ABSTRACT
Purpose: To evaluate the impact of embryo banking on the cumulative live birth rate (CLBR) and the time to live birth (TTLB) in poor ovarian responders (POR) according to the Bologna criteria. Methods: A total of 276 infertile women undergoing IVF with POR were included in this retrospective study. They were divided into two groups with (n = 121) or without (n = 155) embryo banking at the discretion of the attending physicians. A total of 656 and 405 stimulation cycles were started in the two groups respectively during the 24 month follow-up. Results: The biochemical pregnancy, clinical pregnancy, ongoing pregnancy, and live birth rate per transfer were comparable between two groups (p > 0.05). The CLBR was significantly lower in the banking group than in the non-banking group (31.4% (38/121) and 43.2% (67/151), p < 0.05). TTLB was significantly longer in the banking group (20.5 months vs. 16.0 months, p < 0.001). In the Kaplan-Meier analysis, the cumulative incidence of live birth was significantly lower in the banking group compared with the non-banking group (Log rank test, chi-square = 21.958, p < 0.001). Conclusions: Embryo banking in women undergoing IVF with POR based on the Bologna criteria reduces CLBR and lengthens TTLB when compared with no embryo banking.
ABSTRACT
3ß-Hydroxysteroid-Δ24 reductase (DHCR24), the final enzyme of the cholesterol biosynthetic pathway, has been associated with urogenital neoplasms. However, the function of DHCR24 in endometrial cancer (EC) remains largely elusive. Here, we analyzed the expression profile of DHCR24 and the progesterone receptor (PGR) in our tissue microarray of EC (n = 258), the existing EC database in GEO (Gene Expression Omnibus), and TCGA (The Cancer Genome Atlas). We found that DHCR24 was significantly elevated in patients with EC, and that the up-regulation of DHCR24 was associated with advanced clinical stage, histological grading, vascular invasion, lymphatic metastasis, and reduced overall survival. In addition, DHCR24 expression could be induced by insulin though STAT3, which directly binds to the promoter elements of DHCR24, as demonstrated by ChIP-PCR and luciferase assays. Furthermore, genetically silencing DHCR24 inhibited the metastatic ability of endometrial cancer cells and up-regulated PGR expression, which made cells more sensitive to progestin. Taken together, we have demonstrated for the first time the crucial role of the insulin/STAT3/DHCR24/PGR axis in the progression of EC by modulating the metastasis and progesterone response, which could serve as potential therapeutic targets for the treatment of EC with progesterone receptor loss.
Subject(s)
Endometrial Neoplasms/enzymology , Endometrial Neoplasms/pathology , Endometrium/abnormalities , Insulin/adverse effects , Nerve Tissue Proteins/biosynthesis , Oxidoreductases Acting on CH-CH Group Donors/biosynthesis , Up-Regulation/genetics , Uterine Diseases/enzymology , Aged , Cell Line, Tumor , Cell Movement/drug effects , Endometrial Neoplasms/drug therapy , Endometrial Neoplasms/genetics , Endometrium/enzymology , Endometrium/pathology , Enzyme Induction/drug effects , Female , Gene Expression Regulation, Neoplastic/drug effects , Gene Silencing/drug effects , Humans , Medroxyprogesterone Acetate/pharmacology , Medroxyprogesterone Acetate/therapeutic use , Middle Aged , Neoplasm Invasiveness , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/metabolism , Oxidoreductases Acting on CH-CH Group Donors/genetics , Oxidoreductases Acting on CH-CH Group Donors/metabolism , Prognosis , Receptors, Progesterone/genetics , Receptors, Progesterone/metabolism , STAT3 Transcription Factor/metabolism , Up-Regulation/drug effects , Uterine Diseases/genetics , Uterine Diseases/pathologyABSTRACT
Dysfunction of nuclear factor-κB (NF-κB) signaling has been causally associated with numerous human malignancies. Although the NF-κB family of genes has been implicated in endometrial carcinogenesis, information regarding the involvement of central regulators of NF-κB signaling in human endometrial cancer (EC) is limited. Here, we investigated the specific roles of canonical and noncanonical NF-κB signaling in endometrial tumorigenesis. We found that NF-κB RelB protein, but not RelA, displayed high expression in EC samples and cell lines, with predominant elevation in endometrioid adenocarcinoma (EEC). Moreover, tumor cell-intrinsic RelB was responsible for the abundant levels of c-Myc, cyclin D1, Bcl-2 and Bcl-xL, which are key regulators of cell cycle transition, apoptosis and proliferation in EEC. In contrast, p27 expression was enhanced by RelB depletion. Thus, increased RelB in human EC is associated with enhanced EEC cell growth, leading to endometrial cell tumorigenicity. Our results reveal that regulatory RelB in noncanonical NF-κB signaling may serve as a therapeutic target to block EC initiation.
Subject(s)
Carcinogenesis/metabolism , Carcinogenesis/pathology , Carcinoma, Endometrioid/metabolism , Carcinoma, Endometrioid/pathology , Cell Cycle , NF-kappa B/metabolism , Transcription Factor RelA/metabolism , Transcription Factor RelB/metabolism , Animals , Apoptosis/genetics , Cell Cycle Checkpoints/genetics , Cell Line, Tumor , Cell Proliferation , Female , G1 Phase/genetics , Humans , Mice, Inbred BALB C , Middle Aged , Neoplasm Staging , Phenotype , S Phase/genetics , Signal Transduction/geneticsABSTRACT
Early-stage endometrial carcinoma (EC) patients have a high cure rate; however, those with high-risk factors may have poor prognosis. Thus, there is an urgent need for searching for new prognostic molecules to more accurately predict survival of patients. We detected the Rictor mRNA expression level in 30 fresh EC tissue and 17 normal endometrial tissue samples with real-time quantitative RT-PCR and Rictor protein expression level in 134 (test cohort) and 115 (validation cohort) paraffin tissue samples by immunohistochemistry, analyzed the correlation between variables and overall survival (OS) using Cox proportional hazards regression, compared the prognostic accuracy of Rictor with other clinicopathological risk factors by logistic regression. The results showed that Rictor mRNA expression of EC is higher than that of normal endometrium; Rictor protein expression level was closely correlated with FIGO stage, grade and vascular invasion in both cohorts; a univariate analysis showed that the pathological type, stage, grade, vascular invasion, lymphatic metastasis and Rictor were predictors of OS in both cohorts; furthermore, multivariate Cox proportional hazards regression analysis indicated that vascular invasion and Rictor were independent prognostic factors for EC in both cohorts; an ROX curve comparison showed that the area under the curve (AUC) for Rictor combined with other clinicopathological prognostic factors was higher than any individual factor or other clinicopathological prognostic factors' combination. Based on the above data, we concluded that Rictor is an independent prognostic factor for EC. It combined with other clinicopathological risk factors was a stronger prognostic model than individual risk factor or their combination.
Subject(s)
Biomarkers, Tumor/analysis , Carcinoma/chemistry , Carrier Proteins/analysis , Endometrial Neoplasms/chemistry , Biomarkers, Tumor/genetics , Biopsy , Carcinoma/genetics , Carcinoma/mortality , Carcinoma/pathology , Carrier Proteins/genetics , Chi-Square Distribution , Endometrial Neoplasms/genetics , Endometrial Neoplasms/mortality , Endometrial Neoplasms/pathology , Female , Humans , Immunohistochemistry , Kaplan-Meier Estimate , Logistic Models , Multivariate Analysis , Neoplasm Grading , Neoplasm Invasiveness , Neoplasm Staging , Proportional Hazards Models , RNA, Messenger/analysis , Rapamycin-Insensitive Companion of mTOR Protein , Real-Time Polymerase Chain Reaction , Retrospective Studies , Risk Factors , Time Factors , Up-RegulationABSTRACT
Endometrial cancer (EC) is one of the most common female malignancies. The patients with high-risk factors may have poor prognosis. Therefore, there is an urgent need to find a new molecule to more accurately predict survival of patients. Leucine-rich-alpha-2-glycoprotein1 (LRG1), one of leucine-rich repeat family, was closely associated with cancer metastasis and poor prognosis. The biological functions and the expression level of LRG1 remain obscure in EC. In this study, by immunohistochemical analysis of 242 EC patient tissues, we found that LRG1 expression was associated with stage and lymphatic metastasis in both test cohort (133 patients) and validation cohort (109 patients). Furthermore, to investigate the prognostic value of LRG1 in endometrial carcinoma, we analyzed the correlation between variables and overall survival with Cox proportional hazard regression. The result showed that LRG1 was an independent prognostic factor for overall survival of endometrial carcinoma patients. To further evaluate the prognostic efficiency of LRG1 in endometrial carcinoma, we compared the sensitivity and specificity of LRG1 in endometrial carcinoma prognosis by logistic regression. The result showed that LRG1 combining with other clinicopathological risk factors was a stronger prognostic model than clinicopathological risk factors alone or their combination. Thus, LRG1 potentially offered clinical value in directing personal treatment for endometrial carcinoma patients.
