scholarly journals CD133 Expression in the Nucleus Is Associated with Endometrial Carcinoma Staging and Tumor Angioinvasion

2021 ◽  
Vol 10 (10) ◽  
pp. 2144
Author(s):  
Milosz Pietrus ◽  
Kazimierz Pitynski ◽  
Marcin Waligora ◽  
Katarzyna Milian-Ciesielska ◽  
Monika Bialon ◽  
...  

Background: (1) Endometrial cancer is one of the most common cancers affecting women, with a growing incidence. To better understand the different behaviors associated with endometrial cancer, it is necessary to understand the changes that occur at a molecular level. CD133 is one of the factors that regulate tumor progression, which is primarily known as the transmembrane glycoprotein associated with tumor progression or cancer stem cells. The aim of our study was to assess the impact of subcellular CD133 expression on the clinical course of endometrial cancer. (2) Methods: CD133 expression in the plasma membrane, nucleus, and cytoplasm was assessed by immunohistochemical staining in a group of 64 patients with endometrial cancer representing FIGO I-IV stages, grades 1–3 and accounting for tumor angioinvasion. (3) Results: Nuclear localization of CD133 expression was increased in FIGO IB-IV stages compared to FIGO IA. Furthermore, CD133 expression in the nucleus and plasma membrane is positively and negatively associated with a higher grade of endometrial cancer and angioinvasion, respectively. (4) Conclusions: Our findings suggest that positive nuclear CD133 expression in the tumor may be related to a less favorable prognosis of endometrial carcinoma patients and has emerged as a useful biomarker of a high-risk group.

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1367
Author(s):  
Kristina Lindemann ◽  
Elisabeth Smogeli ◽  
Milada Cvancarova Småstuen ◽  
Kjersti Bruheim ◽  
Jone Trovik ◽  
...  

(1) Background: This study evaluated the clinical outcome after salvage radiotherapy for first pelvic relapse after endometrial cancer (EC). (2) Methods: This multicenter retrospective study included EC patients with first central pelvic relapse without lymph node involvement treated with curative intent. Progression-free (PFS) and overall survival (OS) were calculated with the Kaplan–Meier method and possible predictive factors for risk of relapse and mortality were identified using the Cox model. (3) Results: We included 139 patients with median EQD2 (Equivalent Dose in 2 Gy fractions) to the clinical target volume of 70.0 Gy. During follow up of median 6.66 years, 39.6% patients developed a second relapse. Risk group classification at primary diagnosis based on histology, grading and FIGO stage and how the pelvic tumor boost was administered were independently associated with PFS and OS. Five-year OS was 68% (95% CI (59–75)) for the whole cohort. Five-year OS was 88% (95% CI (75–94)), 72% (95% CI (55–84)) and 38% (95% CI (15–60)) for the stage I low-, intermediate- and high-risk group, respectively. (4) Conclusions: The majority of central pelvic recurrences in RT-naive EC women can be successfully salvaged with radiotherapy. However, survival in patients with high-risk disease remains poor and warrants a more individualized approach to optimize outcome.


2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Ziwei Wang ◽  
Jun Zhang ◽  
Yan Liu ◽  
Rong Zhao ◽  
Xing Zhou ◽  
...  

Endometrial cancer is one of the most common malignant tumors, lowering the quality of life among women worldwide. Autophagy plays dual roles in these malignancies. To search for prognostic markers for endometrial cancer, we mined The Cancer Genome Atlas and the Human Autophagy Database for information on endometrial cancer and autophagy-related genes and identified five autophagy-related long noncoding RNAs (lncRNAs) (LINC01871, SCARNA9, SOS1-IT1, AL161618.1, and FIRRE). Based on these autophagy-related lncRNAs, samples were divided into high-risk and low-risk groups. Survival analysis showed that the survival rate of the high-risk group was significantly lower than that of the low-risk group. Univariate and multivariate independent prognostic analyses showed that patients’ age, pathological grade, and FIGO stage were all risk factors for poor prognosis. A clinical correlation analysis of the relationship between the five autophagy-related lncRNAs and patients’ age, pathological grade, and FIGO stage was also per https://orcid.org/0000-0001-7090-1750 formed. Histopathological assessment of the tumor microenvironment showed that the ESTIMATE, immune, and stromal scores in the high-risk group were lower than those in the low-risk group. Principal component analysis and functional annotation were performed to confirm the correlations. To further evaluate the effect of the model constructed on prognosis, samples were divided into training (60%) and validation (40%) groups, regarding the risk status as an independent prognostic risk factor. A prognostic nomogram was constructed using patients’ age, pathological grade, FIGO stage, and risk status to estimate the patients’ survival rate. C-index and multi-index ROC curves were generated to verify the stability and accuracy of the nomogram. From this analysis, we concluded that the five lncRNAs identified in this study could affect the incidence and development of endometrial cancer by regulating the autophagy process. Therefore, these molecules may have the potential to serve as novel therapeutic targets and biomarkers.


2021 ◽  
pp. ijgc-2021-002582
Author(s):  
Gitte Ortoft ◽  
Claus Høgdall ◽  
Estrid Stæhr Hansen ◽  
Margit Dueholm

ObjectiveTo compare the performance of the new ESGO-ESTRO-ESP (European Society of Gynecological Oncology-European Society for Radiotherapy & Oncology-European Society for Pathology) 2020 risk classification system with the previous 2016 risk classification in predicting survival and patterns of recurrence in the Danish endometrial cancer population.MethodsThis Danish national cohort study included 4516 patients with endometrial cancer treated between 2005 and 2012. Five-year Kaplan–Meier adjusted and unadjusted survival estimates and actuarial recurrence rates were calculated for the previous and the new classification systems.ResultsIn the 2020 risk classification system, 81.0% of patients were allocated to low, intermediate, or high-intermediate risk compared with 69.1% in the 2016 risk classification system, mainly due to reclassification of 44.5% of patients previously classified as high risk to either intermediate or especially high-intermediate risk. The survival of the 2020 high-risk group was significantly lower, and the recurrence rate, especially the non-local recurrence rate, was significantly higher than in the 2016 high risk group (2020/2016, overall survival 59%/66%; disease specific 69%/76%; recurrence 40.5%/32.3%, non-local 34.5%/25.8%). Survival and recurrence rates in the other risk groups and the decline in overall and disease-specific survival rates from the low risk to the higher risk groups were similar in patients classified according to the 2016 and 2020 systems.ConclusionThe new ESGO-ESTRO-ESP 2020 risk classification system allocated fewer patients to the high risk group than the previous risk classification system. The main differences were lower overall and disease-specific survival and a higher recurrence rate in the 2020 high risk group. The introduction of the new 2020 risk classification will potentially result in fewer patients at high risk and allocation to the new high risk group will predict lower survival, potentially allowing more specific selection for postoperative adjuvant therapy.


2020 ◽  
Vol 9 (7) ◽  
pp. 2057
Author(s):  
Vanja Ristovic ◽  
Sophie de Roock ◽  
Thierry G. Mesana ◽  
Sean van Diepen ◽  
Louise Y. Sun

Background: Despite steady improvements in cardiac surgery-related outcomes, our understanding of the physiologic mechanisms leading to perioperative mortality remains incomplete. Intraoperative hypotension is an important risk factor for mortality after noncardiac surgery but remains relatively unexplored in the context of cardiac surgery. We examined whether the association between intraoperative hypotension and in-hospital mortality varied by patient and procedure characteristics, as defined by the validated Cardiac Anesthesia Risk Evaluation (CARE) mortality risk score. Methods: We conducted a retrospective cohort study of consecutive adult patients who underwent cardiac surgery requiring cardiopulmonary bypass (CPB) from November 2009–March 2015. Those who underwent off-pump, thoracic aorta, transplant and ventricular assist device procedures were excluded. The primary outcome was in-hospital mortality. Hypotension was categorized by mean arterial pressure (MAP) of <55 and between 55–64 mmHg before, during and after CPB. The relationship between hypotension and death was modeled using multivariable logistic regression in the intermediate and high-risk groups. Results: Among 6627 included patients, 131 (2%) died in-hospital. In-hospital mortality in patients with CARE scores of 1, 2, 3, 4 and 5 was 0 (0%), 7 (0.3%), 35 (1.3%), 41 (4.6%) and 48 (13.6%), respectively. In the intermediate-risk group (CARE = 3–4), MAP < 65 mmHg post-CPB was associated with increased odds of death in a dose-dependent fashion (adjusted OR 1.30, 95% CI 1.13–1.49, per 10 min exposure to MAP < 55 mmHg, p = 0.002; adjusted OR 1.18 [1.07–1.30] per 10 min exposure to MAP 55–64 mmHg, p = 0.001). We did not observe an association between hypotension and mortality in the high-risk group (CARE = 5). Conclusions: Post-CPB hypotension is a potentially modifiable risk factor for mortality in intermediate-risk patients. Our findings provide impetus for clinical trials to determine if hemodynamic goal-directed therapies could improve survival in these patients.


2020 ◽  
Vol 21 (14) ◽  
pp. 995-1010
Author(s):  
Sara Gagno ◽  
Michele Bartoletti ◽  
Chiara Romualdi ◽  
Elena Poletto ◽  
Simona Scalone ◽  
...  

Aim: To define the impact of polymorphisms in genes involved in platinum-taxane and estrogen activity in the outcome of platinum-based treated ovarian cancer patients (OCP). Patients & Methods: Two hundred and thirty OCP were analyzed for 124 germ-line polymorphisms to generate a prognostic score for overall survival (OS), progression-free survival (PFS) and platinum-free interval (PFI). Results: ABCG2 rs3219191D>I, UGT1A rs10929302G>A and UGT1A rs2741045T>C polymorphisms were significantly associated with all three parameters (OS, PFS and PFI) and were used to generate a score. Patients in high-risk group had a poorer OS (hazard ratio [HR]: 1.8; 95% CI: 1.3–2.7; p = 0.0019), PFS (HR: 2.0; 95% CI: 1.4–2.9; p < 0.0001) and PFI (HR: 1.9; 95% CI: 1.4–2.8; p = 0.0002) compared with those in low-risk group. Conclusion: The prognostic-score including polymorphisms involved in drug and estrogen pathways stratifies OCP according to OS, PFS and PFI.


2000 ◽  
Vol 70 ◽  
pp. D101-D101
Author(s):  
E.V. Elnogarr ◽  
U.U. Tabakman ◽  
A.E. Ivanov ◽  
Z.M. Vahturova ◽  
A.G. Solopova

2020 ◽  
Vol 30 (10) ◽  
pp. 1513-1519 ◽  
Author(s):  
Alyssa Larish ◽  
Amanika Kumar ◽  
Amy Weaver ◽  
Andrea Mariani

ObjectivePrevious studies have investigated the impact of preoperative hysteroscopy on the staging and survival of predominantly grade 1 endometrial cancers. We sought to evaluate the effect of hysteroscopy on the peritoneal spread of tumor cells and disease course in a large series of patients with high-risk endometrial cancer.MethodsPatients who underwent hysterectomy for grade 3 endometrial carcinoma on final surgical pathology at the Mayo Clinic in Rochester, MN between January 2009 to June 2016 were included, noting hysteroscopy within 6 months from surgery. Intra-peritoneal disease was defined as any positive cytology OR adnexal invasion OR stage IV. The presence of intra-peritoneal disease OR peritoneal recurrence within 2 years from surgery was defined as peritoneal dissemination. Cox proportional hazards models were fit to evaluate associations between hysteroscopy exposure and progression within 5 years following surgery.ResultsAmong 831 patients, 133 underwent hysteroscopy. There was no difference in age, body mass index, ASA ≥3, or serous histology between patients who did or did not undergo hysteroscopy. Advanced stage disease (III/IV) was less common among patients who underwent hysteroscopy (30.1% vs 43.8%, P=0.003). No difference was observed between those with vs without hysteroscopy in the rate of positive cytology (22.0% vs 29.7%, P=0.09), stage IV (16.5% vs 21.9%, P=0.16), intra-peritoneal disease (28.6% vs 36.1%, P=0.09), or peritoneal dissemination (30.8% vs 39.3%, P=0.06). On stratifying by stage, hysteroscopy did not increase the risk of progression (HR 1.06, 95% CI 0.59 to 1.92 for stage I/II; HR 0.96, 95% CI 0.62 to 1.48 for stage III/IV).ConclusionIn this retrospective study of grade 3 endometrial cancer, we did not observe any significant association between pre-operative hysteroscopy and the incidence of positive cytology, peritoneal disease, peritoneal dissemination, or cancer progression.


2021 ◽  
Author(s):  
Shenglan Huang ◽  
Jian Zhang ◽  
Dan Li ◽  
Xiaolan Lai ◽  
Lingling Zhuang ◽  
...  

Abstract Introduction: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors with poor prognosis. Tumor microenvironment (TME) plays a vital role in the tumor progression of HCC. Thus, we aimed to analyze the association of TME with HCC prognosis, and construct an TME-related lncRNAs signature for predicting the prognosis of HCC patients.Methods: We firstly assessed the stromal/immune /Estimate scores within the HCC microenvironment using the ESTIMATE algorithm based on TCGA database, and its associations with survival and clinicopathological parameters were also analyzed. Then, different expression lncRNAs were filtered out according to immune/stromal scores. Cox regression was performed to built an TME-related lncRNAs risk signature. Kaplan–Meier analysis was carried out to explored the prognostic values of the risk signature. Furthermore, we explored the biological functions and immune microenvironment feathers in high- and low risk groups. Lastly, we probed the association of the risk signature with the treatment responses to immune checkpoint inhibitors (ICIs) in HCC by comparing the immunophenoscore (IPS).Results: Stromal/immune /Estimate scores of HCC patients were obtained based on the ESTIMATE algorithm. The Kaplan-Meier curve analysis showed the high stromal/immune/ Estimate scores were significantly associated with better prognosis of the HCC patients. Then, six TME-related lncRNAs were screened for constructing the prognosis model. Kaplan-Meier survival curves suggested that HCC patients in high-risk group had worse prognosis than those with low-risk. ROC curve and Cox regression analyses demonstrated the signature could predict HCC survival exactly and independently. Function enrichment analysis revealed that some tumor- and immune-related pathways associated with HCC tumorigenesis and progression might be activated in high-risk group. We also discovered that some immune cells, which were beneficial to enhance immune responses towards cancer, were remarkably upregulated in low-risk group. Besides, there was closely correlation of immune checkmate inhibitors (ICIs) with the risk signature and the signature can be used to predict treatment response of ICIs.Conclusions: We analyzed the impact of the tumor microenvironment scores on the prognosis of patients with HCC. A novel TME-related prognostic risk signature was established, which may improve prognostic predictive accuracy and guide individualized immunotherapy for HCC patients.


2017 ◽  
pp. 351-363 ◽  
Author(s):  
Ana B Crujeiras ◽  
Angel Diaz-Lagares ◽  
Olafur A Stefansson ◽  
Manuel Macias-Gonzalez ◽  
Juan Sandoval ◽  
...  

Obesity is a high risk factor for breast cancer. This relationship could be marked by a specific methylome. The current work was aimed to explore the impact of obesity and menopausal status on variation in breast cancer methylomes. Data from Infinium 450K array-based methylomes of 64 breast tumors were coupled with information on BMI and menopausal status. Additionally, DNA methylation results were validated in 18 non-tumor and 81 tumor breast samples. Breast tumors arising in either pre- or postmenopausal women stratified by BMI or menopausal status alone were not associated with a specific DNA methylation pattern. Intriguingly, the DNA methylation pattern identified in association with the high-risk group (postmenopausal women with high BMI (>25) and premenopausal women with normal or low BMI < 25) exclusively characterized by hypermethylation of 1287 CpG sites as compared with the low-risk group. These CpG sites included the promoter region of fourteen protein-coding genes of which CpG methylation over the ZNF577 promoter region represents the top scoring associated event. In an independent cohort, the ZNF577 promoter methylation remained statistically significant in association with the high-risk group. Additionally, the impact of ZNF577 promoter methylation on mRNA expression levels was demonstrated in breast cancer cell lines after treatment with a demethylating agent (5-azacytidine). In conclusion, the epigenome of breast tumors is affected by a complex interaction between BMI and menopausal status. The ZNF577 methylation quantification is clearly relevant for the development of novel biomarkers of precision therapy in breast cancer.


2021 ◽  
Vol 104 (1) ◽  
pp. 003685042110065
Author(s):  
Jing Wan ◽  
Peigen Chen ◽  
Yu Zhang ◽  
Jie Ding ◽  
Yuebo Yang ◽  
...  

Endometrial carcinoma (EC) is the fourth most common cancer in women. Some long non-coding RNAs (lncRNAs) are regarded as potential prognostic biomarkers or targets for treatment of many types of cancers. We aim to screen prognostic-related lncRNAs and build a possible lncRNA signature which can effectively predict the survival of patients with EC. We obtained lncRNA expression profiling from the TCGA database. The patients were classified into training set and verification set. By performing Univariate Cox regression model, Robust likelihood-based survival analysis, and Cox proportional hazards model, we developed a risk score with the Cox co-efficient of individual lncRNAs in the training set. The optimum cut-off point was selected by ROC analysis. Patients were effectively divided into high-risk group and low-risk group according to the risk score. The OS of the low-risk patients was significantly prolonged compared with that of the high-risk group. At last, we validated this 11-lncRNA signature in the verification set and the complete set. We identified an 11-lncRNA expression signature with high stability and feasibility, which can predict the survival of patients with EC. These findings provide new potential biomarkers to improve the accuracy of prognosis prediction of EC.


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