murine breast cancer cells transfected with hsp25 showed a redistribution of beta-catenin from the cell membrane to the cytoplasm. When the prognostic significance of cadherin-catenin expression was examined by immunohistochemistry in breast cancer patients (n = 215, follow-up = >10 years), we found that the disease-free survival and overall survival were significantly shorter for patients expressing P-cadherin and for patients showing expression of beta-catenin in the cytoplasm only (not at the cell surface). The interactions of beta-catenin with Hsp27 and with HSF1 may explain some of the molecular pathways that influence tumor cell survival and the clinical significance in the prognosis of the breast cancer patients.

Project description:Objective: Cyclooxygenase-2 (COX-2) is a critical enzyme associated with inflammation and tumorigenesis. Although several studies have compared the expression of COX-2 in endometrial cancer tissues and normal tissues, the results have been inconsistent thus far. This study aims to conduct a meta-analysis to elucidate the role of COX-2 in the determination of the risk, prognosis, and clinical features of endometrial cancer. Methods: We retrieved the suitable studies on the association between COX-2 expression and endometrial cancer from PubMed, EMBASE, and Web of Science databases that were published between 1999 and September 31st, 2019. The hazard ratio (HR) and 95% confidence intervals (CIs) were retrieved to assess the relationship between COX-2 expression and the prognosis of endometrial cancer. The odds ratio (OR) and 95% CIs were calculated to evaluate the correlation between COX-2 expression and the risk and clinical features of endometrial cancer. Results: To investigate the association between COX-2 expression and the susceptibility, clinical features, and prognosis of endometrial cancer, we performed a meta-analysis on data from selected studies that collectively involved 273 normal individuals and 1,376 patients with endometrial cancer. Overall, the pooled analysis indicated that COX-2 expression was significantly associated with susceptibility (Caucasians, OR = 3.94, 95% CI = 2.17-7.17, P < 0.05; Asians, OR = 20.51, 95% CI = 8.54-49.26, P < 0.05), cancer stage (OR = 3.01, 95% CI = 1.95-4.67, P < 0.05), myometrial invasion (OR = 1.59, 95% CI = 1.17-2.15, P < 0.05), lymph node metastasis (OR = 1.63, 95% CI = 1.18-2.26, P < 0.05), and prognosis (OR = 2.91, 95% CI = 1.17-4.66, P < 0.05) in endometrial cancer. Conclusions: Our findings suggested that COX-2 overexpression is significantly associated with poor prognosis and advanced clinical features in endometrial cancer. Therefore, COX-2 may function as an effective prognostic biomarker and a potential therapeutic target for endometrial cancer.

Project description:Rationale: Abnormal Wnt/β-catenin signaling in the endometrium can lead to both embryo implantation failure and severe pathogenic changes of the endometrium such as endometrial cancer and endometriosis. However, how Wnt/β-catenin signaling is regulated in the endometrium remains elusive. We explored possible regulation of Wnt/β-catenin signaling by multi-drug resistance protein 4 (MRP4), a potential target in cancer chemotherapy, and investigated the mechanism. Methods: Knockdown of MRP4 was performed in human endometrial cells in vitro or in a mouse embryo-implantation model in vivo. Immunoprecipitation, immunoblotting and immunofluorescence were used to assess protein interaction and stability. Wnt/β-catenin signaling was assessed by TOPflash reporter assay and quantitative PCR array. Normal and endometriotic human endometrial tissues were examined. Data from human microarray or RNAseq databases of more than 100 participants with endometriosis, endometrial cancer or IVF were analyzed. In vitro and in vivo tumorigenesis was performed. Results: MRP4-knockdown, but not its transporter-function-inhibition, accelerates β-catenin degradation in human endometrial cells. MRP4 and β-catenin are co-localized and co-immunoprecipitated in mouse and human endometrium. MRP4-knockdown in mouse uterus reduces β-catenin levels, downregulates a series of Wnt/β-catenin target genes and impairs embryo implantation, which are all reversed by blocking β-catenin degradation. Analysis of human endometrial biopsy samples and available databases reveals significant and positive correlations of MRP4 with β-catenin and Wnt/β-catenin target genes in the receptive endometrium in IVF, ectopic endometriotic lesions and endometrial cancers. Knockdown of MRP4 also inhibits in vitro and in vivo endometrial tumorigenesis. Conclusion: A previously undefined role of MRP4 in stabilizing β-catenin to sustain Wnt/β-catenin signaling in endometrial cells is revealed for both embryo implantation and endometrial disorders, suggesting MRP4 as a theranostic target for endometrial diseases associated with Wnt/β-catenin signaling abnormality.

Dataset Information

Cyclooxygenase-2 and ?-Catenin as Potential Diagnostic and Prognostic Markers in Endometrial Cancer.

Publications

Cyclooxygenase-2 and β-Catenin as Potential Diagnostic and Prognostic Markers in Endometrial Cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets