Diagnostic Value of MicroRNA 21 in Endometrial Cancer and Benign Lesions and its Differential Expression in Relation to Clinicopathological Parameters

MicroRNA ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Amal Bouziyane ◽  
Maryame Lamsisi ◽  
Hicham Benaguida ◽  
Mustapha Benhessou ◽  
Mohamed El Kerroumi ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Characteristic Curve ◽  
Myometrial Invasion ◽  
Figo Stage ◽  
Diagnostic Value ◽  
Clinicopathological Parameters ◽  
Benign Lesions ◽  
Tumor Tissues ◽  
Potential Biomarker ◽  
Noninvasive Samples

Background: Endometrial cancer is one of the most common malignancies among women worldwide. Although this cancer is often diagnosed at early stages, the need for biomarkers of diagnosis remains a necessity to overcome conventional invasive procedures of diagnosis. Objective: In our study, we aim to investigate the diagnostic value of microRNA-21 in endometrial cancer and its relation to clinicopathological features. Methods: We used RT-qPCR to measure the expression of microRNA-21 in 71 tumor tissues, 53 adjacent tissues, and 54 benign lesions. Results: Our results show that microRNA-21 is a potential biomarker for endometrial cancer with an area under the receiver operating characteristic curve of 0.925 (95% CI = 0.863 - 0.964, P<0.0001). The sensitivity was 84.51% (95% CI = 74.0 - 92.0) and specificity was 86.79% (95% CI = 74.7 - 94.5). For discrimination between benign lesions and controls the AUC was 0,881 with a sensitivity of 100% (95% CI = 93.4 - 100.0) and specificity of 66.04 % (95% CI = 51.7 - 78.5), and for discriminating benign lesions from tumors the AUC was 0,750 with a sensitivity of 54.93% (95% CI = 42.7 - 66.8) and specificity of 90.74% (95% CI = 79.7 - 96.9). We also found that tumors with elevated microRNA-21 expression are of advanced FIGO stage, high histological grades, and have cervical invasion, myometrial invasion and distant metastasis. Conclusion: Our findings support the important role of miR-21 as a biomarker for the diagnosis of endometrial cancer. Further studies on minimally invasive/noninvasive samples such as serum, blood, and urine are necessary to provide a better alternative to current diagnosis methods.

Bioinformatics Analysis of Tumor-Associated Macrophages, Vascular Endothelial Growth Factor and Microvascular Density in Endometrial Carcinomas

2020 ◽  
Vol 10 (6) ◽  
pp. 1321-1326
Author(s):  
Lili Yue ◽  
Wen Shi ◽  
Kao Li ◽  
Jingwen Shi ◽  
Yi Lian ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Endometrial Cancer ◽  
Growth Factor ◽  
Myometrial Invasion ◽  
Tumor Stroma ◽  
Figo Stage ◽  
Microvascular Density ◽  
Clinicopathological Parameters ◽  
Vascular Endothelial ◽  
Endothelial Growth Factor

Objective: The aim of our study was to investigate the expression of tumor-associated macrophage (TAMs), Vascular Endothelial Growth Factor (VEGF) and regional microvascular density (MVD) in different parts of the endometrial carcinoma based on bioinformatics. Methods: Immunohistochemistry assay were used to detect the density of TAMs in endometrial cancer nest, tumor stroma, and infiltrating marginal and its relationship with clinicopathological parameters, VEGF and MVD. Results: To compare with normal tissue, the TAMs in tumor stroma, cancer nest and infiltrating marginal were significantly higher. The density of TAMs in infiltrating marginal was correlated to the FIGO stage, histological grade, myometrial invasion and also lymph node metastasis in endometrial cancer; while the TAMs in tumor stroma is not related to the FIGO stage. Positive correlation between the density of TAMs in tumor stroma, infiltrating marginal and VEGF and MVD in endometrial cancer was found. Conclusion: The change of tumor microenvironment caused by increased density of TAMs promote tumor microangiogenesis and aggravate the progression of endometrial cancer.

Heparanase expression and angiogenesis in endometrial cancer: Analyses of RT-PCR and immunohistochemistry

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5535-5535
Author(s):  
Y. Aoki ◽  
M. Inamine ◽  
M. Hirakawa ◽  
W. Kudaka ◽  
Y. Nagai
Keyword(s):  
Endometrial Cancer ◽  
Tumor Angiogenesis ◽  
Microvessel Density ◽  
Myometrial Invasion ◽  
Tumor Grade ◽  
Figo Stage ◽  
Clinicopathological Parameters ◽  
Strong Positive Correlation ◽  
Stage Iiic ◽  
Endometrial Cancers

5535 Background: The human heparanase has been shown to function in tumor progression, metastatic spread, and tumor angiogenesis. The aim of the present study was to assess heparanase expression in endometrial cancer in correlation with neovascularization and clinicopathological factors.Methods: Fifty-two endometrial cancers were obtained from previously untreated patients (median age, 56 years; range, 35–80 years). The expression of heparanase mRNA was evaluated using a semi-quantitative reverse transcriptase-polymerase chain reaction and immunohistochemical staining (IHC) with anti-heparanase polyclonal antibody. This antibody was raised by immunizing a rabbit with a peptide containing the amino acid residues from 238 to 250 of the Heparanase. Tumor angiogenesis was assessed using microvessel counting. The Mann-Whitney U test, one factor ANOVA test, and Spearman's test were used to determine the relationship between heparanase expression, microvessel density, and clinicopathological parameters. Results: The expression of heparanase mRNA was detected in 26 of 52 (50%) endometrial cancers, and was significantly correlated with FIGO stage IIIc (p = 0.0075), the presence of lymph-vascular space involvement (LVSI) (p = 0.0041), lymph node metastasis (LNM) (p = 0.0049), and histological tumor grade (p = 0.003). IHC showed that the heparanase was expressed in 23 of 52 (44.2%) endometrial cancers, which was significantly related to LVSI (p = 0.0028), depth of myometrial invasion (p = 0.0026), and histological tumor grade (p = 0.0135). Microvessel density was also associated with FIGO stage IIIc (p = 0.027), LVSI (p = 0.001), LNM (p = 0.038), ovarian metastasis (p = 0.03) and histological tumor grade (p = 0.003). Moreover, we found a strong positive correlation between heparanase expression and microvessel density (r2 = 0.475, p = 0.0001). Conclusions: These results suggest that the expression of heparanase can promote tumor angiogenesis and develop metastasis in endometrial cancer. No significant financial relationships to disclose.

Clinicopathological significance and prognostic value of intratumoral and peritumoral lymphocytes in endometrial cancer patients.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e17116-e17116
Author(s):  
Martin Ore-Arce ◽  
Carmen Illueca Ballester ◽  
Raquel Lopez-Reig ◽  
Monica Parra-Grande ◽  
Ignacio Romero ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Prognostic Value ◽  
Cytotoxic T Cells ◽  
Myometrial Invasion ◽  
Tumor Infiltrating Lymphocytes ◽  
Tp53 Gene ◽  
Figo Stage ◽  
Tumor Stage ◽  
Stage I ◽  
Clinicopathological Parameters

e17116 Background: The characterization and prognostic relevance of immune cells in the tumor microenvironment of endometrial cancer (EC) remain unknown. Our aims are to analyze the presence of tumor infiltrating lymphocytes (TIL) and peritumoral lymphocytes (PTL) in tumoral tissue of patients with EC, and to identify the correlation between TILs and PTLs subsets with clinicopathologic features and its prognostic value Methods: CD3, CD4, CD8, CD20, and FOXP-3 was determined by immunohistochemestry (IHQ). A 4-point score was defined based on TIL counts per highpowered field: (negative, low, moderate, and high). We used 10% positive peritumoral lymphocytes as a low-high cutoff value. POLE mutation was identified by Sanger sequencing of the exonuclease domain (exons 9-14). Analysis of mismatch repair expression and TP53 gene mutation status were assessed. Results from IHQ and analysis mutation were correlated with clinicopathological parameters and survival. Results: We recovered tumor samples from 68 FIGO stage I–IV EC patients. POLE mutations were identified in 5 of 44 (11.4%) EC analyzed. Microsatellite instability (MSI) and TP53 mutation were found in 45% and 25 % of cases respectively. According PTL, MSI tumors were significantly associated with low CD4+ (p = 0.01). High CD8+ was significantly associated with endometrioid grade 1-2 tumors (p = 0.04). Low FOXP3+ was significantly associated with endometrioid grade 1-2 (p = 0.02), MSS tumors (p < 0.01), FIGO stage I-II (p < 0.01), POLE WT (p < 0.01), TP53 WT (p < 0.01), and negative lymphovascular space invasion (p < 0.01). Negative CD20+ TIL was associated with endometrioid grade 1-2 tumors (p < 0.01) and ≥50% myometrial invasion (p = 0.03). Moderate CD8+ TIL was associated with lower tumor stage (p = 0.01). High CD8+ TIL was associated with better 5-year overall survival (OS) rate (high: 100 % vs. low: 53%; p = 0.003). No significant association was observed between POLE status, TP53 status, MMR expression and survival. Conclusions: Regulatory and cytotoxic T cells subsets differs in EC patients. High CD8+ TILs was significantly associated with better 5-year OS.

Three plasma-based microRNAs as potent diagnostic biomarkers for endometrial cancer

2021 ◽  
pp. 1-12
Author(s):  
Xingchen Fan ◽  
Minmin Cao ◽  
Cheng Liu ◽  
Cheng Zhang ◽  
Chunyu Li ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Operating Characteristic ◽  
Characteristic Curve ◽  
External Validation ◽  
Diagnostic Value ◽  
Diagnostic Biomarkers ◽  
Non Invasive ◽  
Polymerase Chain ◽  
Public Datasets ◽  
Plasma Mirnas

BACKGROUND: MicroRNAs (miRNAs), with noticeable stability and unique expression pattern in plasma of patients with various diseases, are powerful non-invasive biomarkers for cancer detection including endometrial cancer (EC). OBJECTIVE: The objective of this study was to identify promising miRNA biomarkers in plasma to assist the clinical screening of EC. METHODS: A total of 93 EC and 79 normal control (NC) plasma samples were analyzed using Quantitative Real-time Polymerase Chain Reaction (qRT-PCR) in this four-stage experiment. The receiver operating characteristic curve (ROC) analysis was conducted to evaluate the diagnostic value. Additionally, the expression features of the identified miRNAs were further explored in tissues and plasma exosomes samples. RESULTS: The expression of miR-142-3p, miR-146a-5p, and miR-151a-5p was significantly overexpressed in the plasma of EC patients compared with NCs. Areas under the ROC curve of the 3-miRNA signature were 0.729, 0.751, and 0.789 for the training, testing, and external validation phases, respectively. The diagnostic performance of the identified signature proved to be stable in the three public datasets and superior to the other miRNA biomarkers in EC diagnosis. Moreover, the expression of miR-151a-5p was significantly elevated in EC plasma exosomes. CONCLUSIONS: A signature consisting of 3 plasma miRNAs was identified and showed potential for the non-invasive diagnosis of EC.

Characteristics of early-stage endometrial cancer and factors that influence disease recurrence.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e17567-e17567
Author(s):  
Su Yun Chung ◽  
Janice Shen ◽  
Nina Kohn ◽  
Jennifer Hernandez ◽  
Marina Frimer ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Adjuvant Therapy ◽  
Tumor Size ◽  
Early Stage ◽  
Univariate Analysis ◽  
Multivariable Analysis ◽  
Myometrial Invasion ◽  
Figo Stage ◽  
Risk Of Recurrence ◽  
Early Stage Endometrial Cancer

e17567 Background: Early-stage endometrial cancer (EEC) with FIGO stage I-II generally has a favorable prognosis and overall survival (OS). However, up to 10% of EEC patients (pts) relapse and risk factors for recurrence remain unclear. We evaluated clinical and histopathologic characteristics of EEC and correlated them with OS and recurrence free survival (RFS) through a single-center retrospective analysis. Methods: We conducted a retrospective chart review on 511 pts with EEC identified by our cancer registry from 1/1/2009 to 12/31/2019. The two main histologic groups were endometrioid adenocarcinomas (E) and other subtypes (O) including carcinosarcoma, undifferentiated, and clear cell carcinomas. Papillary serous histology was excluded. Histopathologic and clinical findings recorded included age, FIGO stage and grade, tumor size, presence of recurrence, adjuvant therapies received, percent of myometrial invasion (MI), and lymphovascular invasion (LVI). OS and RFS were estimated, and each predictor was compared using the log-rank test. The association between OS and each continuous characteristic was examined using the Cox proportional hazards model. Factors significantly associated with OS and RFS in the univariable analysis (p < 0.05) were included in a multivariable analysis to examine the joint effects of those factors on survival. Results: A total of 511 cases were reviewed. The analysis included 501 pts (E = 485, O = 16), of which 47 had recurrent disease (E = 45, O = 2) and 17 had died without recurring (E = 15, O = 2) as of their last follow-up. Overall median age was 63 years. Factors significantly associated with recurrence in the multivariable analysis were FIGO grade, (Hazard Ratios (HR): Grade 2 vs 1: 1.95, 95% CI: 1.06-3.58, p = 0.0320, Grade 3 vs 1: 2.88, 95% CI: 1.50-5.52, p = 0.0015), LVI (HR: 2.03, 95% CI: 1.10-3.75, p = 0.0244), and greater than 50% of MI (HR: 3.15, 95% CI: 1.35-7.36, p = 0.0080). The overall RFS was 92% and 86% at three and five years, respectively. On univariate analysis, among pts with a measurable tumor size (n = 446), larger tumors were not significantly associated with OS (p = 0.65) but was associated with increased recurrence (HR 1.22, 95% CI: 1.10-1.37, for a unit increase, p = 0.0003). On univariate analysis, pts who received adjuvant therapy were more likely to recur (p = 0.0002) with RFS of 86% and 76% at three and five years respectively, versus RFS of 94% and 90%, for those who did not. Conclusions: We confirmed the clinical and histopathologic characteristics that are currently considered to increase risk of recurrence in EEC. On multivariate analysis, risk of recurrence was associated with FIGO grades 2 and 3, presence of LVI, and > 50% MI. A limitation of this study is the lack of molecular analysis. Further molecular stratification may help us identify the subset of pts who are at high risk of recurrence, enabling customized adjuvant therapy in EEC.

scholarly journals Clinical value of selected markers of angiogenesis, inflammation, insulin resistance and obesity in type 1 endometrial cancer

2020 ◽  
Author(s):  
Katarzyna M. Terlikowska ◽  
Bozena Dobrzycka ◽  
Robert Terlikowski ◽  
Anna Sienkiewicz ◽  
Maciej Kinalski ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Endometrial Cancer ◽  
Growth Factor ◽  
Myometrial Invasion ◽  
Serum Levels ◽  
Figo Stage ◽  
Cancer Type ◽  
Cox Regression Analysis ◽  
Angiopoietin 2

Abstract Background: It is a well-known fact show that the risk of developing endometrial cancer (type 1 EC) is strongly associated with obesity. In this study, selected markers, such as obesity, insulin resistance, angiogenesis and inflammation markers related to EC type 1 progression and patients’ survival data were analyzed.Methods: To measure levels of adiponectin, C-reactive protein (CRP), vascular endothelial growth factor-A (VEGF-A), angiopoietin-2 (Ang-2), insulin-like growth factor-1 (IGF-1), insulin and C-peptide in 176 preoperative serum samples, the immunoassay technique (EMIT) has been applied.Results: Angiopoietin-2 levels increase with age (P=0.005), FIGO stage (p=0.042), myometrial invasion (P=0.009) and LVSI (P<0.001). The CRP levels increase with age (P=0.01), as well as the advancement of the FIGO stage (P<0.001), higher tumor grade (P=0.012), and myometrial invasion (P<0.001). A positive correlation between serum Ang-2 and CRP levels was demonstrated (r=0.44; p<0.001). Kaplan-Meier survival analysis showed that patients with high CRP levels in serum and Ang-2 presented a worse outcome (P=0.03 and P=0.015, respectively). Cox regression analysis of individual predictors revealed that high serum levels of Ang-2, CRP, advanced clinical FIGO stage (P<0.001, respectively), old age (P=0.013) were all significant overall survival predictors. By means of multivariate analysis, their predictive significance was confirmed.Conclusion: Our study provides evidence that serum levels of Ang-2 and CRP may serve as predictors for assessment of the clinical stage of type 1 EC and are significantly associated with poor prognosis. It is likely that angiogenesis and inflammation associated with obesity have a significant impact on EC type 1 progression and survival rate of patients.

scholarly journals Tumoral volume measured preoperatively by magnetic resonance imaging is related to survival in endometrial cancer

2021 ◽  
Vol 55 (1) ◽  
pp. 35-41
Author(s):  
Pluvio J. Coronado ◽  
Javier de Santiago-López ◽  
Javier de Santiago-García ◽  
Ramiro Méndez ◽  
Maria Fasero ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Endometrial Cancer ◽  
Magnetic Resonance ◽  
Auxiliary Information ◽  
Myometrial Invasion ◽  
Figo Stage ◽  
Mri Imaging ◽  
Resonance Imaging ◽  
Deep Myometrial Invasion ◽  
Grade 3

AbstractBackgroundThe aim of the study was to determine if the endometrial tumor volume (TV) measured by magnetic resonance imaging (MRI-TV) is associated with survival in endometrial cancer and lymph nodes metastases (LN+).Patients and methodsWe evaluated the MRI imaging and records of 341 women with endometrial cancer and preoperative MRI from 2008 to 2018. The MRI-TV was calculated using the ellipsoid formula measuring three perpendicular tumor diameters. Tumor myometrial invasion was also analyzed.ResultsHigher MRI-TV was associated with age ≥ 65y, non-endometrioid tumors, grade-3, deep-myometrial invasion, LN+ and advanced FIGO stage. There were 37 patients with LN+ (8.8%). Non-endometrioid tumors, deep-myometrial invasion, grade-3 and MRI-TV ≥ 10 cm3 were the factors associated with LN+. Using a receiver operating characteristic [ROC] curve, the MRI-TV cut-off for survival was 10 cm3 (area under curve [AUC] = 0.70; 95% CI: 0.61–0.73). 5 years disease-free (DFS) and overall survival (OS) was significantly lower in MRI-TV ≥ 10 cm3 (69.3% vs. 84.5%, and 75.4% vs. 96.1%, respectively). MRI-TV was considered an independent factor of DFS (HR: 2.20, 95% CI: 1.09–4.45, p = 0.029) and OS (HR: 3.88, 95% CI: 1.34–11.24, p = 0.012) in multivariate analysis.ConclusionsMRI-TV was associated with LN+, and MRI-TV ≥ 10 cm3 was an independent prognostic factor of lower DFS and OS. The MRI-TV can be auxiliary information to plan the surgery strategy and predict the adjuvant treatment in women with endometrial cancer.

Heparanase expression in both normal endometrium and endometrial cancer

2006 ◽  
Vol 16 (3) ◽  
pp. 1401-1406 ◽  
Author(s):  
J. Kodama ◽  
T. Kusumoto ◽  
N. Seki ◽  
T. Matsuo ◽  
Y. Ojima ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Survival Rates ◽  
Myometrial Invasion ◽  
Immunohistochemical Analysis ◽  
Figo Stage ◽  
Peritoneal Cytology ◽  
Normal Endometrium ◽  
Deep Myometrial Invasion ◽  
Endometrial Cancers ◽  
The Relationship

The aim of this study was to investigate the relationship between heparanase expression and prognostic factors in endometrial cancer, as well as the relationship between heparanase expression during phases of the normal endometrial cycle. Immunohistochemical analysis of 166 endometrial cancers and 34 normal endometria in various phases of growth was performed. The heparanase expression in the late-proliferative phase of normal endometria was found to be significantly higher than in either the early-proliferative or the secretory phases (P = .012 and P = .044, respectively). Heparanase expression was also significantly higher in endometrial cancer patients with tumors of an advanced FIGO stage (P = .0003) and high FIGO grade (P = .004) and with cancers showing either deep myometrial invasion (P = .023), lymph node metastasis (P = .006), lymphvascular space involvement (P = .048), or positive peritoneal cytology (P = .010). The disease-free and overall survival rates of patients with intense heparanase expression were significantly lower than those of patients with absent or moderate heparanase expression (P = .004 and P = .002, respectively). Heparanase may participate in normal endometrial remodeling and can serve as an indicator of the aggressive potential and poor prognosis of endometrial cancers.

scholarly journals Exploring lncRNA-Mediated Regulatory Networks in Endometrial Cancer Cells and the Tumor Microenvironment: Advances and Challenges

Cancers ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 234 ◽  
Author(s):  
Peixin Dong ◽  
Ying Xiong ◽  
Junming Yue ◽  
Sharon J. B. Hanley ◽  
Noriko Kobayashi ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Tumor Microenvironment ◽  
Signaling Pathways ◽  
Regulatory Networks ◽  
Myometrial Invasion ◽  
Tumor Grade ◽  
Figo Stage ◽  
Normal Tissues ◽  
P53 Signaling ◽  
Ec Cells

Recent studies have revealed both the promise and challenges of targeting long non-coding RNAs (lncRNAs) to diagnose and treat endometrial cancer (EC). LncRNAs are upregulated or downregulated in ECs compared to normal tissues and their dysregulation has been linked to tumor grade, FIGO stage, the depth of myometrial invasion, lymph node metastasis and patient survival. Tumor suppressive lncRNAs (GAS5, MEG3, FER1L4 and LINC00672) and oncogenic lncRNAs (CCAT2, BANCR, NEAT1, MALAT1, H19 and Linc-RoR) have been identified as upstream modulators or downstream effectors of major signaling pathways influencing EC metastasis, including the PTEN/PI3K/AKT/mTOR, RAS/RAF/MEK/ERK, WNT/β-catenin and p53 signaling pathways. TUG1 and TDRG1 stimulate the VEGF-A pathway. PCGEM1 is implicated in activating the JAK/STAT3 pathway. Here, we present an overview of the expression pattern, prognostic value, biological function of lncRNAs in EC cells and their roles within the tumor microenvironment, focusing on the influence of lncRNAs on established EC-relevant pathways. We also describe the emerging classification of EC subtypes based on their lncRNA signature and discuss the clinical implications of lncRNAs as valuable biomarkers for EC diagnosis and potential targets for EC treatment.

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