Overall Survival In Endometrial Cancer Patients Research Articles

High PLK3 levels are linked with less tumor invasion, lower FIGO stage and better prognosis of endometrial cancer.

Aim: To evaluate correlations of tumor PLK3with clinical features and prognosis of resectable endometrial cancer (EC) patients.Methods: Tumor tissues from 200 EC patients receiving surgical resections and adjacent tissues from 50 of them were collected for PLK3 determination using immunohistochemistry.Results: Tumor PLK3 negatively linked with myometrial invasion ≥50%, lymphovascular invasion, stromal cervical invasion, and International Federation of Gynecology and Obstetrics stage (all p <0.050). High tumor PLK3 independently related to longer disease-free survival (DFS) (p=0.044) and overall survival (OS) (p=0.049). Its prognostic value was also validated by time-dependent receiver operating characteristic analyses (area under curve at most timepoints was >0.700).Conclusion: Tumor PLK3 potentially reflects prolonged DFS and OS in EC patients undergoing surgical resections.

Abstract 249: Deciphering the impact of TRIB3-ELF4 interaction in regulating CDK6 on cancer stem cell activity in endometrial cancer

Abstract Background: Endometrial cancer (EC) is the most common gynecological tumor among women worldwide, posing a serious threat to women's health. ELF4 (E74 like ETS transcription factor 4), a member of the ETS family, plays a role in facilitating cancer progression. Our previous work demonstrated the role of direct binding between ELF4 and tribbles pseudokinase 3 (TRIB3) in promoting β-catenin expression. In this study, we further explore ELF4's involvement in the maintenance of cancer stem cells (CSCs) in EC. Methods: The vital role of ELF4 in EC was determined through gain- and loss-of-function assays. ELF4 was silenced in two EC cell lines, AN3CA and HEC-1A, and primary EC cells from a Taiwanese patient (EMC6), using RNA interference techniques. The expression of ELF4, TRIB3, and CDK6 in human EC samples was assessed using immunohistochemistry. Tumorsphere formation assays, quantitative real-time PCR, and immunoblotting quantified CSC activity and the involvement of related signaling pathways. Transcriptional regulation associated with ELF4 was investigated using luciferase reporter assays and chromatin immunoprecipitation. Results: Analysis of the TCGA database via the TISIDB web tool revealed that elevated ELF4 levels correlated with higher histological grades, advanced clinical stages, and poorer overall survival in EC patients. A grade-dependent increase in ELF4 expression was observed using tissue microarrays. Knockdown of ELF4 in EC cell lines and patient-derived EC cells significantly reduced cell proliferation, cell cycle progression, migration, invasion, and CSC activity. RNA-seq data analysis of ELF4-knockdown EC cells identified CDK6 as a potential downstream target of the ELF4/TRIB3 interaction. Knockdown of ELF4 and TRIB3 significantly downregulated CDK6 expression. Co-expression of TRIB3 and ELF4 enhanced CDK6 expression, and their expression was positively associated with CDK6 in EC specimens. We also demonstrated that CDK6 facilitates EC-CSC activity. Knockdown of CDK6 significantly attenuated tumorsphere formation and reduced the levels of cancer stemness-related proteins, including OCT4, NANOG, and c-MYC. Conclusion: Our study demonstrates the essential roles of ELF4 and TRIB3 in regulating CDK6 expression, contributing to the maintenance of EC-CSCs. Citation Format: Wen-Ling Wang, Wen-Wei Chang. Deciphering the impact of TRIB3-ELF4 interaction in regulating CDK6 on cancer stem cell activity in endometrial cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 249.

Tumor polo-like kinase 4 protein expression reflects lymphovascular invasion, higher Federation of Gynecology and Obstetrics stage, and shortened survival in endometrial cancer patients who undergo surgical resection

BackgroundPolo-like kinase 4 (PLK4) serves as a marker for tumor features and poor outcomes in cancers. This study aimed to explore the associations of tumor PLK4 protein expression with tumor characteristics and survival in endometrial cancer (EC) patients who underwent surgical resection.MethodsThis study included 142 EC patients who underwent surgical resection. Tumor tissue samples were obtained for tumor PLK4 protein expression detection via immunohistochemistry (IHC).ResultsAmong EC patients, 26.1% had a PLK4 IHC score of 0, 24.6% had a score of 1–3, 27.5% had a score of 4–6, and 21.8% had a score of 7–12. Tumor PLK4 protein expression positively associated with lymphovascular invasion (P = 0.008) and Federation of Gynecology and Obstetrics (FIGO) stage (P = 0.005). Disease-free survival (DFS) was not different between patients with tumor PLK4 IHC scores > 0 and ≤ 0 (P = 0.154) but was reduced in patients with scores > 3 vs. ≤ 3 (P = 0.009) and > 6 vs. ≤ 6 (P < 0.001). Similarly, overall survival (OS) was not different between patients with scores > 0 and ≤ 0 (P = 0.322) but was shorter in patients with scores > 3 vs. ≤ 3 (P = 0.011) and > 6 vs. ≤ 6 (P = 0.006). After adjustment, a tumor PLK4 IHC score > 6 (vs. ≤ 6) (hazard ratio (HR): 3.156, P = 0.008) or > 3 (vs. ≤ 3) (HR: 3.918, P = 0.026) was independently associated with shortened DFS and OS.ConclusionA tumor PLK4 IHC score > 6 or > 3 associates with shortened DFS and OS in EC patients who undergo surgical resection.

Identification of HOXB9 to predict prognosis of endometrial cancer based on comprehensive bioinformatics analysis

BackgroundThe HOXB9 gene, which plays a key role in embryonic development, is also involved in the regulation of various human cancers. However, the potential relationship between HOXB9 and endometrial cancer (EC) has not yet been comprehensively analyzed and fully understood.MethodsWe used multiple bioinformatics tools to explore the role of HOXB9 in EC.ResultsThe expression of HOXB9 was significantly upregulated in pan-cancer, including EC (P < 0.05). Quantitative real time polymerase chain reaction (qRT-PCR) experiment confirmed the high expression of HOXB9 in EC from clinical samples (P < 0.001). Double validated by Enrichr and Metascape, HOXB9 showed a strong correlation with HOX family, suggesting that HOX family may also involve in the development of EC (P < 0.05). Enrichment analysis revealed HOXB9 is mainly associated with cellular process, developmental process, P53 signaling pathway, etc. At the single-cell level, the clusters of cells ranked were glandular and luminal cells c-24, glandular and luminal cells c-9, endothelial cells c-15, compared with the other cells. At the genetic level, promoter methylation levels of HOXB9 were significantly higher in tumors than in normal tissues. Furthermore, variations of HOXB9 were closely associated with overall survival (OS) and recurrence free survival (RFS) in EC patients (P < 0.05). The agreement between univariate and multivariate Cox regression indicated that the results were more reliable. Stages III and IV, G2 and G3, tumor invasion ≥ 50%, mixed or serous histological type, age > 60 years, and high expression of HOXB9 were risk factors strongly associated with OS in EC patients (P < 0.05). Therefore, six factors were incorporated to construct a nomogram for survival prediction. Finally, we used the Kaplan-Meier (KM) curve, receiver operating characteristic (ROC) curve, and time-dependent ROC to assess predictive power of HOXB9. KM curve showed EC patients overexpressing HOXB9 had a worse OS. AUC of diagnostic ROC was 0.880. AUCs of time-dependent ROC were 0.602, 0.591, and 0.706 for 1-year, 5-year, and 10-year survival probabilities (P < 0.001).ConclusionsOur study provids new insights into the diagnosis and prognosis of HOXB9 in EC and constructs a model that can accurately predict the prognosis of EC.

MCM2 promotes the stemness of endometrial cancer cells via the Akt/β-catenin pathway.

Minichromosome maintenance complex component 2 (MCM2) is a member of the MCM family and is involved in various cancers. However, the role of MCM2 in endometrial cancer (EC) remains unclear. In this study, we aim to determine the biological function of MCM2 in EC cells and identify the potential underlying mechanisms. MCM2 expression and prognostic significance were analyzed in TCGA-UCEC datasets. Combining bioinformatics analyses and experiments, stemness-related molecules and phenotypes were examined to evaluate the impact of MCM2 on stemness in EC cells. The major findings of these analyses are as follows: 1) MCM2 is expressed at higher levels in EC tissues than in normal endometrial tissues. High expression of MCM2 is related to the characteristics of poorly differentiated EC. High MCM2 expression is correlated with poor overall survival in EC patients; 2) MCM2 knockdown was found to decrease sphere formation ability, downregulate the expression of stemness-related molecules, and reduce the proportion of CD133+ cells, while MCM2 overexpression elicited the opposite effect in EC cells; 3) MCM2-mediated stemness features are dependent on the activation of Akt/β-catenin signaling pathways; and 4) MCM2 knockdown increases cisplatin sensitivity in EC cells. MCM2 regulates stemness by regulating the Akt/β-catenin signaling pathway in EC cells.

DSCAM-AS1 Long Non-Coding RNA Exerts Oncogenic Functions in Endometrial Adenocarcinoma via Activation of a Tumor-Promoting Transcriptome Profile.

Accumulating evidence suggests that lncRNA DSCAM-AS1 acts tumor-promoting in various cancer entities. In breast cancer, DSCAM-AS1 was shown to be the lncRNA being most responsive to induction by estrogen receptor α (ERα). In this study, we examined the function of DSCAM-AS1 in endometrial adenocarcinoma using in silico and different in vitro approaches. Initial analysis of open-source data revealed DSCAM-AS1 overexpression in endometrial cancer (EC) (p < 0.01) and a significant association with shorter overall survival of EC patients (HR = 1.78, p < 0.01). In EC, DSCAM-AS1 was associated with endometrial tumor promotor gene PRL and with expression of ERα and its target genes TFF1 and PGR. Silencing of this lncRNA by RNAi in two EC cell lines was more efficient in ERα-negative HEC-1B cells and reduced their growth and the expression of proliferation activators like NOTCH1, PTK2 and EGR1. DSCAM-AS1 knockdown triggered an anti-tumoral transcriptome response as revealed by Affymetrix microarray analysis, emerging from down-regulation of tumor-promoting genes and induction of tumor-suppressive networks. Finally, several genes regulated upon DSCAM-AS1 silencing in vitro were found to be inversely correlated with this lncRNA in EC tissues. This study clearly suggests an oncogenic function of DSCAM-AS1 in endometrial adenocarcinoma via activation of a tumor-promoting transcriptome profile.

Integrated bioinformatics data analysis reveals a risk signature and PKD1 induced progression in endometrial cancer patients with postmenopausal status.

Background: Endometrial cancer (EC) is one of the most common type of female genital malignancies. The purpose of the present study was to reveal the underlying oncogene and mechanism that played a pivotal role in postmenopausal EC patients.Methods: Weighted gene co-expression network analysis (WGCNA) was conducted using the microarray dataset and clinical data of EC patients from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases to identify significant gene modules and hub genes associated with postmenopausal status in EC patients. LASSO regression was conducted to build and validate the risk model. Finally, expression of hub gene was validated in pre- and post-menopausal EC patients in our center.Results: 1240 common genes were used to construct the WGCNA model. According to the WGCNA results, we identified a brown module with 471 genes which was significantly associated with postmenopausal status in EC patients. Furthermore, we constructed an 11-gene risk signature to predict the overall survival of EC patients. The Kaplan–Meier curve and area under the ROC curve (AUC) of this model showed high accuracy in prediction. We also validate the risk model in patients in our center and it also has a high accuracy. Among the 11 genes, PKD1 was recognized as a potential biomarker in the progression of EC patients with postmenopausal status.Conclusion: Taken together, we uncovered a common PKD1-mediated mechanism underlying postmenopausal EC patients’ progression by integrated analyses. This finding may improve targeted therapy for EC patients.

A ten-gene methylation signature as a novel biomarker for improving prediction of prognosis and indicating gene targets in endometrial cancer

Endometrial cancer (EC) is a common female reproductive tumor worldwide. Nonetheless, the pathogenesis of EC still remains ambiguous and associated epigenetic mechanism still to be explored. The goal of this study is to investigate whether gene methylation signature is associated with overall survival (OS) for EC patients. In this study, a 10-gene methylation risk model was built and the OS in high- and low-risk groups was significant different. The area under the ROC curve (AUC) of this model was 0.856 at 5 years survival. The nomogram could accurately predict the OS in EC patients, with concordance index and AUC at 5 year survival reached 0.796 and 0.792, respectively. Furthermore, we verified the nomogram with 24 patients in our center and the Kaplan-Meier survival curve also proved to be significantly different (p < 0.01). WGCNA revealed a key gene group for the model and further bioinformatics analysis indicated 6 genes as the hub genes in the module. Knockdown of MMP12 inhibited the proliferation, invasion and metastasis of EC cells. After all, a methylation signature and a nomogram based on this signature were constructed, and they could both predict survival in patients with EC. Moreover, WGCNA model identified MMP12 as a potential target for the treatment of EC.

B3GNT3 acts as a carcinogenic factor in endometrial cancer via facilitating cell growth, invasion and migration through regulating RhoA/RAC1 pathway-associated markers.

Aberrant expression of beta-1,3-N-acetylglucosaminyltransferase-3 (B3GNT3) has been frequently clarified in various cancers, however, its role in endometrial cancer (EC) has not been assessed in detail. This study aimed to investigate the biological role of B3GNT3 in EC and simply explored the detailed mechanism. The EC RNA-Seq dataset from TCGA database was applied to evaluate the expression of B3GNT3 and assess its role on prognostic value. HEC-1-A and KLE cell lines of EC were used to perform loss- and gain-of-function B3GNT3 assays respectively. Quantitative real-time PCR (qRT-PCR) and western blot were used to measure the mRNA and protein levels of indicated molecules respectively. Cell counting kit-8, clone formation tests, and Transwell assay served to determine the changes of proliferative, invasive and migratory abilities of EC cells after altering the expression of B3GNT3. B3GNT3 was found to be highly expressed in EC tissues compared to normal tissues according to the online public databases, which confirmed by the following qRT-PCR in 3 EC cell lines. Besides, high B3GNT3 expression presented a worse overall survival in EC patients as compared with low B3GNT3 expression group. Furthermore, functional experiments in vitro indicated that B3GNT3 could facilitate the cell growth, invasion and migration. Moreover, we found that downregulation of B3GNT3 significantly reduced the expression level of GTP-RhoA and GTP-RAC1, whereas upregulation of B3GNT3 presented the opposite results. The results of current study demonstrate that B3GNT3 acts as an oncogene that promotes EC cells growth, invasion and migration possibly through regulating the RhoA/RAC1 signaling pathway-related markers, suggesting that B3GNT3 may be a candidate biomarker for EC therapeutic intervention.

Tribbles Pseudokinase 3 Contributes to Cancer Stemness of Endometrial Cancer Cells by Regulating β-Catenin Expression.

Simple SummaryEndometrial cancer (EC) is the second most common female malignancy worldwide, but the pathogenesis is not fully understood. Tribbles pseudokinase 3 (TRIB3) is a kind of scaffold protein that may regulate multiple cellular processes by organizing binding partner proteins involving signaling transduction pathways. The goal of this study is to investigate if TRIB3 is involved in the malignant features of EC. Our data demonstrate that TRIB3 positively regulates the cancer stem-cell activity and in vivo tumorigenicity of EC cells by modulating β-catenin signaling through directly interacting with the ELF4 transcription factor. Our results could lead to new insight for developing a novel therapeutic strategy for EC by targeting TRIB3.Endometrial cancer (EC) is the second most common gynecological malignancy worldwide. Tribbles pseudokinase 3 (TRIB3) is a scaffolding protein that regulates intracellular signal transduction, and its role in tumor development is controversial. Here, we investigated the biological function of TRIB3 in EC. We found that the messenger RNA (mRNA) expression level of TRIB3 was significantly and positively correlated with shorter overall survival of EC patients in The Cancer Genome Atlas database. The protein expression of TRIB3 was found to be significantly increased in EC cancer stem cells (CSCs) enriched by tumorsphere cultivation. Knockdown of TRIB3 in EC cells suppressed tumorsphere formation, the expression of cancer stemness genes, and the in vivo tumorigenesis. The expression of β-catenin at both the protein and the mRNA levels was downregulated upon TRIB3 silencing. TRIB3 was found to interact with E74 Like ETS transcription factor 4 (ELF4) in the nucleus and bound to ELF4 consensus sites within the catenin beta 1 (CTNNB1) promoter in EC cell lines. These data indicated that TRIB3 may regulate CTNNB1 transcription by enhancing the recruitment of ELF4 to the CTNNB1 promoter. In conclusion, our results suggest that TRIB3 plays an oncogenic role in EC and positively regulates the self-renewal and tumorigenicity of EC-CSCs. Targeting TRIB3 is considered as a potential therapeutic strategy in future EC therapy.

Ubiquitin C-Terminal Hydrolase L5 (UCHL5) Accelerates the Growth of Endometrial Cancer via Activating the Wnt/β-Catenin Signaling Pathway.

Endometrial cancer (EC) is the most prevalent gynecological malignancy with high mortality. Chemotherapy plays a pivotal role both in an adjuvant setting and in exclusive treatment. However, current pharmacotherapies are limited and not ideal for improving the overall survival of EC patients. Thus, identification of the underlying molecular mechanisms responsible for initiation and progression of EC is imperative for developing novel therapeutic strategies. Ubiquitin C-terminal hydrolase L5 (UCHL5) has been found to aggravate tumor growth and metastasis in several different types of tumor models such as esophageal squamous cell carcinoma, hepatocellular carcinoma, and epithelial ovarian cancer. However, whether UCHL5 influences the growth of EC has not been elucidated. To expose the role of UCHL5 on EC, bioinformatics analysis was conducted, and it hinted that UCHL5 was overexpressed in EC tissues and associated with lower overall survival. Consistently, the overexpression of UCHL5 in EC tissues and cell lines was further confirmed by western blot (WB) and polymerase chain reaction (PCR) compared with non-tumor control. Lentivirus vectors carrying UCHL5 shRNA or CD sequences were used to reduce or overexpress the UCHL5 gene, respectively. Cell proliferation and cycle were facilitated, and cell apoptosis was decreased when the UCHL5 gene was overexpressed in EC cell lines. These results were opposite in UCHL5 knockdown EC cells. Additionally, the expression of β-catenin is positively related to UCHL5 levels and the tumorigenic effects of UCHL5 overexpression were reversed by the Wnt/β-catenin pathway inhibitor XAV939. Thus, Wnt/β-catenin pathway activation may be a partial mechanism responsible for the promoting effects of UCHL5 on EC growth. In conclusion, UCHL5 accelerated the growth of EC via the Wnt/β-catenin pathway and was expected to be an attractive target for EC treatment.

Tissue Infiltrating Immune Cells as Prognostic Biomarkers in Endometrial Cancer: A Meta-Analysis.

Background The association between tumour-infiltrating immune cells and the prognosis of endometrial cancer (EC) is controversial due to the smaller sample sizes and limited statistical power of the extant studies. We carried out a meta-analysis of the relationship between tumour-infiltrating immune cells and EC survival outcomes. Methods A literature search in multiple databases was carried out up to December 2019. Pooled hazard ratio (HRs) and 95% confidence intervals (CIs) were calculated by the Z-test to assess the association between infiltrating immune cells and overall survival (OS), progression-free survival (PFS), relapse-free survival (RFS), disease-specific survival (DSS), and disease-free survival (DFS). A subgroup analysis was performed based on the localisation of immune cells in tumour parenchyma or stroma, immune markers, and the International Federation of Gynecology and Obstetrics stage. Heterogeneity and publication bias between studies were evaluated by Cochran's Q-test and Egger regression test, respectively. Results Seventeen studies were included in the analysis. The pooled HR of OS, PFS, DSS, and DFS indicated that a high CD8+ T cell density was associated with a favorable prognosis in EC patients. A significant relationship was found between a high density of CD45RO+ T cells and a favorable OS in EC patients, but the FoxP3+ T cell density was not associated with either OS or RFS. A high TAM density was associated with a worse PFS. However, a sensitivity analysis indicated that the findings of PFS and DSS in CD8+ T cell and PFS in TAM were not robust results. Conclusion This is the first meta-analysis of the relationship between tumour-infiltrating immune cells and the prognosis of EC. High CD8+ and CD45RO+ T cell densities in tumours were associated with favorable outcomes in EC patients.

Prognostic Potential of Alternative Splicing Markers in Endometrial Cancer

Alternative splicing (AS), an important post-transcriptional regulatory mechanism that regulates the translation of mRNA isoforms and generates protein diversity, has been widely demonstrated to be associated with oncogenic processes. In this study, we systematically analyzed genome-wide AS patterns to explore the prognostic implications of AS in endometrial cancer (EC). A total of 2,324 AS events were identified as being associated with the overall survival of EC patients, and eleven of these events were further selected using a random forest algorithm. With the implementation of a generalized, boosted regression model, a prognostic AS model that aggregated these eleven markers was ultimately established with high performance for risk stratification in EC patients. Functional analysis of these eleven AS markers revealed various potential signaling pathways implicated in the progression of EC. Splicing network analysis demonstrated the notable correlation between the expression of splicing factors and AS markers in EC and further determined eight candidate splicing factors that could be therapeutic targets for EC. Taken together, the results of this study present the utility of AS profiling in identifying biomarkers for the prognosis of EC and provide comprehensive insight into the molecular mechanisms involved in EC processes.

A four-miRNA signature as a novel biomarker for predicting survival in endometrial cancer

BackgroundThe microRNAs (miRNAs) have been validated as prognostic markers in many cancers. The aim of this study was to identify new miRNA prognostic biomarkers in endometrial cancer (EC) and to develop an expression-based miRNA signature to provide survival risk prediction for EC patients. MethodsFrom TCGA database, the miRNA datasets of EC and clinical information were downloaded in April 2018. Using univariate and multivariate Cox regression analyses identify prognostic factors. Using area under the curve (AUC) of receiver operating characteristic (ROC) curve assess the sensitivity and specificity of prognostic model. Results530 patients were randomly divided into training set and testing set. Among 561 differentially expressed miRNAs, 4 miRNAs (miR-4758, miR-876, miR-142, miR-190b) were demonstrated to be predictive biomarkers of overall survival (OS) for EC patients in training set. Based on the risk score of 4-miRNA model, patients in the training set were divided into high-risk and low-risk groups with significantly different OS. This 4-miRNA model was validated in testing and entire set. The AUC for the ROC curves in the entire set was 0.704. Meanwhile, multivariate Cox regression combined with other traditional clinical parameters indicated that the 4-miRNA model can be used as an independent OS prognostic factor. Functional enrichment analysis revealed that these miRNAs are involved in biological processes and pathways that are closely related to cancer. ConclusionA robust 4-miRNA signature as an independent prognostic factor for OS in EC patients was established.

Effect of metformin use on the risk and prognosis of endometrial cancer: a systematic review and meta-analysis

BackgroundPrevious studies have suggested that metformin may be useful for preventing and treating endometrial cancer (EC), while the results have been inconsistent. This systematic review and meta-analysis aimed to investigate the association between metformin use and risk and prognosis of patients with EC.MethodsPubMed, Embase, and the Cochrane Library databases were searched for observational studies evaluating the effect of metformin on EC prevention or treatment. The odds ratio (OR) was used for analyzing risks, and the hazard ratio (HR) was used for analyzing survival outcomes. A random-effects model was used for data analysis.ResultsSeven studies reported data on EC risk. The pooled results suggested that metformin was not significantly associated with a lower risk of EC [OR = 1.05, 95% confidence interval (CI) 0.82–1.35, P = 0.70]. For patients with diabetes, metformin showed no advantage in reducing the EC risk compared with other interventions (OR = 0.99, 95% CI 0.78–1.26, P = 0.95). Further, seven studies were included for survival analysis. The pooled data showed that metformin could significantly improve the overall survival of patients with EC (HR = 0.61, 95% CI 0.48–0.77, P < 0.05) and reduce the risk of EC recurrence (OR = 0.50, 95% CI 0.28–0.92, P < 0.05) Finally, we noted metformin was associated with significantly improving the overall survival of EC patients among diabetes (HR = 0.47; 95%CI 0.33–0.67, P < 0.05).ConclusionsThis meta-analysis did not prove that metformin was beneficial for preventing EC. However, metformin could prolong the overall survival of patients with EC and reduce their risk of cancer relapse.

The prognostic value of D-dimer levels in endometrial cancer patients treated with intensity-modulated radiation therapy.

Explain the important role of plasma D-dimer in cancers. Plasma D-dimer is increased in various tumors. However, the predictive value of plasma D-dimer is unclear. This study is aimed to evaluate the prognostic value of the D-dimer level in patients managed with intensity-modulated radiation for endometrial cancer. The D-dimer levels of forty patients with endometrial cancer were assessed before (D1) and after (D2) intensity-modulated radiation therapy (IMRT), respectively. The D-dimer level changes (ΔD) were defined as D2 minus D1. Cox regression and log-rank tests were used to evaluate the D-dimer levels in relation to progression free survival (PFS) and overall survival (OS). The OS and PFS of patients with a low D1 were significantly longer than those with a high D1 (P< 0.001, P< 0.001). We saw the similar correlation between D2, PFS and OS (P< 0.001, P< 0.001). Multivariate survival analyses showed that D-dimer was independently associated with OS and PFS in patients with endometrial cancer. The ΔD level was not related to the OS and PFS in endometrial cancer patients. The levels of D-dimer may be considered as an important predictor of PFS and OS in endometrial cancer patients treated with IMRT.

Catheter Angiography, MR Angiography, and MR Perfusion in Posterior Reversible Encephalopathy Syndrome

The cause of posterior reversible encephalopathy syndrome (PRES) is unknown. Two primary hypotheses exist: 1) hypertension exceeding auto-regulatory limits leading to forced hyper-perfusion and 2) vasoconstriction and hypo-perfusion leading to ischemia with resultant edema. The purpose of this study was to evaluate the catheter angiography (CA), MR angiography (MRA), and MR perfusion (MRP) features in PRES in order to render further insight into its mechanism of origin. In 47 patients with PRES, 9 CAs and 43 MRAs were evaluated for evidence of vasculopathy (vasoconstriction and vasodilation), and 15 MRP studies were evaluated for altered relative cerebral blood volume (rCBV) in PRES lesions and regions. Visualization of vessels on MRA and toxicity blood pressures were compared with the extent of hemispheric vasogenic edema. Vasculopathy was present in 8 of 9 patients on CA (direct correlation to MRA in 3/6 patients). At MRA, moderate to severe vessel irregularity consistent with vasoconstriction and vasodilation was present in 30 of 43 patients and vessel pruning or irregularity in 7 patients, with follow-up MRA demonstrating reversal of vasoconstriction or vasodilation in 9 of 11 patients. Vasogenic edema was less in patients with hypertension compared with patients who were normotensive. Preserved normal length of the posterior cerebral artery (PCA) was commonly seen in patients with severe hypertension despite diffuse or focal vasoconstriction or vasodilation. In these patients, lengthier visualization of the distal PCA correlated with a lower grade of hemispheric edema (P = .002). Cortical rCBV was significantly reduced in 51 of 59 PRES lesions and regions compared with a healthy reference cortex (average 61% of reference cortex) with mild decrease in the remainder. Vasculopathy was a common finding on CA and MRA in our patients with PRES, and MRP demonstrated reduced cortical rCBV in PRES lesions. Vasogenic edema was reduced in patients with hypertension, and superior distal PCA visualization correlated with reduced hemispheric edema in patients with PRES and severe hypertension.