Magnetic resonance imaging-based radiomics model for preoperative assessment of risk stratification in endometrial cancer

BACKGROUND Preoperative risk stratification is significant for the management of endometrial cancer(EC)patients.Radiomics based on magnetic resonance imaging(MRI)in combination with clinical features may be useful to predict the risk grade of EC.AIM To construct machine learning models to predict preoperative risk stratification of patients with EC based on radiomics features extracted from MRI.METHODS The study comprised 112 EC patients.The participants were randomly separated into training and validation groups with a 7:3 ratio.Logistic regression analysis was applied to uncover independent clinical predictors.These predictors were then used to create a clinical nomogram.Extracted radiomics features from the T2-weighted imaging and diffusion weighted imaging sequences of MRI images,the Mann-Whitney U test,Pearson test,and least absolute shrinkage and selection operator analysis were employed to evaluate the relevant radiomic features,which were subsequently utilized to generate a radiomic signature.Seven machine learning strategies were used to construct radiomic models that relied on the screening features.The logistic regression method was used to construct a composite nomogram that incorporated both the radiomic signature and clinical independent risk indicators.RESULTS Having an accuracy of 0.82 along with an area under the curve(AUC)of 0.915[95%confidence interval(CI):0.806-0.986],the random forest method trained on radiomics characteristics performed better than expected.The predictive accuracy of radiomics prediction models surpassed that of both the clinical nomogram(AUC:0.75,95%CI:0.611-0.899)and the combined nomogram(AUC:0.869,95%CI:0.702-0.986)that integrated clinical parameters and radiomic signature.CONCLUSION The MRI-based radiomics model may be an effective tool for preoperative risk grade prediction in EC patients.

circRNA3669 promotes goat endometrial epithelial cells proliferation via miR-26a/RCN2 to activate PI3K/AKT-mTOR and MAPK pathways

The development of receptive endometrium(RE) from pre-receptive endometrium(PE) for successful embryo implantation is a complex dynamic process in which the morphology and physiological states of the endometrial epithelium undergo a series of significant changes, including cell proliferation and apoptosis. However, the molecular mechanisms are not yet fully understood. In this study, a higher circRNA3669 level was observed in PE than in RE of goats. Functional assays revealed that this overexpression promoted the proliferation of goat endometrial epithelial cells(GEECs) by activating the expression of genes related to the PI3K/AKT-mTOR and MAPK pathways,thereby inhibiting apoptosis in vitro. Furthermore, circRNA3669 functioned as a competing endogenous RNA(ceRNA) to upregulate Reticulocalbin-2(RCN2) expression at the post-transcriptional level by interacting with and downregulating miR-26a in GEECs. In addition, RCN2, which is highly expressed in the PE of goats, was found to be regulated by β-estradiol(E2) and progesterone(P4). Our results demonstrated that RCN2 also affected the key proteins PI3K, AKT, mTOR, JNK, and P38 in the PI3K/AKT-mTOR and MAPK pathways, thereby facilitating GEECs proliferation and suppressing their apoptosis in vitro. Collectively, we constructed a new circRNA3669-miR-26aRCN2 regulatory network in GEECs, which further provides strong evidence that circRNA could potentially play a crucial regulatory role in the development of RE in goats.

Antitumor Effect of Apcin on Endometrial Carcinoma via p21-Mediated Cell Cycle Arrest and Apoptosis

Objective Endometrial carcinoma(EC)is a prevalent gynecological malignancy characterized by increasing incidence and mortality rates.This underscores the critical need for novel therapeutic targets.One such potential target is cell division cycle 20(CDC20),which has been implicated in oncogenesis.This study investigated the effect of the CDC20 inhibitor Apcin on EC and elucidated the underlying mechanism involved.Methods The effects of Apcin on EC cell proliferation,apoptosis,and the cell cycle were evaluated using CCK8 assays and flow cytometry.RNA sequencing(RNA-seq)was subsequently conducted to explore the underlying molecular mechanism,and Western blotting and coimmunoprecipitation were subsequently performed to validate the results.Animal studies were performed to evaluate the antitumor effects in vivo.Bioinformatics analysis was also conducted to identify CDC20 as a potential therapeutic target in EC.Results Treatment with Apcin inhibited proliferation and induced apoptosis in EC cells,resulting in cell cycle arrest.Pathways associated with apoptosis and the cell cycle were activated following treatment with Apcin.Notably,Apcin treatment led to the upregulation of the cell cycle regulator p21,which was verified to interact with CDC20 and consequently decrease the expression of downstream cyclins in EC cells.In vivo experiments confirmed that Apcin treatment significantly impeded tumor growth.Higher CDC20 expression was observed in EC tissue than in nonmalignant tissue,and increased CDC20 expression in EC patients was associated with shorter overall survival and progress free interval.Conclusion CDC20 is a novel molecular target in EC,and Apcin could be developed as a candidate antitumor drug for EC treatment.

Development and validation of a circulating tumor DNA-based optimization-prediction model for short-term postoperative recurrence of endometrial cancer

BACKGROUND Endometrial cancer(EC)is a common gynecological malignancy that typically requires prompt surgical intervention;however,the advantage of surgical management is limited by the high postoperative recurrence rates and adverse outcomes.Previous studies have highlighted the prognostic potential of circulating tumor DNA(ctDNA)monitoring for minimal residual disease in patients with EC.AIM To develop and validate an optimized ctDNA-based model for predicting shortterm postoperative EC recurrence.METHODS We retrospectively analyzed 294 EC patients treated surgically from 2015-2019 to devise a short-term recurrence prediction model,which was validated on 143 EC patients operated between 2020 and 2021.Prognostic factors were identified using univariate Cox,Lasso,and multivariate Cox regressions.A nomogram was created to predict the 1,1.5,and 2-year recurrence-free survival(RFS).Model performance was assessed via receiver operating characteristic(ROC),calibration,and decision curve analyses(DCA),leading to a recurrence risk stratification system.RESULTS Based on the regression analysis and the nomogram created,patients with postoperative ctDNA-negativity,postoperative carcinoembryonic antigen 125(CA125)levels of<19 U/mL,and grade G1 tumors had improved RFS after surgery.The nomogram’s efficacy for recurrence prediction was confirmed through ROC analysis,calibration curves,and DCA methods,highlighting its high accuracy and clinical utility.Furthermore,using the nomogram,the patients were successfully classified into three risk subgroups.CONCLUSION The nomogram accurately predicted RFS after EC surgery at 1,1.5,and 2 years.This model will help clinicians personalize treatments,stratify risks,and enhance clinical outcomes for patients with EC.

Megestrol acetate plus metformin for fertility-sparing treatment of atypical endometrial hyperplasia and early-stage endometrial adenocarcinoma: a prospective study

Objective To evaluate the efficacy of medroxyprogesterone acetate(MA)plus metformin as the primary fertility-sparing treatment for atypical endometrial hyperplasia(AEH)and early-stage grade 1 endometrial adenocarcinoma(G1 EAC)and the recurrence rate after treatment.Methods Sixty patients(aged 20-42 years)with AEH and/or grade 1 EAC limited to the endometrium were enrolled prospectively and randomized into two groups(n=30)to receive oral MA treatment at the daily dose of 160 mg(control)or MA plus oral metformin(850 mg,twice a day)for at least 6 months.The treatment could extend to 12 months until a complete response(CR)was achieved,and follow-up hysteroscopy and curettage were performed every 3 months.For all the patients who achieved CR,endometrial expressions of IGFBP-rP1,p-Akt and p-AMPK were detected immunohistochemically.Results A total of 58 patients completed the treatment.After 9 months of treatment,23(76.7%)patients in the combined treatment group and 20(71.4%)in the control group achieved CR;two patients in the control group achieved CR after converting to the combined treatment.The recurrence rate did not differ significantly between the control group and combined treatment group(30.0%vs 22.7%,P>0.05).Ten(35.7%)patients in the control group experienced significant weight gain of 5.7±6.1 kg,while none of the patients receiving the combined treatment exhibited significant body weight changes.Compared with the control group,the patients receiving the combined treatment showed enhanced endometrial expressions of IGFBP-rP1 and p-AMPK with lowered p-Akt expression.Conclusion Metformin combined with MA may provide an effective option for fertility-sparing treatment of AEH and grade 1 stage IA EAC,and the clinical benefits of metformin for controlling MA-induced weight gain and promoting endometrial expressions of IGFBP-rP1 and p-AMPK while inhibiting p-Akt expression warrants further study.

Decoding exercise-induced atomic components and prognostic shifts in endometrial carcinoma through differentially expressed genes

Background:This study aimed to portray the atomic intelligence and prognostic implications of differentially expressed genes and their involvement in biological pathways in endometrial carcinoma,with a specific focus on the impacts of exercise on cancer.Methods:We utilized a multi-faceted approach,including volcano plots,Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses,Venn diagrams,protein-protein interaction networks,Kaplan-Meier survival analysis,Gene Set Variety Analysis,and single-cell transcriptomic analysis.Furthermore,we profiled tumor mutational scenes,assessed the prognostic value of immune-related features,and conducted a comprehensive examination of genetic variations and their impact on tumor mutational burden across different cancer types.Multidimensional genomic interactions and methylation elements were also investigated.Using real-time quantitative PCR and immunofluorescence staining,the effects of B-cell lymphoma 2(BCL2)silencing on TNF-αand caspase-3 gene expression were evaluated.Results:Our study identified a noteworthy number of differentially expressed genes in endometrial carcinoma with potential links to athletic performance traits.BCL2 expression levels were found to be associated with survival outcomes,and its changeability across cancers was related to immune cell infiltration and immune checkpoint gene expression.Single-cell investigations uncovered cellular complexity within tumor microenvironments and critical biological pathways in BCL2-overexpressing cells.The expression flow and mutational effect of BCL2 in endometrial carcinoma were characterized,and the prognostic implications of immune-related features were assessed.Hereditary variations,including copy number variations and their relationship with gene expression and tumor mutational burden,were investigated.Multidimensional genomic transaction highlighted the essential role of regulatory genes in cancer pathogenesis.Silencing of the BCL2 gene significantly inhibited the proliferation of HEC-108 cells and promoted apoptosis,as evidenced by decreased TNF-αgene expression and increased caspase-3 gene expression.Immunofluorescence staining further confirmed these results.Conclusion:This study gives a point-by-point understanding of the atomic intelligence and prognostic implications in endometrial carcinoma and across various other cancers.BCL2’s role as a modulatory factor within the tumor-resistant environment and its potential impact on disease prognosis and response to immunotherapy were underscored.The multidimensional genomic analysis provides insights into the complex interaction between genetic and epigenetic variables in cancer,which may shed light on future therapeutic strategies.This study indicates that silencing the BCL2 gene can significantly inhibit tumor cell proliferation and promote apoptosis through the regulation of the TNF-αand caspase-3 pathways.

ZNF554 Inhibits Endometrial Cancer Progression via Regulating RBM5 and Inactivating WNT/β-Catenin Signaling Pathway

Objective:Uterine corpus endometrial carcinoma(UCEC),a kind of gynecologic malignancy,poses a significant risk to women’s health.The precise mechanism underlying the development of UCEC remains elusive.Zinc finger protein 554(ZNF554),a member of the Krüppel-associated box domain zinc finger protein superfamily,was reported to be dysregulated in various illnesses,including malignant tumors.This study aimed to examine the involvement of ZNF554 in the development of UCEC.Methods:The expression of ZNF554 in UCEC tissues and cell lines were examined by qRT-PCR and Western blot assay.Cells with stably overexpressed or knocked-down ZNF554 were established through lentivirus infection.CCK-8,wound healing,and Transwell invasion assays were employed to assess cell proliferation,migration,and invasion.Propidium iodide(PI)staining combined with fluorescence-activated cell sorting(FACS)flow cytometer was utilized to detect cell cycle distribution.qRT-PCR and Western blotting were conducted to examine relative mRNA and protein levels.Chromatin immunoprecipitation assay and luciferase reporter assay were used to explore the regulatory role of ZNF554 in RNA binding motif 5(RBM5).Results:The expression of ZNF554 was found to be reduced in both UCEC samples and cell lines.Decreased expression of ZNF554 was associated with higher tumor stage,decreased overall survival,and reduced disease-free survival in UCEC.ZNF554 overexpression suppressed cell proliferation,migration,and invasion,while also inducing cell cycle arrest.In contrast,a decrease in ZNF554 expression resulted in the opposite effect.Mechanistically,ZNF554 transcriptionally regulated RBM5,leading to the deactivation of the Wingless(WNT)/β-catenin signaling pathway.Moreover,the findings from rescue studies demonstrated that the inhibition of RBM5 negated the impact of ZNF554 overexpression onβ-catenin and p-glycogen synthase kinase-3β(p-GSK-3β).Similarly,the deliberate activation of RBM5 reduced the increase inβ-catenin and p-GSK-3βcaused by the suppression of ZNF554.In vitro experiments showed that ZNF554 overexpression-induced decreases in cell proliferation and migration were counteracted by RBM5 knockdown.Additionally,when RBM5 was overexpressed,it hindered the improvements in cell proliferation and migration caused by reducing the ZNF554 levels.Conclusion:ZNF554 functions as a tumor suppressor in UCEC.Furthermore,ZNF554 regulates UCEC progression through the RBM5/WNT/β-catenin signaling pathway.ZNF554 shows a promise as both a prognostic biomarker and a therapeutic target for UCEC.

Endometrial carcinoma with cervical stromal invasion:Three case reports

BACKGROUND Endometrial cancer is a kind of well-known tumors of female genitourinary system.Cervical stromal invasion is an adverse factor for poor prognosis of endometrial cancer.There is still controversy regarding the use of magnetic resonance imaging(MRI)in the diagnosis of cervical stromal invasion of endometrial cancer.The diagnosis of cervical stromal invasion varies significantly between different observers and institutions.We present a limited case series of the particular pattern of endometrial cancer,which infiltrates the cervical stroma and is often overlooked.CASE SUMMARY We present three cases of endometrial carcinoma with cervical stromal invasion with cancer-free uterine cavity.One patient,a reproductive-aged woman,exhibited irregular menstruation and was diagnosed with endometrial polyps by hysteroscopy and segmental curettage.A MRI scan revealed polypoid nodules within the internal cervical orifice.The other two cases were postmenopausal women who presented with abnormal vaginal bleeding.Hysteroscopy and segmental curettage suggested atypical hyperplasia of the endometrium.MRI scans did not detect any malignant signs in the endometrium.In one case,a nonthickened endometrium was observed,while in another,hyperplasia of the endometrium was seen.Notably,none of these patients had malignant tumors identified in the uterine cavity via MRI scans.However,postoperative pathological results following hysterectomy consistently indicated cervical stromal invasion.CONCLUSION Cervical stromal invasion is easily missed if no cancer is found in the uterine body on MRI.Immunohistochemistry of endoscopic curettage specimens should be conducted to avoid underestimation of the disease.

Value of Intrauterine Autologous Platelet-Rich Plasma Therapy on Endometrial Receptivity:A Literature Review

Endometrial receptivity is an important factor that influences embryo implantation.Thus,it is important to identify an applicable approach to improve endometrial receptivity in women undergoing assisted reproductive technology.Recently,growing evidence has indicated that intrauterine platelet-rich plasma(PRP)infusion is an effective method to obtain a satisfactory reproductive outcome by increasing endometrial thickness and improving endometrial receptivity.Therefore,the present review aims to outline the possible mechanisms of PRP on endometrial receptivity and summarize the present literature on the effects of PRP therapy in improving endometrial receptivity.

Effectiveness of treating menorrhagia using microwave endometrial ablation at a frequency of 2.45 GHz

BACKGROUND Microwave endometrial ablation(MEA)is a minimally invasive treatment for menorrhagia.It has been covered by the national insurance in Japan since April 2012,and its demand has been increasing as the importance of women’s health has advanced in society.AIM To examine the efficacy of MEA as a treatment option for menorrhagia.METHODS In this study,we retrospectively analyzed 76 patients who underwent MEA between January 2016 and March 2020 in our department.MEA was performed in the lithotomy position,under general anesthesia,and with transabdominal ultrasound guidance,including the entire endometrial circumference while confirming endometrial coagulation.The Microtaze AFM-712 and the Sounding Applicator CSA-40CBL-1006200C were used for MEA,and the endometrium was ablated using a Microtaze output of 70 W and coagulation energization time of 50 s per cycle.The visual analog scale(VAS)was used to evaluate menorrhagia,menstrual pain,and treatment satisfaction.Additionally,the hemoglobin(Hb)levels before and after MEA and associated complications were investigated.RESULTS The average age of the patients was 44.8±4.0 years.While 14 patients had functional menorrhagia,62 had organic menorrhagia,of whom 14 had endometrial polyps,40 had uterine fibroids,and 8 had adenomyosis.The VAS score before MEA and 3 and 6 mo after the procedure were 10,1.3±1.3,and 1.3±1.3,respectively,for menorrhagia and 10,1.3±1.8,and 1.3±1.8,respectively,for menstrual pain,both showing improvements(P<0.001).The MEA Hb level significantly improved from 9.2±4.2 g/dL before MEA to 13.4±1.2 g/dL after MEA(P=0.003).Treatment satisfaction was high,with a VAS score of 9.6±0.7.Endometritis was observed in one patient after surgery and was treated with antibiotics.CONCLUSION MEA is a safe and effective treatment for menorrhagia.

Apigenin, a natural flavonoid, promotes autophagy and ferroptosis in human endometrial carcinoma Ishikawa cells in vitro and in vivo

Apigenin,a natural flavonoid has been reported against a variety of cancer types.However,it is unclear whether apigenin can promote autophagy and ferroptosis in Ishikawa cells.There are few reports on the mechanism of apigenin on autophagy and ferroptosis of endometrial cancer Ishikawa cells.We found that iron accumulation,lipid peroxidation,glutathione consumption,p62,HMOX1,and ferritin were increased,while,solute carrier family 7 member 11 and glutathione peroxidase 4 were decreased.Ferrostatin-1,an iron-death inhibitor could reverse the effects of apigenin in Ishikawa cells.On the other hand,apigenin could promote autophagy via up-regulating Beclin 1,ULK1,ATG5,ATG13,and LC3B and down-regulating AMPK,mTOR,P70S6K,and ATG4.Furthermore,apigenin could inhibit tumor tissue proliferation and restrict tumor growth via ferroptosis in vivo.

Synchronous endometrial and ovarian cancer: A case report

BACKGROUND Synchronous endometrial and ovarian cancer(SEOC)is a rare genital tract tumor.Precise diagnosis is crucial for the disease management since prognosis and overall survival differ substantially between metastatic endometrial cancer(EC)or OC.In this review we present 2 cases of women who were diagnosed with SEOC,and discuss the clinical characteristic of SEOC,diagnostic and molecular profiling issues.Next generation sequencing of 10 gene panel was performed on cancerous tissue and uterine lavage samples.CASE SUMMARY In our report patients with SEOC had endometroid type histology with early stage and low-grade histology for both EC and OC.They underwent surgical treatment and staging.Next-generation sequencing of 10 gene-panel identified CTNNB1,PIK3CA,and PTEN gene mutations in ovarian tissue in one case,while none of these genes were mutated in other case.Literature review in support to our data suggest a good prognosis for SEOC diagnosed at early stage.CONCLUSION Accurate diagnosis of SEOC is essential for disease management and gene mutation analysis can be helpful as a complementary diagnostic and prognostic tool.

LiNA OperaScope^(TM) for microwave endometrial ablation for endometrial polyps with heavy menstrual bleeding: A case report

BACKGROUND The procedure for microwave endometrial ablation(MEA)follows established MEA practice guidelines but requires hysteroscopic observation of the uterine lumen before and after MEA.When a luminal uterine lesion is recognized,its removal requires preoperative dilation of the cervix because the outer diameter of a conventional rigid hysteroscope is 8.7 mm.Recently,a fully disposable rigid hysteroscope(LiNA OperaScope^(TM))with a narrow diameter(4.4 mm)and forceps capable of extracting endometrial lesions has become available.CASE SUMMARY Here,we report a case of heavy menstrual bleeding(HMB)complicated by endometrial polyps where MEA was performed after removing endometrial polyps using the LiNA OperaScope^(TM) device.A 48-year-old woman with three prior pregnancies and three deliveries was referred to our hospital for further examination and treatment after being diagnosed with HMB 2 years earlier.The patient underwent MEA following endometrial polypectomy using LiNA OperaScope^(TM).After MEA,endometrial cauterization was again examined using the LiNA OperaScope^(TM),and the procedure was completed.No preoperative cervical dilation was performed.The patient’s clinical course was favorable,and she was discharged 3 h after surgery.One month after surgery,menstruation resumed,and both HMB and dysmenorrhea improved markedly from 10 preoperatively to 1 postoperatively,as assessed subjectively using the visual analog scale.The patient’s postoperative course was uneventful with no complic-ations.CONCLUSION LiNA OperaScope^(TM) can be a minimally invasive treatment for MEA of HMB with uterine lumen lesions.

Superiority of indocyanine green-enhanced near-infrared fluorescence-guided imaging for laparoscopic lymph node dissection in patients with early-stage endometrial cancer: A retrospective cohort study

Objective:Laparoscopic pelvic lymph node dissection(LPND),which is an effective therapy for endometrial cancer,is challenging because of the complexity of the procedure and the occurrence of postoperative complications.This study aimed to explore whether indocyanine green(ICG)-enhanced nearinfrared(NIR)fluorescence-guided LPND is superior to LPND in the context of early-stage endometrial carcinoma.Methods:In this retrospective study,we included the medical records of 190 patients with early-stage endometrioid adenocarcinoma who underwent LPND at the Department of Obstetrics and Gynecology,Sir Run Run Shaw Hospital,Zhejiang University School of Medicine between January 2019 and January 2021.Depending on whether ICG-enhanced NIR fluorescence guidance was used,the patients were assigned to the ICG group or non-ICG group.Patients were followed-up for one year after surgery.Data on demographic characteristics,pathological results,operative outcomes,and complications were collected and analyzed.Results:The baseline characteristics were comparable between the ICG group and non-ICG group,including age,BMI,pregnancy history,and preoperative hemoglobin.For surgical outcomes,the patients in ICG group had significantly lower intraoperative blood loss(50 mL vs.120 mL,p<0.001),less postoperative pelvic drainage time(4.14±1.44 d vs.5.70±1.89 d,p¼0.001),shorter duration of hospital stay(5.26±1.41 d vs.7.37±1.85 d,p¼0.003),higher number of positive pelvic lymph nodes(PLNs)(1 vs.0,p¼0.003),and more PLN-positive cases(16.0%vs.3.6%,p¼0.003)than the patients in non-ICG group.However,no significant differences were noted in blood transfusion requirement,operative time,hemoglobin level decreases,number of PLNs harvested,or the presence of lymphocysts between the two groups.Conclusion:Our study showed that ICG-enhanced NIR fluorescence-guided operation may improve the accuracy and safety of LPND.

Endometriosis-associated endometrioid adenocarcinoma of the fallopian tube synchronized with endometrial adenocarcinoma:A case report

BACKGROUND Endometriosis is a common gynecological disorder that affects women of reproductive age.It is characterized by a cancer-like invasion of the extra-uterine endometrium and exhibits a strong association with ovarian clear cell cancer and endometrioid cancer.Endometriosis-associated fallopian tube endometrioid adenocarcinoma synchronized with endometrial adenocarcinoma was rarely reported.CASE SUMMARY A 49-year-old woman was referred to our hospital complaining about abnormal vaginal bleeding for three years following unsatisfactory medication.Intraop-erative frozen sections unexpectedly unveiled an endometrioid cancer of the left fallopian tube with superficial invasion surrounded by diffuse endometriosis synchronized with endometrioid endometrial cancer.CONCLUSION It was difficult to make a differential diagnosis when confronted with incidental findings of fallopian tube cancer lesions synchronized with endometrial cancer.The key differential diagnosis of primary endometriosis-associated endometrioid adenocarcinoma of the fallopian tube from endometrial adenocarcinoma invol-vement relies on the pathological identification of malignant transformation in fallopian tube endometriosis disease.

The correlation of miRNA expression and tumor mutational burden in uterine corpus endometrial carcinoma

Background:The relationship between microRNA(miRNA)expression patterns and tumor mutation burden(TMB)in uterine corpus endometrial carcinoma(UCEC)was investigated in this study.Methods:The UCEC dataset from The Cancer Genome Atlas(TCGA)database was used to identify the miRNAs that differ in expression between high TMB and low TMB sample sets.The total sample sets were divided into a training set and a test set.TMB levels were predicted using miRNA-based signature classifiers developed by Lasso Cox regression.Test sets were used to validate the classifier.This study investigated the relationship between a miRNA-based signature classifier and three immune checkpoint molecules(programmed cell death protein 1[PD-1],programmed cell death ligand 1[PD-L1],cytotoxic T lymphocyte-associated antigen 4[CTLA-4]).For the miRNA-based signature classifier,functional enrichment analysis was performed on the miRNAs.An analysis of the relationship between PD-1,PD-L1,and CTLA-4 immune checkpoint genes was carried out using the miRNA-based signature classifier.Results:We identified 27 differentially expressed miRNAs in miRNA-base signature.For predicting the TMB level,27-miRNA-based signature classifiers had accuracies of 0.8689 in the training cohort,0.8276 in the test cohort,and 0.8524 in the total cohort.The correlation between the miRNA-based signature classifier and PD-1 was negative,while the correlation between PD-L1 and CTLA4 was positive.Based on the miRNA profiling described above,we validated the expression levels of 9 miRNAs in clinical samples by quantitative reverse transcription PCR(qRT-PCR).Four of them were highly expressed and many cancer-related and immune-associated biological processes were linked to these 27 miRNAs.Thus,the developed miRNA-based signature classifier was correlated with TMB levels that could also predict TMB levels in UCEC samples.Conclusion:In this study,we investigated the relationship between a miRNAbased signature classifier and TMB levels in Uterine Corpus Endometrial Carcinoma.Further,this is the first study to confirm their relationship in clinical samples,which may provide more evidence support for immunotherapy of endometrial cancer.

Identification of STAT5B as a biomarker for an early diagnosis ofendometrial carcinoma

Background: The late detection of endometrial carcinoma (EC) at an advanced stage often results in a poorpatient prognosis. It is hence important to identify reliable biomarkers to facilitate early detection of EC. Signaltransducer and activator of transcription (STAT) family members play an important role in several tumors, however,their impact on EC development and progression remains unclear. Methods: Machine learning methods were used toinvestigate the importance of STAT5B in EC. Results: Hence, we explored the UALCAN data mining platform andfound that while STAT1 and STAT2 were upregulated, STAT5A, STAT5B, and STAT6 were downregulated in EC.This high expression of STAT5B and STAT6 predicted favorable clinical outcomes, whereas the increased expressionof STAT1 and STAT2 predicted poor clinical outcomes. Subsequent pathway enrichment analysis revealed that theSTAT family was mainly involved in apoptosis pathway activation, cell cycle disruption, and epithelial–mesenchymaltransition. Drug sensitivity analysis demonstrated that STAT5A/5B expression was negatively correlated with drugresistance in EC. Further, the expression of STAT5B mRNA and protein was correlated with severalclinicopathological characteristics. Tumor Immune Estimation Resource (TIMER) analysis revealed that STAT5Bexpression was positively correlated with the abundance of infiltrating CD8+ T cells and neutrophils while its copynumber variation was associated with the overall immune cell infiltration. The data on the correlations betweenSTAT5B expression and related genes in uterine corpus endometrial carcinoma (UCEC) in cBio Cancer Portalshowed the closest correlation of STAT5B expression with that of KIAA0753 (also known as moonraker and OFIP),followed by COL27A1 in EC. Pathway enrichment analysis further showed that STAT5B-related genes were involvedin the mitogen-activated protein kinase (MAPK) and Ras signaling pathways. Conclusion: Collectively, our findingsprovided new insights into the role of the STAT family in EC. It also highlighted new targets for future research ondiagnostic and prognostic markers and STAT5B as a novel marker for drug sensitivity screening.

Efficacy and prognosis of adjuvant treatment of endometrial cancer with medroxyprogesterone acetate COX regression analysis

BACKGROUND Endometrial cancer is one of the most commonly diagnosed gynecological cancers worldwide,and early-stage high-risk endometrial cancer has a poor prognosis.Adjuvant treatments after surgery,such as chemotherapy and radiotherapy,have been widely used in clinical practice to improve patient survival.Medroxyprogesterone acetate is a synthetic progestogen that has been reported to have potential anticancer effects in endometrial cancer.However,its efficacy,safety,and longterm prognostic benefits as an adjuvant treatment for endometrial cancer remain controversial.Therefore,this study aimed to observe the efficacy and prognostic impact of adjuvant medroxyprogesterone acetate treatment in patients with earlystage high-risk endometrial cancer and evaluate its safety.AIM To observe the efficacy and prognosis of adjuvant treatment of endometrial cancer with medroxyprogesterone acetate and to evaluate its safety.METHODS We collected the clinical data of 200 patients with early-stage high-risk endometrial cancer who were admitted to the Department of Obstetrics and Gynecology of our hospital from January 2018 to December 2022.The control group(100 patients)underwent conventional surgical treatment,and the study group(100 patients)was administered adjuvant medroxyprogesterone acetate tablets on top of the control group.The Kaplan-Meier curve analysis and log-rank test were performed to determine the possible factors influencing the 5-year cumulative survival rate in the patients.The Cox regression analysis was performed to identify the factors influencing the survival prognosis of endometrial cancer.RESULTS According to the Cox regression analysis,age[hazard ratio(HR)=4.636,95%confidence interval(95%CI):1.411-15.237],pathological type(HR=6.943,95%CI:2.299-20.977),molecular typing(HR=5.789,95%CI:3.305-10.141),and myometrial infiltration(HR=5.768,95%CI:1.898-17.520)were factors influencing the prognosis of patients with early-stage high-risk endometrial cancer.CONCLUSION Age,pathological type,molecular typing,and myometrial infiltration were all relevant factors affecting the prognosis of early-stage high-risk endometrial cancer.The potential long-term prognostic benefit of adjuvant postoperative radiotherapy in patients with early-stage high-risk endometrial cancer is worthy of clinical consideration.

Expression and function of long non-coding RNA DLX6-AS1 in endometrial cancer

Background:LncRNA DLX6-AS1 has been uncovered to exert effects on various cancers.Nevertheless,the impacts of DLX6-AS1 on endometrial cancer(EC)development remained obscure.The study explored the influence of DLX6-AS1 on EC progression via the microRNA(miR)-374a-3p/zinc-finger protein(ZFX)axis.Methods:EC cell lines were collected and DLX6-AS1,miR-374a-3p,and ZFX levels in EC cell lines were detected.The EC cells were transfected with DLX6-AS1,miR-374a-3p,and ZFX constructs to examine the biological functions of EC cells.The xenograft model was established for detecting tumor growth.Rescue experiments were conducted to verify the interaction of DLX6-AS1,miR-374a-3p,and ZFX in EC cells.Results:DLX6-AS1 and ZFX levels were elevated,while miR-374a-3p exhibited a reduced level in EC cells.Silencing DLX6-AS1 and elevated miR-374a-3p expressions repressed the biological activities of EC cells.Reduced DLX6-AS1 repressed tumor development.MiR-374a-3p silencing reversed the impacts of DLX6-AS1 silencing,while ZFX overexpression abrogated the impacts of miR-374a-3p elevation on EC cell growth.Mechanically,DLX6-AS1 was found to bind to miR-374a-3p,and miR-374a-3p targeted ZFX.Conclusion:DLX6-AS1 depletion restricts the malignant phenotype of EC cells.The study might provide novel therapeutic biomarkers for EC treatment.

Endometrial Status and Embryonic Implantation about 150 Cases at the Medically Assisted Procreation Laboratory “Le Diafounou”

Background: The endometrium is the tissue that lines the inside of the uterus. It undergoes multiple changes during the menstrual cycle and prepares to welcome the fertilized egg. Endovaginal ultrasound is a first-line examination in the assessment of female infertility. Objective: We aimed to determine the impact of endometrial status by endovaginal ultrasound on the outcome of embryo transfers. Subjects and Methods: This was a prospective cross-sectional study of 150 women collected between January and October 2020 at the “Le Diafounou” medically assisted procreation laboratory. Were included in the study, women presenting for desire of pregnancy and having continued the treatment until the transfer of fresh or frozen embryos. An uterine score was used. This score took into account the thickness of endometrium, it is coffee bean aspect, the presence of the notch, the echogenicity of the endometrium, the pulsatility index, the presence of the flow at the end of diastole and sub-endometrial flow. Ultrasounds were performed using a General Electric logic 500, logic 9 and Voluson E8 device. The data was entered into Excel and then analyzed using SPSS version 21. Results: 150 women were selected for the study. 83 women or 55.3% were between 17 and 35 years old and 44.7% were over 35 years old with an upper limit of 50 years old. The number of women who became pregnant was 69% or 46%. The average thickness of the endometrium was 11.40 mm with extremes of 4.65 mm and 18.6 mm. There was a correlation between the thickness of the endometrium and obtaining a pregnancy (p i.e. 88.7%. The pulsatility index was relatively low for those who started a pregnancy, i.e. 90%. The high pulsatility index is one of the reasons for the failure of embryo implantation. The correlation was significant (p = 0.009). 141 women had no notch in the uterine arteries, i.e. 94%. 94 women or 62.7% had a triple line endometrium or typical coffee bean appearance. End-diastolic flow was observed in 127 women, i.e. 84.7%. The sub-endometrial flow was found in 128 women or 85.3%. Conclusion: The Knowledge of the status of the endometrium is essential and has an impact on the outcome of embryo transfers. The thinner (7 and <15). Doppler factors also play an important role.