Endometrial Carcinoma Patients Research Articles

MRI-based radiomics and ADC values are related to recurrence of endometrial carcinoma: a preliminary analysis

BackgroundTo identify predictive value of apparent diffusion coefficient (ADC) values and magnetic resonance imaging (MRI)-based radiomics for all recurrences in patients with endometrial carcinoma (EC).MethodsOne hundred and seventy-four EC patients who were treated with operation and followed up in our institution were retrospectively reviewed, and the patients were divided into training and test group. Baseline clinicopathological features and mean ADC (ADCmean), minimum ADC (ADCmin), and maximum ADC (ADCmax) were analyzed. Radiomic parameters were extracted on T2 weighted images and screened by logistic regression, and then a radiomics signature was developed to calculate the radiomic score (radscore). In training group, Kaplan–Meier analysis was performed and a Cox regression model was used to evaluate the correlation between clinicopathological features, ADC values and radscore with recurrence, and verified in the test group.ResultsADCmean showed inverse correlation with recurrence, while radscore was positively associated with recurrence. In univariate analyses, FIGO stage, pathological types, myometrial invasion, ADCmean, ADCmin and radscore were associated with recurrence. In the training group, multivariate Cox analysis showed that pathological types, ADCmean and radscore were independent risk factors for recurrence, which were verified in the test group.ConclusionsADCmean value and radscore were independent predictors of recurrence of EC, which can supplement prognostic information in addition to clinicopathological information and provide basis for individualized treatment and follow-up plan.

Clinicopathologic characteristics of patients with endometrial cancer and their treatment outcome in BPKMCH

Background: There are few studies on endometrial carcinoma in Nepal so present study aims to evaluate the clinicopathologic characteristics of endometrial cancer patients along with their treatment outcome.
 Material and Methods: This is a descriptive study conducted from January 2011 to December 2020 and all patients of endometrial carcinoma who had undergone primary surgery at B.P. Koirala Memorial Cancer Hospital were included. Socio-demographic characteristics, clinical presentations, histologic type, treatment modalities and outcomes were obtained and analyzed.
 Results: The mean age was found to be 58 8.32 years. Most were postmenopausal accounting for 86%. Medical co-morbidities were associated in 40% of patients. Most common presentation was postmenopausal bleeding seen in 68% of patients. Total abdominal hysterectomy and bilateral salpingo-oophorectomy was done in 48% of patients. The main histologic type was endometrioid carcinoma observed in 96% of patients. Low grade carcinoma was found in 78% of patients out of which grade 1 accounting for 50% and rest grade 2 while high grade carcinoma was found 22% of patients. 64% of patients required adjuvant therapy. Recurrence was seen in 16% of patients.
 Conclusions: Endometrial carcinoma is common in post menopausal age group. Endometrioid variety is the commonest histologic type. Clinicopathologic characters of endometrial carcinoma affect the prognosis of the patient.

Use of diffusion-weighted imaging and diffusion tensor imaging in assessment of myometrial invasion in patients of endometrial carcinoma and its correlation with histopathological grading (Prospective study)

BackgroundEndometrial cancer (EMC) is considered one of the most common gynecological cancers worldwide. In particular, the depth of myometrial invasion and histological grade of endometrial cancers (EMCs) are strong prognostic factors. Diffusion tensor measurements as mean diffusivity (MD) and fractional anisotropy (FA) values could be useful for assessing the depth of tumor invasion and its histological grade. The study aimed to evaluate the role of diffusion-weighted imaging (DWI) and diffusion tensor imaging in the detection of myometrial invasion in cases of endometrial carcinoma and prediction of its grade in vivo.ResultsThis study included 50 female patients with pathologically proved endometrial carcinoma, and their ages ranged from 38 to 67 years; the mean age was 56.15 years (± 8.229 standard deviation “SD”). There was a significant statistical difference regarding the mean values of diffusion tensor fractional anisotropy (DT-FA), diffusion tensor mean diffusivity (DT-MD) and diffusion-weighted apparent diffusion coefficient(DW-ADC) values in differentiating between intact and infiltrated myometrium with (P value ≤ 0.001). The accuracy of DT-MD, DT-FA and DWI-ADC was 98%, 90% and 86%, respectively, in the detection of myometrial invasion. There was a statistically significant difference in the mean values of DT-FA, DT-MD and DW-ADC for differentiating endometrioid adenocarcinoma grades with the overall P values (˂0.001). The accuracy of DT-FA, DT- MD and DWI-ADC for differentiating grade 3 from grade 1 or 2 endometrioid adenocarcinoma was 94.9%, 84.6% and 74.4%, respectively. For differentiating grade 1 from grade 2 or 3 endometrioid adenocarcinoma, the accuracy of DT-FA, DT-MD and DWI-ADC was 90%, 89.7% and 84.6%, respectively. Mean DT-FA, DT-MD and DW-ADC values were inversely proportional to the degree of pathological grading with r = − 0.867, − 0.762 and − 0.706, respectively.ConclusionDiffusion tensor imaging and DWI are helpful in the assessment of myometrial invasion and have a high negative correlation with histopathological grading in patients with endometrial cancer.

LncRNAs PSMG3-AS1 and MEG3 negatively regulate each other to participate in endometrial carcinoma cell proliferation.

Endometrial carcinoma (EC), also known as corpus cancer or corpus uterine cancer, is the most frequently diagnosed genital cancer among women in developed countries. Our preliminary RNA-seq analysis revealed the inverse correlation between the expression of PSMG3-AS1 and MEG3 across EC tissues, indicating the possible interaction between them. This study aimed to explore the interaction between two long non-coding RNAs (lncRNAs) PSMG3-AS1 and MEG3 in EC. Investigation of the interaction between two lncRNAs in cancer biology is a novel topic. The expression of PSMG3-AS1 and MEG3 in EC and paired non-tumor tissues from 60 EC patients were determined by RT-qPCR. Correlations between them were analyzed by Pearson's correlation coefficient. PSMG3-AS1 and MEG3 were overexpressed in EC cells to study the relationship between them. The roles of PSMG3-AS1 and MEG3 in regulating the proliferation of EC cells were assessed by CCK-8 assay. PSMG3-AS1 was upregulated, while MEG3 was downregulated in EC. Across EC tissues, the expression of PSMG3-AS1 and MEG3 were inversely correlated. In EC cells, overexpression of PSMG3-AS1 and MEG3 resulted in the downregulation of each other. In cell proliferation assay, PSMG3-AS1 promoted cell proliferation, and MEG3 inhibited cell proliferation. Moreover, the proliferation rate of cells co-transfected with PSMG3-AS1 and MEG3 expression vectors was not different from that in cells without transfections. In conclusion, PSMG3-AS1 and MEG3 may negatively regulate each other to regulate EC cell proliferation.

Nine Pyroptosis-Related lncRNAs are Identified as Biomarkers for Predicting the Prognosis and Immunotherapy of Endometrial Carcinoma.

BackgroundEndometrial carcinoma (EC) is one of the most common malignancies. Immunotherapy has shown promising effects in the treatment against specific subtypes of EC.MethodsThe RNA and clinical information of patients with EC were acquired from The Cancer Gene Atlas (TCGA) database. Firstly, the differentially expressed pyroptosis-related lncRNAs (PRLs) were screened between the tumor and normal control tissue. Secondly, the PRLs closely related to survival were identified by univariate and multivariate regression analysis, based on which, we evaluated the risk score for each EC patient to construct a risk signature. Moreover, we assessed the prognostic value, clinical relevance immunity, and immunotherapy based on this signature.ResultsWe screened out 9 individual PRLs (AC087491.1, AL353622.1, AL035530.2, LINC02036, AL021578.1, AL390195.2, AC009097.2, AC004585.1, and AC244517.7) closely related to the prognosis of EC. Kaplan–Meier analyses showed a poorer prognosis for the patients in the high-risk FRLs signature (P < 0.001). The area under the curve (AUC) for 1 year, 2 years, 3 years was 0.693, 0.694, 0.750, respectively. Our risk model could be considered as an independent prognostic marker for EC (P < 0.001, HR:2.172, 95% CI:1.532–3.079). Moreover, immune functions and checkpoints were generally different in the 2 groups. Simulation analysis by termed immunophenoscores hinted that immunotherapy might bring optimal therapeutic effect in the low-risk group.ConclusionWe successfully developed a novel signature with 9 lncRNAs related to pyroptosis, which may be used as biomarkers to evaluate the prognosis and immune treatment of EC.

Evaluation of Sentinel Lymph Node Sampling in Complex Atypical Hyperplasia

<h3>Study Objective</h3> Primary objective - to evaluate safety and efficacy of sentinel lymph node (SLN) sampling during robot assisted total laparoscopic hysterectomy and bilateral salpingo-oophorectomy (TLH/BSO) of patients with complex atypical hyperplasia (CAH). Secondary objective - to determine the risk of endometrial carcinoma in patients with preoperative diagnosis of CAH. <h3>Design</h3> Retrospective chart review performed from May 2012 to February 2020 of CAH patients who underwent TLH/BSO. Demographic data, operative data, histopathology, SLN ultra-staging data collected. Intra-operative and 30-day postoperative complications evaluated using Clavien-Dindo classification. <h3>Setting</h3> Single institution. <h3>Patients or Participants</h3> Inclusion criteria was preoperative diagnosis of CAH, ages 18-90, robotic assisted TLH/BSO. 74 charts reviewed 57 patients included. <h3>Interventions</h3> Of 57 patients, 25 patients underwent SLN sampling under near infra-red light after cervical injection of indocyanine green dye. 32 patients in control group that did not have lymph node sampling. <h3>Measurements and Main Results</h3> Two-sided t-test, Chi squared test and Fisher's exact test used in data analysis. The incidence of cancer was 32/57 (56.1%). Thirteen (52%) patients in SLN group had cancer vs 19 (59.4%) in the control group. The rate of deep (>50%) myometrial invasion in SLN group was 30.8% vs 5.3% in control group (P=0.05). The map rate of SLN was 100% (76% Bilateral, 24% Unilateral). Zero SLN sampled were positive for metastatic disease. 30-day complication rate in SLN group was 0% vs 6.3% in control group (P=0.5). Sixteen (28%) patients had borderline (bordering on carcinoma) pathology on preoperative sampling. Eight (50%) had SLN sampling. Twelve (75%) had a postoperative diagnosis of cancer. There were no identified preoperative risk factors for cancer. <h3>Conclusion</h3> The incidence of endometrial cancer in patients with preoperative diagnosis of CAH was 56%. Zero patients had metastatic disease to SLN. SLN dissection was not associated with more operative time or complications. Patients with a preoperative borderline pathology seem to have a higher risk of cancer.

Medical Significance of Uterine Corpus Endometrial Carcinoma Patients Infected With SARS-CoV-2 and Pharmacological Characteristics of Plumbagin.

BackgroundClinically, evidence shows that uterine corpus endometrial carcinoma (UCEC) patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may have a higher death-rate. However, current anti-UCEC/coronavirus disease 2019 (COVID-19) treatment is lacking. Plumbagin (PLB), a pharmacologically active alkaloid, is an emerging anti-cancer inhibitor. Accordingly, the current report was designed to identify and characterize the anti-UCEC function and mechanism of PLB in the treatment of patients infected with SARS-CoV-2 via integrated in silico analysis.MethodsThe clinical analyses of UCEC and COVID-19 in patients were conducted using online-accessible tools. Meanwhile, in silico methods including network pharmacology and biological molecular docking aimed to screen and characterize the anti-UCEC/COVID-19 functions, bio targets, and mechanisms of the action of PLB.ResultsThe bioinformatics data uncovered the clinical characteristics of UCEC patients infected with SARS-CoV-2, including specific genes, health risk, survival rate, and prognostic index. Network pharmacology findings disclosed that PLB-exerted anti-UCEC/COVID-19 effects were achieved through anti-proliferation, inducing cytotoxicity and apoptosis, anti-inflammation, immunomodulation, and modulation of some of the key molecular pathways associated with anti-inflammatory and immunomodulating actions. Following molecular docking analysis, in silico investigation helped identify the anti-UCEC/COVID-19 pharmacological bio targets of PLB, including mitogen-activated protein kinase 3 (MAPK3), tumor necrosis factor (TNF), and urokinase-type plasminogen activator (PLAU).ConclusionsBased on the present bioinformatic and in silico findings, the clinical characterization of UCEC/COVID-19 patients was revealed. The candidate, core bio targets, and molecular pathways of PLB action in the potential treatment of UCEC/COVID-19 were identified accordingly.

Evaluation of the Depth of Myometrial Invasion of Endometrial Carcinoma: Comparison of Orthogonal Pelvis-axial Contrast-enhanced and Uterus-axial Dynamic Contrast-enhanced MRI Protocols

To compare the diagnostic performance of orthogonal pelvis-axial (OPA) contrast-enhanced (CE) and orthogonal uterus-axial (OUA) dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) protocols in assessing the depth of myometrial invasion (MI) of endometrial carcinoma (EC). Preoperative MRI of 398 consecutive EC patients (197 patients with OPA CE-MRI protocol and 201 patients with OUA DCE-MRI protocol) was analyzed. Two radiologists independently interpreted the depth of MI, with postoperative histopathology as the reference standard. The chi-square test, Fisher's exact test, and receiver operating characteristic curve analysis were used for diagnostic performance comparison. OUA DCE-MRI showed a significantly larger area under the curve than OPA CE-MRI in detecting the presence of MI for radiologist 1 (0.71 versus 0.49, p < 0.05) but not for radiologist 2 or deep MI (all p > 0.05). Compared to OPA CE-MRI, OUA DCE-MRI significantly improved the diagnostic accuracy of non-MI and superficial MI (radiologist 1: 45.5% versus 0 and 88.7% versus 86.4%, p=0.045 and 0.567, respectively; radiologist 2: 45.5% versus 12.5% and 88.7% versus 78.8%, p=0.177 and 0.027, respectively) and of EC with adenomyosis/submucous myomas, cornual tumor, and antero-posterior diameter ≤ 10 mm (radiologist 1: 86.4% versus 71.4%, 91.2% versus 67.7%, and 90.1% versus 81.1%, p=0.048, 0.018, and 0.081, respectively; radiologist 2: 86.4% versus 64.3%, 88.2% versus 64.5%, and 87.0% versus 71.6%, p=0.006, 0.023, and 0.019, respectively). The OUA DCE-MRI protocol was superior to the OPA CE-MRI protocol in assessing the depth of MI of EC.

Mechanical Stimulus-Related Risk Signature Plays a Key Role in the Prognostic Nomogram For Endometrial Cancer.

BackgroundTumor biomechanics correlates with the progression and prognosis of endometrial carcinoma (EC). The objective of this study is to construct a risk model using the mechanical stimulus-related genes in EC.MethodsWe retrieved the transcriptome profiling and clinical data of EC from The Cancer Genome Atlas (TCGA) and Molecular Signatures Database (MSigDB). Differentially expressed mechanical stimulus-related genes were extracted from the databases, and then the least absolute shrinkage and selection operator (LASSO) regression analysis was used to construct a risk model. A nomogram integrating the genes and the clinicopathological characteristics was established and validated using the Kaplan-Meier survival and receiver operating characteristic (ROC) curves to estimate the overall survival (OS) of EC patients. Protein profiling technology and immunofluorescence technique were performed to verify the connection between biomechanics and EC.ResultsIn total, 79 mechanical stimulus-related genes were identified by analyzing the two databases. Based on the LASSO regression analysis, 7 genes were selected for the establishment of the risk model. This model showed a good performance in terms of the prognostic accuracy in high- and low-risk groups. The area under the ROC curves (AUC) of this model was 0.697, 0.712 and 0.723 for 3-, 5- and 7-year OS, respectively. Then, a nomogram integrating the genes of the risk model and clinical features was constructed. The nomogram could accurately predict the OS (AUC = 0.779, 0.812 and 0.806 for 3-, 5- and 7-year OS, respectively). The results of the protein profiling technology and immunofluorescence revealed the expression of cytoskeleton proteins to be correlated with the Matrigel stiffness degree.ConclusionsIn summary, a risk model of 7 mechanical stimulus-related genes was identified in EC. A nomogram based on this risk model and combining the clinicopathological features to assess the overall survival of EC showed high practical value.

Livin/BIRC7 gene expression as a possible diagnostic biomarker for endometrial hyperplasia and carcinoma

BackgroundLivin/BIRC7 is a member of the inhibitors of apoptosis proteins family which are implicated in development of cancer through the inhibition of apoptosis process. This case-control study was intended to investigate livin/BIRC7 gene expression in endometrial hyperplasia and carcinoma and its correlation to some oxidative stress markers in addition to its possible diagnostic performance. MethodsThis study included 90 participants [30 endometrial hyperplasia patients, 30 endometrial carcinoma patients, and 30 healthy controls]. Livin/BIRC7 gene expression was analyzed using quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). Serum catalase activity was assessed by enzyme-linked immunosorbent assay (ELISA) and malondialdehyde level was measured by the colorimetric method. ResultsLivin/BIRC7 gene expression was significantly (p < 0.001) higher in endometrial carcinoma from patients with endometrial hyperplasia when compared to controls. A positive correlation was found between livin/BIRC7 expression and serum catalase activity and malondialdehyde level in endometrial hyperplasia and carcinoma. The detection of livin/BIRC7 in endometrial carcinoma has excellent sensitivity and specificity. ConclusionsLivin/BIRC7 was overexpressed in endometrial carcinoma with excellent power to differentiate endometrial carcinoma from endometrial hyperplasia or healthy subjects, suggesting that it might be a useful molecular marker for endometrial carcinoma diagnosis.

Identification of the Ferroptosis-Associated Gene Signature to Predict the Prognostic Status of Endometrial Carcinoma Patients.

Endometrial carcinoma (EC) is one of the most common gynecological carcinomas. As previously described, ferroptosis was reported to exhibit a significant association with the development of malignant neoplasms. Nevertheless, there are few studies towards the association between the implication of ferroptosis-related genes (FRGs) and the prognostic status of patients with EC. Our study demonstrated that ferroptosis-related genes were evidently differently expressed in EC. Further analysis showed that SLC7A11, SAT1, CDKN1A, and TP5MC3 expression was linked to the low stage, grade of pTNM, and longer survival time. Bioinformatics analysis demonstrated that these ferroptosis-related regulators played a crucial role in EC by modulating multiple biological processes, such as cell cycle, citrate cycle (TCA cycle), metabolism-related pathways, ERK activation, p53 signaling pathway, cellular senescence, TAp63 pathway, and Notch signaling pathway. Of note, our results showed that ATP5MC3, CDKN1A, and SLC7A11 expression was dramatically positively related with the tumor mutational burden (TMB) score in EC. However, we did not observe a significant correlation between SAT1 and the TMB score in EC. These findings for the first time demonstrated that ferroptosis was displayed crucially in EC progression. We speculated that our findings offered novel targets and strategies for personalized treatment.

Application of vaginoscopy in the diagnosis and treatment of occult vaginal high-grade squamous intraepithelial lesions

Objective: To investigate the application value of vaginoscopy in the diagnosis and treatment of vaginal squamous intraepithelial lesions post hysterectomy. Methods: From May 2017 to June 2020, patients with high-risk (HR)-HPV infection and (or) cytological abnormalities after hysterectomy in Obstetrics and Gynecology Hospital Affiliated to Fudan University were examined by colposcopy, and those who were not satisfied with exposure under colposcopy were further examined by vaginoscopy. The role of vaginoscopy in the detection and treatment of occult vaginal squamous intraepithelial lesions was analyzed. Results: A total of 153 patients with HR-HPV infection and (or) cytological abnormalities, and inadequate colposcopy were enrolled in this study. The average age was (49.8±8.1) years. All cases were successfully performed vaginoscopy with no vaginal perforation, no bladder and intestinal injury. During vaginoscopy, 11 (7.2%, 11/153) cases with unclear high-grade squamous intraepithelial lesion (HSIL) boundary under colposcopy were found with clear HSIL boundary, and new HSIL was found in 23 (15.0%, 23/153) cases. According to colposcopy, there were 89 cases of normal or inflammation, 45 cases of vaginal low-grade squamous intraepithelial lesion (LSIL) and 19 cases of vaginal HSIL. According to vaginoscopy, there were 56 cases of normal or chronic inflammation, 55 cases of vaginal LSIL, 40 cases of vaginal HSIL (including 2 cases of vaginal HSIL could not exclude cancer) and 2 cases of vaginal carcinoma. There were significant difference between colposcopy and vaginoscopy (P<0.01). The missed diagnosis rate of vaginal apex blind curettage under colposcopy was 54.8%. For the 40 cases with vaginal HSIL under vaginoscopy, 15 cases were completely curettaged with vaginal endoscopic claw forceps, and 22 cases were vaporized by Versapoint. Among the 37 cases of vaginal HSIL treated by vaginoscopy, 34 cases were followed up for 6 months with 31 cases of vaginal HSIL cured. The cure rate was 91.2% (31/34), the positive rate of HR-HPV decreased from 100.0% (34/34) to 79.4% (27/34). Conclusion: For patients with inadequate exposure of vaginal apex during colposcopy posthysterectomy, vaginoscopy is helpful to detect the occult lesions in the vaginal apex, and it could also be used for the treatment of vaginal squamous intraepithelial lesions.

Improving preoperative diagnosis in endometrial cancer using systematic morphological assessment and a small immunohistochemical panel

Preoperative histopathological classification determines the primary surgical approach in endometrial carcinoma (EC) patients but has only moderate agreement between preoperative and postoperative diagnosis. The aim of the PIpelle Prospective ENDOmetrial carcinoma (PIPENDO) study is to determine whether histopathological assessment and a small panel of diagnostic biomarkers decreases discrepancies between preoperative and postoperative diagnosis in EC. Preoperative endometrial tissue of 378 included patients with EC was stained with 15 different antibodies. Clinically relevant discrepancies in grade or histological subtype between original preoperative and reviewed postoperative diagnosis were observed in 75 (20%) patients. Highest clinically relevant discrepancy was found in grade 2ECs (20%), compared to 5% and 14% in respectively grade 1 and 3 endometrioid endometrial carcinomas (EECs). A practical two-biomarker panel with PR and p53 improved diagnostic accuracy (AUC=0.92; 95%CI=0.88-0.95) compared to solely morphological evaluation (AUC=0.86). In preoperative high-grade EC, the diagnostic accuracy of histological subtype was improved by a three-immunohistochemical biomarker panel (PR, IMP3, and L1CAM) (AUC=0.93; 95%CI=0.88-0.98) compared to solely morphological evaluation (AUC=0.81). In conclusion to improve correct preoperative diagnosis in EC, we recommend use of a panel of at least two easily accessible immunohistochemical biomarkers (PR and p53), only in grade 2ECs. Overall, this will reduce clinically relevant discrepancies in tumor grade and subtype with postoperative diagnosis with 6% (from 20% to 14%). Addition of PR, IMP3, and L1CAM for histological subtyping in high-grade EECs resulted in a further decrease in discrepancies with 8% (from 20% to 12%).

Comprehensive Clinicopathologic Analysis for Mismatch Repair Protein Expression in Unselected Endometrial Carcinoma Patients With an Emphasis on the Role of MLH1 Deficiency.

Screening for mismatch repair (MMR) deficiency in unselected patients with endometrial carcinoma (EC) and the clinicopathologic descriptions of ECs with MMR deficiency have been well demonstrated in Western populations, but studies on Asian populations are relatively scarce. In this study, we described the clinicopathologic features of ECs according to MMR status in unselected Taiwanese patients. We also conducted subgroup analysis of MMR-deficient (dMMR) cases according to the presence or absence of MLH1. Patients diagnosed with ECs between January 2017 and February 2020 at our institution were included. Immunohistochemistry analysis of MLH1, PMS2, MSH2, and MSH6 proteins on endometrial primary tumors and clinicopathologic variables were assessed retrospectively. A total of 231 EC patients were enrolled, of whom 50 (21.6%) had dMMR tumors. Of these 50 cases, 39 had tumors that lacked MLH1 expression and 11 were positive for MLH1. The overall dMMR group was significantly related to older age, parity, and high histologic grade compared with the MMR-proficient (pMMR) group. ECs with MLH1 deficiency were obviously associated with several poor pathologic features, including high histologic grade, lymph node metastasis, and lymphovascular space invasion. Moreover, we first reported that parity and the late age at menopause are strongly correlated with MLH1-related dMMR EC group compared with pMMR group. In conclusion, triaging EC patients into pMMR, MLH1-related dMMR and non-MLH1-related dMMR groups by immunohistochemistry analysis may help clinicians to predict disease behavior and guide further management. The strong association between parity and MLH1-related dMMR ECs warrants further investigation on the underlying mechanism.

Prognosis-associated methylation subtypes in endometrial carcinoma patients and the role of magnetic nanoparticles in gene extraction

Endometrial cancer is one of the most common gynecological malignancies, and DNA methylation plays a vital role in its occurrence and development. In this study, we collected the relevant data on endometrial cancer from the Cancer Genome Atlas database and UCSC website. By screening and processing the data, we obtained 410 samples and 16,381 methylation sites. Endometrial carcinoma can be divided into seven molecular subtypes using consensus clustering method. Based on the analysis of the differences among subtypes, the methylation degree of different sites was obtained, and the prognosis model of methylation sites was established. Based on the median value of the train group, the train and test groups were divided into high and low-risk groups. The survival between the high and low-risk groups was different. It also showed that this model can predict the survival of patients, with better accuracy. In conclusion, the tumor subtypes based on methylation sites can provide a better guidance for treatment, relapse, and prognosis of endometrial cancer. In this study, magnetic nanoparticles can be used to extract genomic DNA and total RNA due to their paramagnetism and biocompatibility, then transcriptome high-throughput sequencing was performed. It may serve as potential cancer immune biomarker targets for developing future oncological treatments.

Prognostic and clinicopathological significance of TMEFF2, SMOC-2, and SOX17 expression in endometrial carcinoma

Backgroundthere is a need for novel biomarkers and targeting therapies for predicting Endometrial carcinoma (EC) progression and recurrence. TMEFF2 is a gene that was found to play a role in EMT. SMOC-2 is expressed in embryogenesis and it was identified as a recent stem cell-related gene that has a role in cancer progression. SRY-box 17 (SOX17) is a member of the SRY-related HMG-box (SOX) family of transcription factors. Dysregulation or downregulation of SOX17 expression was found in many cancer tissues.Aim: In the present study, we aimed to assess the tissue protein expressions of TMEFF2, SMOC-2, and SOX17 in EC using immunohistochemistry to evaluate their clinicopathological values and prognostic roles in EC patients.PATIENTS AND METHODS: This is prospective cohort study included 120 patients with EC. Sections from 120 paraffin blocks were retrieved and stained with TMEFF2, SMOC-2, and SOX17 using immunohistochemistry, the expression of markers in all tissue samples was assessed, analyzed and correlation of pathological parameters with the levels of expression was done. All patients were followed up till death or till the last known alive data for about 50 months (range from 25 to 60).RESULTS: TMEFF2, SMOC-2 expression was correlated with the presence of lymph node metastases (p = 0.023), distant metastasis (p = 0.039) recurrence of the tumor after successful therapy, overall survival, and disease-free survival (p < 0.001). SOX17 positive expression was positively correlated with low grade (p = 0.019), absence of lymph node metastasis (p = 0.001), absence of distant metastasis (p = 0.013), low stage (p = 0.03), and its negative expression was positively correlated with recurrence of the tumor after successful therapy, overall survival and disease-free survival (p = 0.001).In conclusion, we demonstrated that both TMEFF2 and SMOC-2 were highly expressed in EC and were associated with a shortened survival rate, dismal outcome, and poor prognosis in EC patients. While SOX17 expression was related to a favorable outcome and its down-regulation was associated with dismal EC patient's survival.

LncRNA OIP5-AS1 Suppresses Cell Proliferation and Invasion of Endometrial Cancer by Regulating PTEN/AKT via Sponging miR-200c-3p.

Background Endometrial carcinoma (EC) is one of the major gynecologic malignancy cancers affecting females with dismal prognosis and high mortality around the world. Numerous studies have proven that an aberrant level of long noncoding RNAs is present in many endometrial cancer patients, while the underlying molecular mechanism remains unclear. Method The expression levels of lncRNA OIP5-AS1, miR200c-3p, and PTEN were measured by a quantitative real-time polymerase chain reaction in endometrial cancer tissue and endometrial cancer cells. CCK8 assay, wound-healing assay, and cell colony formation were applied to evaluate cell proliferation, cell migration, and cell colony formation ability. Cell cycle and cell apoptosis were detected by flow cytometry. The interactions between OIP5-AS1, miR200c-3p, and PTEN were explored by luciferase activity. Results In the present study, we demonstrated that long noncoding RNA OIP5-AS1 was significantly reduced in EC tissue compared with normal tissue. The lower expression level of OIP5-AS1 was also confirmed in four kinds of EC cell lines compared with the normal endometrial cell line. Gain- and loss-of-function of experiments indicated that upregulation of OIP5-AS1 could inhibit the proliferation, migration, and invasion of EC cells in vitro. Meanwhile, overexpression of OIP5-AS1 could also suppress the growth of tumor in the xenograft model. Moreover, further study revealed that miR-200c-3p could bind to OIP5-AS1, and the loss function of miR-200c-3p could reverse the elevated OIP5-AS1's inhibitory effect on the progression of EC. Furthermore, we found that downregulation of miR-200c-3p was inversely correlated with PTEN expression in EC cells. Reduced OIP5-AS1 could lead to the accumulation of miR-200c-3p, which could induce the upregulation of PTEN indirectly. Conclusion Our study demonstrated a novel molecular mechanism that lncRNA OIP5-AS1 could modulate the progression of EC by combining competitively with miR-200c-3p to control the PTEN/AKT pathway in EC cells, which might supply important information for developing novel therapeutic strategies for EC patients.

Nomograms of Combining Apparent Diffusion Coefficient Value and Radiomics for Preoperative Risk Evaluation in Endometrial Carcinoma

ObjectivesTo evaluate the value of nomogram models combining apparent diffusion coefficient (ADC) value and radiomic features on magnetic resonance imaging (MRI) in predicting the type, grade, deep myometrial invasion (DMI), lymphovascular space invasion (LVSI), and lymph node metastasis (LNM) of endometrial carcinoma (EC) preoperatively.MethodsThis study included 210 EC patients. ADC value was calculated, and radiomic features were measured on T2-weighted images. The univariate and multivariate logistic regressions and cross-validations were performed to reduce valueless features, then radiomics signatures were developed. Nomogram models using ADC combined with radiomic features were developed in the training cohort. The receiver operating characteristic (ROC) curve was performed to estimate the diagnostic efficiency of nomogram models by the area under the curve (AUC) in the training and validation cohorts.ResultsThe ADC value was significantly different between each subgroup. Radiomic features were ultimately limited to four features for type, six features for grade, six features for DMI, four features for LVSI, and eight features for LNM for the nomogram models. The AUC of the nomogram model combining ADC value and radiomic features in the training and validation cohorts was 0.851 and 0.867 for type, 0.959 and 0.880 for grade, 0.839 and 0.766 for DMI, 0.816 and 0.746 for LVSI, and 0.910 and 0.897 for LNM.ConclusionsThe nomogram models of ADC value combined with radiomic features were associated with the type, grade, DMI, LVSI, and LNM of EC, and provide an effective, non-invasive method to evaluate preoperative risk stratification for EC.

Impact of adenomyosis on the prognosis of patients with endometrial cancer.

BackgroundDespite the high prevalence of adenomyosis in hysterectomy specimens of endometrial carcinoma (EC) patients, the relationship between adenomyosis and EC prognosis appears unclear.ObjectiveTo assess the prognostic value of coexistent adenomyosis in patients with EC.MethodsA systematic review and meta‐analysis was performed by searching six electronic databases for studies reporting data on prognosis of EC patients with and without coexistent adenomyosis. Studies with patient selection based on prognostic factors were excluded. Pooled univariate hazard ratio (HR) analyses for overall survival (OS) and disease‐free survival (DRF) were performed, using EC patients without adenomyosis as a control group. For DFS, pooled multivariate HR analysis was also evaluable.ResultsThree studies of 2505 EC patients (553 with and 1952 without adenomyosis) were included. Compared with EC patients without adenomyosis, EC patients with coexistent adenomyosis showed a pooled HR of 0.533 (CI 95%, 0.329–0.864) for OS at univariate analysis; 0.536 (CI 95%, 0.334–0.859) for DFS at univariate analysis; and 0.875 (CI 95%, 0.331–2.315) for DFS at multivariate analysis.ConclusionIn EC patients with coexistent adenomyosis, the risk of death is halved compared with EC patients without adenomyosis. However, the independence of this association needs to be verified in future studies.

Integrative Analysis of Differently Expressed Genes Reveals a 17-Gene Prognosis Signature for Endometrial Carcinoma.

Endometrial carcinoma (EC) is the fifth widely occurring malignant neoplasm among women all over the world. However, there is still lacking efficacy indicators for EC's prognosis. Here, we analyzed two databases including an RNA-sequencing-based TCGA dataset and a microarray-based GSE106191. After normalizing the raw data, we identified 114 common genes with upregulation and 308 common genes with downregulation in both the TCGA and GSE106191 databases. Bioinformatics analysis showed that the differently expressed genes in EC were related to the IL17 signaling pathway, PI3K-Akt signaling pathway, and cGMP-PKG signaling pathway. Furthermore, we performed the least absolute shrinkage and selection operator (LASSO) Cox regression analysis and generated a signature featuring 17 prognosis-related genes (MAL2, ANKRD22, METTL7B, IL32, ERFE, OAS1, TRPC1, SRPX, RAPGEF4, PSD3, SIMC1, TRPC6, WFS1, PGR, PAMR1, KCNK6, and FAM189A2) and found that it could predict OS in EC patients. The further analysis showed that OAS1, MAL2, ANKRD22, METTL7B, and IL32 were significantly upregulated in EC samples after comparison with normal samples. However, TRPC1, SRPX, RAPGEF4, PSD3, SIMC1, TRPC6, WFS1, PGR, PAMR1, KCNK6, and FAM189A2 were significantly downregulated in EC samples in comparison with normal samples. And correlation analysis showed that our results showed that the expressions of 17 prognosis-related hub genes were significantly correlated based on Pearson correlation. We here offer a newly genetic biomarker for the prediction of EC patients' prognosis.