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.

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.

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.

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.

An elevated preoperative serum calcium level is a significant predictor for positive peritoneal cytology in endometrial carcinoma

Objective:To evaluate preoperative serum calcium concentration and investigate the association between calcium level and positive peritoneal cytology in endometrial carcinoma(EC).Methods:A total of 510 patients who were diagnosed with EC and had surgery were initially enrolled in this study at Peking University People's Hospital between January 2012 and December 2016.Clinical characteristics and preoperative serum calcium,albumin,carbohydrate antigen(CA)125,CA19-9,carcinoembryonic antigen(CEA)were extracted from patient records and evaluated according to postoperative peritoneal cytology.Predictive factors were assessed with Cox univariate and multivariate analyses.Factors selected from multivariate analysis results were used to build a predictive model.Results:A total of 510 patients are identified in our database and 444 patients who fulfilled inclusion and exclusion criteria are included in this study.Univariate analysis revealed that ionized calcium concentration was closely related to positive peritoneal cytology,tumor grade and lymph-vascular space invasion(LVSI).Moreover,peritoneal cytology was significantly associated with hypertension,tubal ligation,serum CA125,CA19-9,CEA and ionized calcium level.Multivariate analysis revealed that albumin-adjusted calcium level,CA125 and tubal ligation were independent predictive factors of positive peritoneal cytology(P<0.05).A combination of ionized calcium level with the other two indexes yielded significantly great area under the curve(AUC=0.824).Conclusions:This study enhanced the value of preoperative ionized calcium level.We also identified several potential biomarkers to predict positive peritoneal cytology in EC patients before surgery.

Expressions of estrogen receptor subtypes and c-met proto-oncogene in endometrial carcinoma and their correlation

Objective To investigate the expressions of estrogen receptor(ER)subtypes and c-met proto-oncogene in human endometrial carcinomas and to assess the clinical significance of ER and c-met in this carcinoma.Methods Reverse transcription PCR(RT-PCR)was used to detect the expressions of ERα,ERβ and c-met proto-oncogene mRNA in 30 samples of endometrial carcinoma and 11 samples of normal endometrium.Results The expression of ERα in endometrial carcinoma(0.70±0.40)was significantly reduced in comparison to that in normal endometrium(1.14±0.56,P<0.05).A similar finding was made for the expression of ERβ in carcinoma(0.24±0.18)versus normal tissues(0.48±0.20,P<0.05).In contrast,c-met mRNA expression was increased in endometrial carcinoma(1.45±0.72)compared to that in normal endometrium(0.42±0.31,P<0.01).A decrease tendency of the expression of ERα was also found from Stage Ⅰ(0.82±0.41)to a more severe Stag Ⅱ-Ⅲ of endometrial carcinoma(0.42±0.17,P<0.05).The analysis of ERα and ERβ mRNA revealed a decrease tendency from shallow to deep invasion of the uterine muscles(P<0.05).We found that the expressions of ERα and ERβ were negatively correlated with c-met proto-oncogene with a coefficient correlation of-0.63(P<0.01)and-0.32(P<0.05),respectively.Conclusion ERα and ERβ are both involved in mutagenic action of carcinogen.C-met proto-oncogene plays an important role in the carcinogenesis and development of endometrial carcinoma.C-met and ER expressions show a negative correlation in the development of endometrial carcinoma.

Clinial Implication of tThe Expression of Aurora B in Normal Endometrium and Endometrial Carcinoma

The expression of Aurora B in normal endometria and endometrial carcinomas and its relation with clinicopathologic parameters of endometrial carcinomas were investigated. Streptavidin-biotin peroxidase （SP） immunohistochemical technique was used to detect the expression of Aurora B in 10 cases of normal proliferative phase endometria, 10 cases of normal secretory phase endometria and 72 cases of endometrial carcinomas respectively. According to the 1988 International Federation of Gynecology and Obstetrics （FIGO） grade, there were 37 patients in grade 1, 23 in grade 2 and 12 in grade 3 respectively. According to the FIGO stage, there were 59 patients in stage Ⅰ-Ⅱ and 13 patients in stage Ⅲ-Ⅳ. Aurora B was expressed in both normal proliferative phase endometria, secretory phase endometria and endometrial carcinomas, but its positive labeling index （PLI） in proliferative phase endometria was significantly higher than that in secretory phase endometria （P〈0.01） and endometrial carcinomas （P〈0.01）. The PLI of Aurora B was lower in tumors with well differentiation （G1）, low surgical staging （Ⅰ-Ⅱ）, and ≤1/2 myometrial invasion than that in tumors with moderate and low differentiation （G2--G3）, higher surgical staging （Ⅲ-Ⅳ）, and 〉1/2 myometrial invasion （all P〈0.01）. Aurora B exerts its functions in the replication of normal endometrial glandular cells; Expression of Aurora B is significantly correlated with biologic behavior of endometrial carcinoma, indicating that Aurora B may be a promising prognostic factor in endometrial carcinoma.

Adjuvant Chemotherapy versus Radiotherapy in High-risk,Early-stage Endometrioid Endometrial Carcinoma

Objective:The present study was designed to evaluate the effects of adjuvant chemotherapy(CT)vs.radiotherapy(RT,alone or combined with CT)on the prognosis of patients with high-risk,early-stage(stage I and stage II)endometrioid endometrial carcinoma.Methods:This single-center retrospective clinical study was conducted in Union Hospital,Tongji Medical College,Huazhong University of Science and Technology between 2010 and 2019.

Effect of Celecoxib on Apoptosis of Endometrial Carcinoma Cell

Objective： To investigate the effect of Celecoxib on proliferation and apoptosis of the endometrial carcinoma cell HEC-1B and the effect on the expression of Fas and Survivin mRNA. Methods： The inhibition on the growth of human endometrial carcinoma cell HEC-1B was investigated by cell culture and MTT experiment when treated with different concentrations of Celecoxib. The cell apoptosis was detected by flow cytometry and DNA Ladder Electrophoresis. The change of the expression of Fas and Survivin mRNA after the treatment of Celecoxib was detected With RT-PCR. Results： Celecoxib could effectively inhibit the growth of HEC-1B cells and induce apoptosis. Survivin mRNA expression was decreased and Fas mRNA expression was increased after treating with Celecoxib. Conclusion： Celecoxib could inhibit HEC-1B cell proliferation and induce its apoptosis.

EXPRESSION AND SIGNIFICANCE OF SMAD4 AND p21WAF1 IN ENDOMETRIAL CARCINOMA

Objective: To investigate the expression of Smad4 and p21WAF1 in endometrial carcinoma and its clinical significance. Methods: Immunohistochemical method wasused to detect Smad4 and p21WAF1 expression in 56 cases of endometrial carcinoma. Results: The positive rate ofSmad4 was 80.36% in endometrial carcinoma. The Samd4 expression was significantly correlated with histologicalgrade (P<0.01) and clinical stage (P<0.05). The positive rate of p21WAF1 was 64.28% in endometrial carcinoma. Theexpression of p21WAF1 was correlated with depth ofmyometrial invasion (P<0.01). There was no correlation between Smad4 and p21WAF1 expression (P>0.05). Conclusion: Smad4 may play an important role in the tumorigenesis, differentiation and progression ofendometrial carcinoma. The expression of p21WAF1 wasassociated with the tumorigenesis of endometrial carcinoma, but the association between p21WAF1 and differentiationand progression of endometrial carcinomas needs to befurther investigated.

EXPRESSION AND SIGNIFICANCE OF PTEN IN ENDOMETRIAL CARCINOMA

Objective: To investigate the expression of PTEN in endometrial carcinoma and its clinical significance. Methods: Reverse transcriptase-polymerase chain reaction and Western-blot methods were used to detect PTEN expression in 28 cases of endometrial carcinoma. Results: mRNA and protein expression levels of PTEN in endometrial carcinomas were significantly lower than those in normal endometrium (P<0.01). Conclusion: PTEN may play an important role in the tumorigenesis of endometrial carcinoma.

Immunocytochemical examination of PTEN and Ki-67 for endometrial carcinoma using thin-layer endometrial preparations

The current study is designed to evaluate certain immunocytochemical(ICC)biomarkers to gain a better cytodiagnosis.For this purpose,85 patients from March 2016 to March 2019 who planned to get a hysteroscopy assay were recruited.Cytological sampling was conducted by scratching the uterus cavity using SAP-1,and the samples were processed as liquid-based smears,using SurePath technology.36 patients diagnosed with EC or atypical endometrial hyperplasia were recruited in this study.33 cases were diagnosed with EC,and 3 cases were diagnosed with atypical endometrial hyperplasia,allocated with EC or precancerous lesions group.26 cases were diagnosed with benign lesions group.Among these cases,9 cases were diagnosed with endometrial simple hyperplasia,2 cases were diagnosed with complicated hyperplasia,5 cases were diagnosed with an irregular proliferation of endometrium and 10 cases were diagnosed with endometrial polyps.There were 23 cases in the healthy group.Staining in thin-layer endometrial preparations by ICC and using H-score or counting the percentage of stained cells.The presentation of PTEN in normal endometrium,benign lesions,and EC/precancerous lesions were different(p<0.01).Taking the cut-off value of 50(Youden’s index:0.698)PTEN expression for the diagnosis of EC/precancerous lesion,the sensitivity and specificity were 83.7%and 86.1%.The presentation of Ki-67 in normal endometrium,benign lesions,and EC/precancerous lesions were different(p<0.01).Taking the cut-off value of 15%(Youden’s index:0.76)Ki-67 expression for the diagnosis of EC/precancerous lesion,the sensitivity and specificity were 94.4%and 81.6%.In this study,the use of different cut-off values for Ki-67 and PTEN helped differentiate endometrial lesions.Immunocytochemistry in the ECT detection of PTEN and Ki-67 can improve the diagnostic capabilities of endometrial cancer and precancerous lesions.

Magnetic Resonance Evaluation of Transplanted Endometrial Carcinoma and Its Lymph Node Metastasis in Rabbits

Objective： To establish a rabbit model of transplanted endometrial carcinoma with lymph node metastasis and observe its magnetic resonance imaging （MRI） features. Methods： VX2 tumor grafts were orthotopically embedded in the endometrium of rabbits, and 3 weeks after the transplantation, thetumor and its metastasis to the retroperitoneal lymph nodes were examined by MRI, and the signal intensities and size of the lymph nodes were compared with those of normal rabbits. Results： The orthotopic transplantation of the tumor grafts resulted in tumor growth in all the 12 recipient rabbits. The tumors infiltrated the serosa of the uterus and metastasized to the retroperitoneal lymph nodes 3 w after transplantation. MRI demonstrated that the lymph nodes of the tumor-bearing rabbits were larger in size than those of normal control rabbits, but the signal intensity of the lymph nodes was not significantly different between them. Conclusion： This transplanted endometrial carcinoma model is characterized by high success rate and similar tumor metastasis behaviors with human endometrial carcinoma, therefore may serve as a good model for testing the efficacy of contrast agents for MR lymphography.

Seeking for endometrial carcinoma-related genes and their bioinformatics analysis

Objective:Screening and excavating genes and biological information related to endometrial carcinoma(EC),to provide novel means for clinical diagnosis and treatment.Methods:The gene chip data of EC was obtained from the Gene Expression Omnibus(GEO)database,we integrated gene discrepantly expressive gene analysis,enrichment of genic function and pathway analysis,protein-protein interaction(PPI)network and literature mining to predict genes and pathways of EC.Results:Functional enrichment analysis identified 976differential expression genes were participated in cell cycle regulation,proliferation,biosynthesis,protein phosphorylation and fission biological process,etc.We found eight significantly up-regulated pathways in the microarray datasets,including the MAPK signaling pathway and mTOR pathway,and six down-regulated pathways,including the P53signaling pathway and cell cycle.Gene protein related interaction network analysis was further performed,and we found twelve distinct genes,including the PCNA and CCND1,these genes were located in key position of EC related network,which may be related to the pathogenesis and progression of EC.Furthermore,there was a high correlation between PCNA and CCND1with EC by consulting the related literature and data,however,the functional mechanism was uncleared.Conclusion:The pathogenesis and progression of EC may involve in several different pathways and genes,the genes PCNA,CCND1and MAPK signaling pathway may be valuable.

THE EXPRESSION OF p16 AND CYCLIN D_1 IN PROLIFERATIVE ENDOMETRIUM AND ENDOMETRIAL CARCINOMA

Objective To study the role of p16 and cyclin D 1 in the genesis and development of endometrial carcinoma.Methods 12 cases of normal endometrium,22 cases of proliferative endometrium and 41 cases of endometrial carcinoma were detected for the expression of p16 and cyclin D 1 by means of immunohistochemical S P. Results In normal endometrium p16 was expressed while cyclin D 1 was almost negative in the proliferative phase,but both of them were negative in the secretory phase.Among the groups of the simple and compound hyperplasia, the atypical hyperplasia and the endometrial carcinoma,the expression of p16 showed a descending tendency, while the expression of cyclin D 1 showed an ascending tendency.In endometrial carcinomas the expression of p16 was significantly lower than that of normal endometrium and proliferative endometrium( P <0.01, P <0.05).However, the expression of cyclin D 1 in proliferate endometrium and endometrial carcinoma was significantly higher than that in normal endometrium ( P<0.05,P<0.01) .The overexpression of cyclin D 1 in the atypical hyperplasia group was obviously different from that in the simple and compound hyperplasia group ( P <0.01).In endometrial carcinoma,the expression of p16 was decreasing with the descending of cell differentiate degree, on the opposite, the expression of cyclin D 1 was increased and there existed a negative correlation between them.It was also observed that the overexpression of cyclin D 1 was significant different between G 1 and G 2,G 3(P<0.01).Conclusion p16 is a negative regulating factor of cell cycle in endometrial carcinoma, while cyclin D 1 is a positive one.Both of them are important in the genesis and development of endometrial carcinoma.The low expression of p16 and the overexpression of cyclin D 1 are related with the malicious biological behaviors of endometrial carcinoma and maybe play an important role in the judgement of prognosis.Overexpression of cyclin D 1 may be an earlier molecular event in the genesis of endometrial carcinoma.

Clinical significance of survivin in the diagnosis and prognosis of endometrial carcinoma

Objective： To investigate the clinical significance of survivin in endometrial carcinoma and to investigate the relationship between the expression of survivin and Ki-67. Methods： Immunohistochemical S-P （streptavidin-biotin-peroxidase complex）method was performed to detect the expression of survivin and Ki-67 antigen in 15 cases of normal endometrium, 21 cases of endometrial simple and complex hyperplasia, 22 cases of endometrial atypical hyperplasia, and 61 cases of endometrial carcinoma. Results： Survivin was hardly detected in some normal endometrium in the proliferative phase and in the secretory phase. However, the level of survivin expression in atypical hyperplasia endometrium（72.73%）was higher than that in normal en- dometrium （7.14%）（P 〈 0.05）, including simple and complex hyperplasia （42.38%）（P 〈 0.01 ）, and was lower than that in endometrial carcinoma（90.17%）（P 〈 0.05）. Moreover, significant correlation was present between the expression of survivin and the characteristics of endometrial carcinoma, including clinical stage, histological grade and the presence of invasion to myometrium （P 〈 0.05）. In addition, Ki-67 antigen expression was positively correlated with survivin expression in all specimen. Ki-67 labeled indexes （LIs）in hyperplasia endometrium were significantly lower than those in atypical hyperplasia endometrium and endometrial carcinoma （P 〈 0.01 ）, while there was no significant difference in Ki-67 LIs between atypical hyperplasia endometrium and endometrial carcinoma（P 〉 0.05）. There was no significant relationship between Ki-67 LIs and the characteristics of endometrial carcinoma, including histological grade, clinical stage or the invasion to myometrium（P 〉 0.05）. Conclusion： Survivin may participate in the onset and progression of endometrial carcinoma through inhibiting apoptosis and promoting proliferation. Survivin expression is correlated with the malignant degree and prognosis of tumor. Ki-67 is also associated with carcinogenesis and progression of endometrial carcinoma. The results suggest that survivin could be a diagnostic and prognostic marker for endometrial carcinoma and might provide pathways to treat the patients with recurrent or refractory or rudimental endometrial carcinoma.

Construction and validation of a prognostic risk model for uterine corpus endometrial carcinoma based on alternative splicing events

Objective To establish a prognostic risk model for uterine corpus endometrial carcinoma(UCEC)based on alternative splicing(AS)event data from The Cancer Genome Atlas(TCGA)and assess the accuracy of the model.Methods TCGA and SpliceSeq databases were used to acquire a summary of AS events and clinical data related to UCEC.Bioinformatic analysis was performed to identify differentially expressed AS events in UCEC.Least absolute shrinkage and selection operator(LASSO)regression and multivariate Cox regression analyses were used for constructing a prognostic risk model.Next,using the receiver operating characteristic(ROC)curve,Kaplan-Meier survival analysis,and independent prognostic analysis,we assessed the accuracy of the model.In addition,a splicing network was established based on the association between potential splicing factors and AS events.Results We downloaded clinical data and AS events of 527 UCEC cases from TCGA and SpliceSeq databases,respectively.We obtained 18,779 survival-associated AS events in UCEC using univariate Cox regression analysis and 487 AS events using LASSO regression analysis.Multivariate Cox regression analysis established a prognostic risk model for UCEC based on the percentage splicing value of 13 AS events.Independent prognostic effect on UCEC risk was then assessed using multivariate and univariate Cox regression analyses(P<0.001).The area under the curve was 0.827.The pathological stage and risk score were independent prognostic factors for UCEC.Herein,we established a regulatory network between alternative endometrial cancer-related splicing events and splicing factors.Conclusion We constructed a prognostic model of UCEC based on 13 AS events by analyzing datasets from TCGA and SpliceSeq databases with medium accuracy.The pathological stage and risk score were independent prognostic factors in the prognostic risk model.

Clinical Study of Magnetic Resonance Imaging,Diffusion Weighted Imaging and Dynamic Contrast-enhanced Imaging in the Diagnosis of Endometrial Carcinoma

Objective:To evaluate the value of DWI,DCE-MRI and magnetic resonance imaging(MRI)in the diagnosis of endometrial cancer.Method:The MRI,DWI and DCE-MRI imaging data of 80 patients with suspected endometrial cancer were analyzed.The diagnostic value of MRI,DWI and DCE-MRI in endometrial cancer was analyzed based on the postoperative pathological diagnosis results.The diagnostic efficacy of quantitative parameters Ktrans value,Kep value,Ve value and ADC in endometrial cancer was analyzed by ROC.Result:Among the 80 patients,61 had endometrial carcinoma and 19 had benign endometrial disease.The accuracy of MRI,DWI and DCE-MRI in the diagnosis of endometrial cancer was 57.38%,63.93%and 80.33%,respectively.The specificity was 78.95%,82.41%and 84.21%,respectively.The ADC values of endometrial cancer patients were lower than those of benign patients(P<0.05),and the values of Ktrans,Kep and Ve were higher than those of benign patients(P<0.05).The ktrans and ADC in the diagnosis of endometrial cancer were higher,which was 0.922(95%CI:0.864-0.992,P=0.000)and 0.872(95%CI:0.767-0.977.P=0.000),respectively.Conclusion:DWI and DCE-MRI had high value in the diagnosis of endometrial cancer.Its parameters,Ktrans and ADC,can be used as quantitative indicators for the early diagnosis of endometrial cancer.

Diagnostic value and clinical significance of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio combined with carbohydrate antigen in endometrial carcinoma

Background:To explore diagnostic value and clinical significance of preoperative neutrophil-to-lymphocyte ratio(NLR)and platelet-to-lymphocyte ratio(PLR)combined with serum carbohydrate antigen(CA),including CA125,CA153 and CA199,in endometrial cancer(EC).Methods:The clinical data of 135 patients who underwent endometrial pathology examination in our hospital from January 2014 to June 2019 were retrospectively analyzed,including 65 cases of EC,40 cases of proliferative endometrial lesions and 50 cases of normal endometrium.Blood routine analyzer and electrochemical luminescence method were used to detect 5 parameters of NLR,PLR,CA125,CA153 and CA199 in these patients.The study explored the relationship between the five indicators and different levels of endometrial lesions,and analyzed their relationship with clinical pathological characteristics of EC patients.The diagnostic efficacy of NLR,PLR,CA,NLR combined CA,PLR combined CA was evaluated by receiver operating curve(ROC)combined with logistic regression equation.Results:The expression of the five parameters was different in different levels of endometrial lesions,and the expression level increased with the increase of endometrial lesion level.The difference among the three groups was statistically significant(P<0.05).CA125 level was related to International Federation of Gynecology and Obstetrics(FIGO)stage,lymph node metastasis and ki-67 index.CA153 level was related to ki-67 index.CA199 was related to FIGO stage,tissue differentiation and lymph node metastasis.NLR was related to FIGO stage,pathological type,tissue differentiation,myometrial invasion and lymph node metastasis.PLR was correlated with tissue differentiation,and the differences were statistically significant(P<0.05).The diagnosis of NLR combined with CA was the largest area under ROC curve(0.940),and its accuracy,sensitivity and specificity were higher than those of individual parameters and NLR combined with CA.Conclusion:NLR,PLR,CA125,CA153 and CA199 were highly expressed in EC and were correlated with clinical pathological data of EC patients respectively.NLR and PLR combined with CA could significantly improve the diagnostic efficiency of EC,providing clinical reference value for EC screening,therapeutic effect evaluation and disease progression evaluation.