Survival Of Endometrial Cancer Patients Research Articles

Dostarlimab A new hope for endometrial cancer patients in Pakistan

Endometrial cancer (EC) is the most common gynaecological cancer in Pakistan, with an estimated incidence of 7.4 per 100,000 women [1]. It is a disease where cancer cells grow in the lining of the uterus (endometrium). EC can be classified into two types based on the genetic features of the cancer cells: mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H), and mismatch repair proficient (pMMR) or microsatellite stable (MSS). The former type accounts for about 20-30% of EC cases and has a worse prognosis than the latter [2]. Dostarlimab is a monoclonal antibody that blocks a protein called PD-1 on immune cells. The immune system is often restrained by PD-1, which stops it from targeting healthy cells. However, some cancer cells can exploit this mechanism by producing proteins (PD-L1 and PD-L2) that bind to PD-1 and switches off the immune response. By blocking PD-1, Dostarlimab restores the immune system’s ability to recognise and kill cancer cells [3]. Dostarlimab has been approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of adults with dMMR/MSI-H recurrent or advanced EC that has progressed on or following prior treatment with a platinum-containing regimen [4,5]. Clinical studies have shown positive results for Dostarlimab in this patient population. In the GARNET trial, Dostarlimab achieved an objective response rate (ORR) of 43.5%, meaning that 43.5% of patients had their tumours shrink or disappear after treatment [3]. The median duration of response (DOR) was not reached, indicating that most responses persisted [8]. The most common side effects of Dostarlimab were fatigue, nausea, diarrhoea, anaemia, and constipation [5]. Dostarlimab offers new hope for endometrial cancer patients in Pakistan who have limited treatment options and poor outcomes. It is a targeted therapy that harnesses the power of the immune system to fight cancer. It is also a convenient and well-tolerated treatment that can be administered every 3 or 6 weeks as an intravenous infusion [2,3]. Dostarlimab is not yet available in Pakistan, but efforts are underway to bring it to the country as soon as possible. Dostarlimab has the potential to improve the quality of life and survival of endometrial cancer patients in Pakistan who have dMMR/MSI-H tumours.

The inflammatory markers combined with CA125 may predict postoperative survival in endometrial cancer

Background Endometrial cancer (EC) has a high latency, making prognosis difficult to predict. Cancer antigen 125 (CA125) is not specific as a tumour marker for EC; however, complete blood count (CBC) inflammatory markers are associated with prognosis in various malignancies. Thus, this study investigated the value of CBC inflammatory markers combined with CA125 levels in predicting the prognosis of patients with EC. Methods In this study, 517 patients with EC were recruited between January 2015 and January 2022, and clinical characteristics, CBC inflammatory markers, and CA125 levels were assessed. Differences in each index at different EC stages and the correlation between the index and EC stage were analysed, and the influence of the index on EC prognosis was evaluated. Results Platelet distribution width (PDW) levels were significantly lower in patients with advanced EC than in those with early EC, whereas the systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and CA125 levels were significantly higher in patients with advanced EC (all P < 0.05). ROC curve and multivariate logistic regression analyses indicated that decreased PDW and increased CA125 levels were independent risk factors for EC staging progression. In addition, multivariate Cox regression analysis showed that the combination of low PDW and high CA125 (PDW + CA125 = 2) was an independent prognostic factor of survival in EC patients. Kaplan-Meier survival analysis indicated that patients with low PDW and high CA125 had worse overall survival. Conclusions The PDW and CA125 score may be an independent prognostic factor for postoperative overall survival in patients with EC and a useful marker for predicting the prognosis of these patients.

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.

The Impact of Waiting Time-to-Surgery on Survival in Endometrial Cancer Patients.

Endometrial cancer (EC) is the most common gynecological cancer in developed countries and a standard treatment of surgery should be performed as expediently as possible. Delay time to surgery and survival was debated. The aim of this investigation was to evaluate the effect of time-interval between diagnosis and surgery (TDS) in EC patients with regards to prognosis and mortality rates. This retrospective study was conducted between January 2009 and May 2021 at Bhumibol Adulyadej Hospital, Thailand. Subjects were EC cases who underwent primary surgery during the study period. Cases with partial treatment were disqualified from the study. Subjects who underwent surgery before and after 6 weeks were classified as early and delayed surgery groups. Baseline and clinical characteristics were collected and analyzed. During the study period, 419 EC cases were recruited. The mean age of participants was 56.8 years. Two-thirds (338/491) of subjects were menopausal. Endometrioid histology (406/491) was the most common histology subtype. Five years disease free survival (DFS) of early and delayed surgery groups were comparable at a percentage of 82.5 and 83.0, respectively. Among advanced stage and non-endometrioid EC cases, the delayed surgery group had significantly shorter DFS than the early group. Advanced stage, high grade and positive lympho-vascular space invasion (LVSI) were independent factors for poor DFS. Predictive factors for mortality were advanced stage and tumor recurrence. The TDS was not a prognostic factor for disease recurrence or overall mortality. Time to surgery equal to or more than 6 weeks gave worse prognosis for DFS among advanced stage or non-endometrioid histology EC.

The impact of metformin on survival in diabetic endometrial cancer patients: a retrospective population-based analysis

PurposeThe aim of our study was to assess overall survival and cancer-specific survival in endometrial cancer patients with type 2 diabetes mellitus (T2DM) using metformin.MethodsPatients with endometrial cancer and T2DM during 2000–2012 period were identified from the Lithuanian Cancer Registry and the National Health Insurance Fund database. Cancer-specific and overall survival were primary outcomes.ResultsIn our study we included 6287 women with endometrial cancer out of whom 664 were diagnosed with T2DM (598 metformin users and 66 never users). During follow-up (mean follow-up time was 8.97 years), no differences in risk of endometrial cancer specific mortality was observed in diabetic patients treated with metformin (Hazard Ratio (HR) 0.87, 95% Confidence Interval (CI) 0.70–1.07). Overall mortality in the diabetic metformin ever users’ group was significantly higher compared with the non-diabetic endometrial cancer women (HR 1.17, 95% CI 1.03–1.32) and in the group of metformin never users with T2DM (HR 1.42, 95% CI 1.07–1.87).ConclusionOur study results suggest no beneficial impact on overall and cancer-specific survival in endometrial cancer patients who were treated with metformin as part of their diabetes treatment.

Efficacy of transumbilical laparoendoscopic single-site surgery versus multi-port laparoscopic surgery for endometrial cancer: a retrospective comparison study.

Although single-port laparoscopy surgery has been evaluated for several years, it has not been widely adopted by gynecologic oncologists. The objective was to compare the perioperative outcomes and survival of endometrial cancer (EC) patients undergoing transumbilical laparoendoscopic single-site surgery (TU-LESS) with multi-port laparoscopic surgery (MLS). This is a retrospective comparative monocentric study including patients treated between December 2017 and October 2021. The perioperative outcomes and survival of EC patients who had surgery via TU-LESS or MLS were compared, by propensity matching. A total of 156 patients were included (TU-LESS vs. MLS: 78 vs. 78). The conversion rate of TU-LESS and MLS was 5.13% and 2.56%, respectively (P=0.681). The operation time was comparable between the two groups [207.5min (180-251) vs. 197.5min (168.8-225), P=0.095]. There was no significant difference between the two groups in exhaustion time, perioperative complications, or postoperative complications. While, the TU-LESS group had a shorter out-of-bed activity time [36 hours (24-48) vs. 48 hours (48-72), P<0.001] and a lower visual analog pain scale 36 hours after surgery [1 (1-2) vs. 2 (1-2), P<0.001] than the MLS group. The length of hospital stay was similar in the two groups [5(4-6) vs. 5(4-5), P=0.599]. Following surgery, 38.5% of the TU-LESS patients and 41% of the MLS patients got adjuvant therapy (P=0.744). The median follow-up time for TU-LESS and MLS cohorts was 45 months (range: 20-66) and 43 months (range: 18-66), respectively. One TU-LESS patient and one MLS patient died following recurrence. The 4-year overall survival was similar in both groups (98.3% vs. 98.5%, P=0.875). TU-LESS is a feasible and safe option with comparable perioperative outcomes and survival of MLS in endometrial cancer. With the growing acceptance of sentinel lymph node biopsy, TU-LESS of endometrial cancer may be a viable option for patients and surgeons.

Non-SMC Condensin I Complex Subunit G Promotes the Proliferation, Invasion and Homologous Recombination Repair of Endometrial Cancer Through PI3K/AKT Signaling Pathway

This study aimed to investigate the role of Non-SMC condensin I complex subunit G (NCAPG) in endometrial cancer (EC) progression and prognosis. The researchers utilized various techniques, including analysis of The Cancer Genome Atlas (TCGA) database, immunohistochemistry, qRT-PCR, Western blotting, and functional assays to assess the impact of NCAPG on EC cells. The TCGA analysis revealed that NCAPG was significantly associated with overall survival and disease-free survival in EC patients. Immunohistochemistry analysis further confirmed a positive correlation between NCAPG expression, histological grade, and myometrial invasion in EC tissues. In vitro experiments demonstrated that NCAPG promoted EC cell proliferation, invasion, and influenced the G1/S cell cycle transition. Additionally, NCAPG was found to regulate the expression of FANCD2 and RAD51 in the homologous recombination repair pathway, and its knockdown sensitized EC cells to poly (ADP-ribose) polymerase inhibitors. The study also revealed the involvement of the PI3K/AKT signaling pathway in mediating the effects of NCAPG on EC cells’ proliferation, invasion, and homologous recombination repair. In conclusion, NCAPG acts as an oncogene in EC, driving proliferation, invasion, and homologous recombination repair through the PI3K/AKT pathway. NCAPG expression correlates with EC prognosis, revealing its significance as a therapeutic target for advanced cases, illuminating EC progression mechanisms.

Accelerated Failure Time Models with Applications to Endometrial Cancer Survival Data

The objective of this study is to determine the significant predictors of endometrial cancer using accelerated failure time models (AFTM). We have demonstrated the applications of AFTM viz. Exponential, Weibull, Log-normal, Log-logistic, Gompertz, Gamma and Generalized Gamma AFTM, as an alternative of Cox proportional hazard model. Data for the analysis was collected from Acharya Harihar Post Graduate Institute of Cancer (AHPGIC), Cuttack, Odisha during the period 2016–20. Based on the lowest Akaike Information Criterion (AIC) and Bayesian Information Criterion (BIC) value, the Weibull AFTM has been chosen as the best fitted AFT model. The predictors such as age, comorbidity, tumor size, isolated para-aortic and adnexa have been found as significant predictors (p-value &lt; 0.05) to explain the survival of endometrial cancer patients. Hence, by optimizing different treatments, based on such prognostic factors plays an important role in managing endometrial cancer at an early stage.

PIK3CA mutations and their impact on survival outcomes of patients with endometrial cancer: A systematic review and meta-analysis.

Several studies have highlighted the frequent alterations of the PI3K pathway in endometrial cancer leading to increased signaling activation with potential for targeted treatment. The objective of this meta-study was to evaluate how PIK3CA exon 9/20 mutations affect survival in endometrial cancer patients, based on available literature. Topic-based search strategies were applied to databases including CENTRAL, MEDLINE, Embase, Web of Science and COSMIC. All studies assessing the impact of mutations in exon 9 and exon 20 of PIK3CA on survival rates of endometrial cancer patients were selected for inclusion. Statistical meta-analysis was performed with the 'meta' package in RStudio. Overall, 7 of 612 screened articles were included in the present study, comprising 1098 women with endometrial cancer. Meta-analysis revealed a tendency of impaired survival for patients with PIK3CA exon 9 and/or exon 20 mutations (RR 1.28; 95% CI 0.84, 1.94; p = 0.25). This tendency was consistent in subgroup analyses stratified by histologic type or -grade, with the most prominent effect in low-grade endometrial cancers (RR 2.04; 95% CI 0.90, 4.62; p = 0.09). In summary, these results suggest that PIK3CA mutations negatively influence survival outcomes of patients with endometrial cancer, including those with low-grade tumors.

Integrated multi-omics analyses and functional validation reveal TTK as a novel EMT activator for endometrial cancer

BackgroundCancer-testis antigens (CTAs) are often expressed in tumor and testicular tissues but not in other normal tissues. To date, there has been no comprehensive study of the expression and clinical significance of CTA genes associated with endometrial cancer (EC) development. Additionally, the clinical relevance, biological role, and molecular mechanisms of the CTA gene TTK protein kinase (TTK) in EC are yet to be fully understood.MethodsUsing bioinformatics methods, we comprehensively investigated the genomic, transcriptomic, and epigenetic changes associated with aberrant TTK overexpression in EC samples from the TCGA database. We further investigated the mechanisms of the lower survival associated with TTK dysregulation using single-cell data of EC samples from the GEO database. Cell functional assays were used to confirm the biological roles of TTK in EC cells.ResultsWe identified 80 CTA genes that were more abundant in EC than in normal tissues, and high expression of TTK was significantly linked with lower survival in EC patients. Furthermore, ROC analysis revealed that TTK could accurately distinguish stage I EC tissues from benign endometrial samples, suggesting that TTK has the potential to be a biomarker for early EC detection. We found TTK overexpression was more prevalent in EC patients with high-grade, advanced tumors, serous carcinoma, and TP53 alterations. Furthermore, in EC tissue, TTK expression showed a strong positive correlation with EMT-related genes. With single-cell transcriptome data, we identified a proliferative cell subpopulation with high expression of TTK and known epithelial–mesenchymal transition (EMT)-related genes and transcription factors. When proliferative cells were grouped according to TTK expression levels, the overexpressed genes in the TTKhigh group were shown to be functionally involved in the control of chemoresistance. Utilizing shRNA to repress TTK expression in EC cells resulted in substantial decreases in cell proliferation, invasion, EMT, and chemoresistance. Further research identified microRNA-21 (miR-21) as a key downstream regulator of TTK-induced EMT and chemoresistance. Finally, the TTK inhibitor AZ3146 was effective in reducing EC cell growth and invasion and enhancing the apoptosis of EC cells generated by paclitaxel.ConclusionOur findings establish the clinical significance of TTK as a new biomarker for EC and an as-yet-unknown carcinogenic function. This present study proposes that the therapeutic targeting of TTK might provide a viable approach for the treatment of EC.

Menopausal Status Contributes to Overall Survival in Endometrial Cancer Patients.

Endometrial cancer is the most common female genital tract malignancy in developed countries that occurs predominantly in postmenopausal women. The primary objective of our research was to investigate whether menopause status together with selected conventional prognostic indicators may contribute to overall (all-cause) survival in endometrial cancer patients. For this purpose, we applied the Cox proportional hazards regression model. Patients in advanced FIGO stage showed a relatively poor survival rate. The time since last menstruation and postoperative FSH concentration were identified as unfavorable prognostic factors in our model. Additionally, age at diagnosis, BMI value, adjuvant treatment (brachytherapy), and parity showed no impact on survival. To our knowledge, this is the first study to report a prognostic model for endometrial cancer including exact time from last menstruation as one of the prognostic variables. Due to the fact that there are no stratifying systems to reliably predict survival in patients with endometrial cancer, there is a strong need to revise and update existing models using complementary prognostic indicators. Collection of precise data on various risk factors may contribute to increased accuracy of artificial intelligence algorithms in order to personalize cancer care in the near future.

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.

Hysterectomy or/and lymphadenectomy for the survival of patients with primary endometrial cancer: a cohort study using the SEER database

ABSTRACT In order to provide a clinical reference for endometrial cancer treatment, this retrospective cohort study aimed to assess and compare the survival of endometrial cancer patients undergoing hysterectomy versus lymphadenectomy and hysterectomy combined with lymphadenectomy. The Surveillance, Epidemiology, and End Results (SEER) database provided data on patients with primary endometrial cancer enrolled between 1975 and 2016. The longest follow-up time was ten years, and the median follow-up time was 51.00 months. The outcomes were overall survival (OS) and cancer-specificsurvival (CSS). COX models were constructed to assess the relationship between the three surgical methods and OS or CSS. Subgroup analyses were conducted based on American Joint Committee on Cancer (AJCC) stage and menopausal status. Totally 134,597 patients were included. In stage IV, the lymphadenectomy group had significantly worse OS than the hysterectomy group (HR = 1.330, 95%CI = 1.101–1.606). The hysterectomy combined with lymphadenectomy group had similar OS to the hysterectomy group (HR = 1.183, 95%CI = 0.996–1.405). Regarding CSS, no significant differences were found between the hysterectomy and lymphadenectomy groups (HR = 1.267, 95%CI = 0.996–1.610), and between the hysterectomy and hysterectomy combined with lymphadenectomy groups (HR = 1.186, 95%CI = 0.953–1.476) in stage IV. For postmenopausal women, lymphadenectomy (HR = 1.655, 95%CI = 1.495–1.831) and hysterectomy combined with lymphadenectomy (HR = 1.129, 95%CI = 1.038–1.228) were associated with significantly decreased OSthan hysterectomy. For CSS among postmenopausal women, significant declines inCSS were found in the lymphadenectomy (HR = 2.264, 95%CI = 1.957–2.619) and hysterectomy combined with lymphadenectomy (HR = 1.419, 95%CI = 1.260–1.599) groups versus the hysterectomy group. Hysterectomy may serve as a decision-making reference for clinicians in treating patients in stage IV or after menopause, combined with clinical experience and patients’ wishes.

Decreased expression of miR-23b is associated with poor survival of endometrial cancer patients

Endometrial cancer (EC) is one of the most common types of cancer of the female reproductive system. EC is classified into two types (EC1 and EC2). MiRNAs are single-stranded RNA molecules that regulate gene expression posttranscriptionally. They have aberrant expression profiles in cancer, including EC. This study aimed to assess the level of expression of a panel of 16 miRNAs in both types of EC and healthy endometrium (HE). A total of 45 patients were enrolled into the study, 18 patients diagnosed with EC1, 12 diagnosed with EC2, and 15 HE controls. Tumor tissues or healthy endometrial tissues were dissected from archival formalin-fixed paraffin-embedded (FFPE) using laser capture microdissection (LCM). RNA was isolated from collected material and the expression of selected miRNAs was determined using the real-time qPCR. We found that miR-23b, miR-125b-5p, miR-199a-3p, miR-221-3p, and miR-451a were downregulated in EC in comparison to HE. Moreover, the expression of miR-34a-5p and miR-146-5p was higher in EC1 compared to EC2. Analysis of The Cancer Genome Atlas (TCGA) database confirmed decreased levels of miR-23b, miR-125b-5p, and miR-199a-3p in EC. Decreased miR-23b expression was associated with worse survival of EC patients.

Disparities in the survival of endometrial cancer patients in a public healthcare system: A population-based cohort study

ObjectiveSocial determinants of health (SDH) have been shown to correlate with adverse cancer outcomes. It is unclear if their impact goes beyond behavioral risk or healthcare access. We aimed to evaluate the association of SDH with endometrial cancer outcomes in a public healthcare system. MethodsA retrospective cohort study of endometrial cancer patients diagnosed between 2009 and 2017 in Ontario, Canada. Clinical and sociodemographic variables were extracted from administrative databases. Validated multifactorial marginalization scores for domains of material deprivation, residential instability and ethnic concentration were used. Associations between marginalization and survival were evaluated using log-rank testing and Cox proportional hazards regression. Results20228 women with endometrial cancer were identified. Fewer patients in marginalized communities presented with early disease (70% vs. 76%, p < 0.001) and received surgery (89% vs. 93%, p < 0.001). Overall survival was shorter among marginalized patients (p < 0.001). On multivariable analysis adjusted for patient and disease factors, overall marginalization (HR = 1.22, 95% CI 1.03–1.08), material deprivation (HR = 1.22, 95% CI 1.10–1.35) and residential instability (HR = 1.32, 95% CI 1.19–1.46) were associated with increased risk of death (p < 0.001). ConclusionsSocioeconomic marginalization is associated with an increased risk of death in endometrial cancer patients. Targetable events in the cancer care pathway should be identified to improve health equity. FundingThis study was supported by a grant (#RD-196) from the Hamilton Health Sciences Juravinski Hospital and Cancer Center Foundation.

The correlation between APOE expression and the clinical characteristics and prognosis of patients with endometrial cancer.

To analyze the expression of apolipoprotein E (APOE) in endometrial cancer and its influence on the long-term prognostic survival of endometrial cancer patients. The specimens of tumor tissues and adjacent normal tissues from 96 endometrial cancer patients from January 2013 to December 2015 were included in this study. Immunohistochemistry was used to measure the expression of APOE in tumor tissues and adjacent normal tissues. Statistical analysis was used to examine the correlation between APOE expression and the clinicopathological characteristics and survival of patients. Kaplan–Meier survival curve was drawn to study the effects of APOE on the prognosis of patients. The positive rate of APOE in endometrial cancer tissue was higher than that in adjacent normal tissues. The expression level of APOE in endometrial cancer was correlated with histological grade, lymph node metastasis, and FIGO stage (P < .05). Lymph node metastasis and APOE were independent risk factors affecting the prognosis and survival of patients (P < .05). The results of Kaplan–Meier survival analysis showed that the survival time of APOE high expression group was shorter than that of low APOE expression. APOE is overexpressed in endometrial cancer tissues, and its expression level can provide important information for clinical diagnosis and treatment.

Upregulated keratin 15 links to the occurrence of lymphovascular invasion, stromal cervical invasion as well as unfavorable survival profile in endometrial cancer patients.

Keratin 15 (KRT15) overexpression links with tumor initiation, metastasis, and poor survival in several solid carcinomas. While its clinical relevance is scarcely reported in endometrial cancer (EC). Therefore, the current study aimed to investigate the abnormal expression of KRT15 and its correlation with clinical characteristics, survival in EC patients.Totally, 135 surgical EC patients were enrolled. KRT15 protein expression in formalin-fixed and paraffin-embedded tumor and adjuvant tissues was detected by immunohistochemical staining; meanwhile, KRT15 mRNA expression in fresh-frozen tumor and adjacent tissues was detected by reverse transcription-quantitative polymerase chain reaction.KRT15 protein and mRNA expressions were higher in tumor tissue compared with adjacent tissue (both P < .001). Elevated KRT15 protein expression was correlated with the occurrence of lymphovascular invasion (P = .010) and more advanced International Federation of Gynecology and Obstetrics stage (P = .018); meanwhile, elevated KRT15 mRNA expression was linked with more advanced International Federation of Gynecology and Obstetrics stage (P = .038) and marginally associated with the occurrence of stromal cervical invasion (P = .052). Besides, KRT15 protein and mRNA expressions were not correlated with other clinical features (all P > .05). KRT15 protein high was marginally correlated with poor accumulating disease-free survival (DFS) (P = .091) and overall survival (OS) (P = .059); meanwhile, the correlation of KRT15 mRNA expression with accumulating DFS (P = .212) and OS (P = .092) was even weaker. However, multivariate Cox’s regressions showed that tumor KRT15 protein (high vs low) was independently correlated with poor DFS (P = .045) and OS (P = .043).KRT15 is abnormally increased in EC tissue, meanwhile, its upregulation links to the occurrence of lymphovascular invasion, stromal cervical invasion, and poor prognosis in EC patients.

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.