Endometrial Carcinoma Patients Research Articles

Early endometrial carcinoma: Experience and outcomes.

Endometrial carcinoma (EC) data from India are very sparse. We did a retrospective analysis of our patients registered at this peripheral cancer center based in rural Punjab and studied their outcome. Ninety-eight Stage I and II EC patients with endometroid histology registered at our institute from January 2015 to April 2020 were studied for demography, histopathology, treatment received, and outcomes. FIGO 2009 staging and new European Society for Medical Oncology (ESMO) risk group classification was used. Our patients had a median age of 60 years (range 32-93 years). There were 39 (39.8%), 41 (42.0%), 4 (4.1%), 12 (12.2%) patients in the low risk, intermediate risk (IR), high intermediate risk, and high risk groups, respectively, as per new ESMO risk classification. Two (2.0%) patients had incomplete information to assign them to a particular risk group. Fifty (46.7%) patients underwent complete surgical staging and 54 (50.5%) patients received adjuvant RT. With a median follow-up of 27.0 months, there were 1 locoregional and 2 distant recurrences. There were 8 deaths in total. Three-year overall survival for the entire group is 90.6%. The risk group determines adjuvant treatment in endometrial cancer. Patients operated at dedicated cancer center tend to have better surgical staging and thus better outcome because of better risk stratification and grouping for adjuvant therapy. IR histology was more common in our group of patients, which is variable as compared to available literature.

The clinicopathological characteristics of POLE-mutated/ultramutated endometrial carcinoma and prognostic value of POLE status: a meta-analysis based on 49 articles incorporating 12,120 patients

ObjectiveThis study was designed to investigate the frequency and clinicopathological characteristics of POLE-mutated/ultramutated (POLEmut) in endometrial carcinoma (EC) and assess the prognostic values of POLE status.MethodsElectronic databases were screened to identify relevant studies. Meta-analysis was used to yield the pooled frequency of POLEmut and prognostic parameters by 95% confidence interval (CI), odd ratio (OR), and hazard ratio (HR).ResultsTotally, 12,120 EC patients from 49 studies were included. The pooled frequency of POLEmut was 7.95% (95% CI: 6.52–9.51%) in EC, 7.95% (95% CI: 6.55–9.46%) in endometrioid endometrial carcinoma, and 4.45% (95% CI: 2.63–6.61%) in nonendometrioid endometrial carcinoma. A higher expression occurred in grade 3 (OR = 0.51, 95% CI: 0.36–0.73, P = 0.0002), FIGO stage I-II (OR = 1.91, 95% CI: 1.29–2.83, P = 0.0013), and myometrial invasion< 50% (OR = 0.66, 95% CI: 0.50–0.86, P = 0.0025). Survival analyses revealed favorable OS (HR = 0.68, 95% CI: 0.55–0.85, P = 0.0008), PFS (HR = 0.74, 95% CI: 0.59–0.93, P = 0.0085), DSS (HR = 0.61, 95% CI: 0.44–0.83, P = 0.0016), and RFS (HR = 0.47, 95% CI: 0.35–0.61, P < 0.0001) for POLEmut ECs. Additionally, the clinical outcomes of POLEmut group were the best, but those of p53-abnormal/mutated (p53abn) group were the worst, while those of microsatellite-instable (MSI)/hypermutated group and p53-wild-type (p53wt) group were medium.ConclusionsThe POLEmut emergered higher expression in ECs with grade 3, FIGO stage I-II, and myometrial invasion< 50%; it might serve as a highly favorable prognostic marker in EC; the clinical outcomes of POLEmut group were the best one among the four molecular subtypes.

Recurrence and Survival Rates of Patients Who Undergo Minimally Invasive Surgery for Endometrial Carcinoma with Different Prognostic Risk Groups

Objective To compare the recurrence rate and prognosis between minimally invasive surgical (MIS) approach and open surgical approach of endometrial carcinoma (EC) patients with different prognostic risk groups. Methods A retrospective analysis of all cases undergoing EC surgery between January 2011 and March 2018 was performed. The patients were grouped according to the management guidelines of EC patients jointly formulated by the ESGO/ESTRO/ESP 2020. Different surgical approaches were compared with regard to tumor characteristics, recurrence rate, disease-free survival (DFS), and overall survival (OS). Results A total of 665 patients met the inclusion criteria of which 196 patients underwent MIS (29.5%), and 469 patients underwent open surgery (70.5%). In the MIS group, there was a significant higher rate of recurrence (17.3% vs 6.6%, P = 0.000) compared to the open surgery group. The recurrence rate of MIS was 7.7% (P = 0.000) in the medium-high risk group and 8.2% (P = 0.014) in the high-risk group. Multivariate logistic regression analysis showed that the independent factors influencing recurrence included prognostic risk grouping, surgical approach and lymph vascular space invasion (LVSI) positivity (P < 0.05). K-M survival analysis revealed that in the intermediate and high-risk group of EC, MIS patients had a significantly lower DFS than those undergoing open surgery (P < 0.05), but no significant difference was found in OS. Conclusions For patients with EC at moderate and high prognostic risk, MIS is associated with poorer DFS compared to open surgery, but OS was similar across prognostic risk groups. The application of MIS in patients with moderate and high-risk EC needs further research and analysis.

7868 The Incidence of Endometrial Carcinoma in Patients with Atypical Endometrial Hyperplasia Versus Atypical Endometrial Polyp

<h3>Study Objective</h3> To compare the incidence of endometrial carcinoma following hysterectomy in patients with presurgical diagnosis of EIN (endometrial intraepithelial neoplasia) of the endometrium versus EIN confined to endometrial polyp. <h3>Design</h3> Retrospective cohort study. <h3>Setting</h3> Tertiary university-affiliated hospital. <h3>Patients or Participants</h3> Eighty-eight women included in the study, of those, 50 women were diagnosed with EIN confined to a polyp (endometrial polyp group) and 38 women had endometrial EIN following endometrial biopsy (non-polypoid group). <h3>Interventions</h3> Medical records of women who underwent staging surgery for endometrial EIN or EIN confined to a polyp between 2014 and 2020 were reviewed. <h3>Measurements and Main Results</h3> The mean age at diagnosis was 60.2 ± 9.9 years in the endometrial polyp group as compared to 61.7 ± 12 years in the non-polypoid group (p=0.5). Eighty-nine percent of the women in the non-polypoid group presented with abnormal uterine bleeding (post/perimenopausal) whereas 46% of the women in the endometrial polyp group were asymptomatic (p=0.001). Pathology results following hysterectomy revealed concurrent endometrial carcinoma in 26% of women in the endometrial polyp group compared to 47% of women in the non-polypoid group (p=0.001). Eighty-four percent of cancers were grade-1 in the endometrial polyp group compared to 50% in the non-polypoid group(p=0.048). Only one patient in the non-polypoid group (5.6%) had lymph node involvement. <h3>Conclusion</h3> Concurrent cancer is less frequent with atypical endometrial polyp as compared to atypical endometrial hyperplasia. Still, the high incidence of endometrial carcinoma in both groups supports the current advice to perform hysterectomy and bilateral salpingo-oophorectomy for peri and post-menopausal women. Our data does not support performing sentinel lymph node dissection for EIN.

Use of a Carbon Nanoparticle Tracer to Detect Sentinel Lymph Nodes for the Precise Treatment of Endometrial Carcinoma

We evaluated the usefulness of a carbon nanoparticle (CNP) tracer for the detection of sentinel lymph nodes (SLNs) for the precise treatment of endometrial carcinoma (EC). Among patients who presented at First Affiliated Hospital, College of Medicine, Zhejiang University, and Xiangshan First People’s Hospital Medical and Health Group between February 2019 and February 2022, we selected 90 patients who required surgical treatment for EC. During the operation, CNP was injected into the cervix by the two-point method, and black-stained LNs were identified as SLNs and resected. Then, statistical analyses were conducted to evaluate SLN occurrence area, CNP traceability, SLN detection rate, as well as diagnostic data such as false negative rate (FNR), sensitivity (SEN), specificity (SPE), positive/negative predictive value (PPV/NPV), and accuracy (ACC). CNP tracing detected SLN mainly at the external iliac (45.09%) and obturator (36.36%) regions. CNP tracing of SLNs was successful in 80 patients, with an SLN detection rate of 88.89%. Eight cases (10.00%) were positive for SLNs, with an FNR of 12.50%. The SEN, SPE, PPV, NPV, and ACC values for CNP detection of SLNs were 87.50%, 98.78%, 87.50%, 98.78%, and 97.78%, respectively. Our results indicate that CNP is an effective tracer for SLNs. When operating on EC patients, CNP tracing of SLNs can help to judge lymph node metastasis and regional distribution, providing a reliable basis for the determination of surgical scope.

OTUB2 promotes the progression of endometrial cancer by regulating the PKM2-mediated PI3K/AKT signaling pathway.

Endometrial carcinoma (EC) morbidity and mortality have been increasing in recent years. Otubain 2 (OTUB2) was shown to be upregulated in EC patients, so the aim of this study was to explore the role of OTUB2 in EC. Cell Counting Kit-8 (CCK-8), colony formation, enzyme-linked immunosorbent assay, the wound healing assay, and Transwell invasion assays were used to investigate the specific role of OTUB2 in EC tumorigenesis.Real-timepolymerase chain reaction andwestern blot analysis were used to detect the expression of OTUB2 in EC tissues and cells. OTUB2 is upregulated in EC patients and cell lines and is associated with a poor prognosis. The overexpression of OTUB2 promoted glycolysis and induced the proliferation, migration, and invasion of endometrial cancer cells. The silencing of OTUB2 had the opposite effect. In addition, the silencing of OTUB2 significantly suppressed the expression levels of PKM2. Importantly, inhibition of the PKM2/PI3K/AKT signaling pathway significantly reversed the promoting effect of OTUB2 overexpression on EC. OTUB2 regulated the proliferation and invasion of EC cells by regulating the PKM2/PI3K/AKT signaling pathway. OTUB2 may serve as a potential prognostic and therapeutic target in EC.

Molecular classification and clinicopathological features of endometrial carcinoma

Objective: To investigate the molecular classification and clinicopathological features of endometrial carcinoma(EC). Methods: One hundred cases of EC diagnosed in the Department of Pathology, Tianjin Central Hospital of Gynecology and Obstetrics from November 2020 to November 2021 were selected. Sanger sequencing and immunohistochemical staining were used for molecular classification according to the 5th WHO classification. The clinicopathological characteristics of each molecular subtype was analyzed. Results: The 100 EC patients had a mean age of 53 years (range 26 to 72 years). There were 10 cases of POLE mutation (POLE mut), including two cases (2/10) of "binary-classifier" EC, two cases (2/10) of FIGO Grade 3 endometrioid endometrial carcinoma (G3-EEC), and three cases (3/10) of other high-grade subtypes. There were 38 cases of mismatch repair deficiency (dMMR), including one case (1/38, 2.6%) of "binary-classifier" EC and 36 cases (36/38, 94.7%) were EEC. Twenty-one cases (21/38, 55.3%) showed simultaneous loss of expression of MLH1 and PMS2, and 20 cases (20/21, 95.2%) were positive for MLH1 methylation, indicating that they were sporadic EC. Six patients (6/38, 15.8%) were tested for germline detection of Lynch syndrome (LS) related genes, and one patient was LS-related EC. There were 44 cases of non-specific molecular profile (NSMP), including 34 cases (34/44, 77.3%) of G1-2 EEC and seven cases (7/44, 15.9%) of G3-EEC. There were eight cases of p53 abnormality (p53 abn), including four cases (4/8) of G3-EEC, two cases (2/8) of other high-grade subtypes, and one patient had hereditary breast cancer and ovarian cancer syndrome. Conclusions: Correct interpretation of POLE mutation, MMR and p53 immunohistochemistry is the key of molecular classification. The interpretation must strictly follow standard diagnostic procedures and specifications to ensure the accuracy of molecular classification.

Loss of LOXL2 Promotes Uterine Hypertrophy and Tumor Progression by Enhancing H3K36ac-Dependent Gene Expression.

LOXL2 loss reprograms the epigenetic landscape to promote uterine cancer initiation and progression and repress the efficacy of anti-PD-1 immunotherapy, indicating that LOXL2 is a tumor suppressor.

Comprehensive landscape of the functions and prognostic value of RNA binding proteins in uterine corpus endometrial carcinoma.

Background: The dysregulation of RNA binding proteins (RBPs) is involved in tumorigenesis and progression. However, information on the overall function of RNA binding proteins in Uterine Corpus Endometrial Carcinoma (UCEC) remains to be studied. This study aimed to explore Uterine Corpus Endometrial Carcinoma-associated molecular mechanisms and develop an RNA-binding protein-associated prognostic model. Methods: Differently expressed RNA binding proteins were identified between Uterine Corpus Endometrial Carcinoma tumor tissues and normal tissues by R packages (DESeq2, edgeR) from The Cancer Genome Atlas (TCGA) database. Hub RBPs were subsequently identified by univariate and multivariate Cox regression analyses. The cBioPortal platform, R packages (ggplot2), Human Protein Atlas (HPA), and TIMER online database were used to explore the molecular mechanisms of Uterine Corpus Endometrial Carcinoma. Kaplan-Meier (K-M), Area Under Curve (AUC), and the consistency index (c-index) were used to test the performance of our model. Results: We identified 128 differently expressed RNA binding proteins between Uterine Corpus Endometrial Carcinoma tumor tissues and normal tissues. Seven RNA binding proteins genes (NOP10, RBPMS, ATXN1, SBDS, POP5, CD3EAP, ZC3H12C) were screened as prognostic hub genes and used to construct a prognostic model. Such a model may be able to predict patient prognosis and acquire the best possible treatment. Further analysis indicated that, based on our model, the patients in the high-risk subgroup had poor overall survival (OS) compared to those in the low-risk subgroup. We also established a nomogram based on seven RNA binding proteins. This nomogram could inform individualized diagnostic and therapeutic strategies for Uterine Corpus Endometrial Carcinoma. Conclusion: Our work focused on systematically analyzing a large cohort of Uterine Corpus Endometrial Carcinoma patients in the The Cancer Genome Atlas database. We subsequently constructed a robust prognostic model based on seven RNA binding proteins that may soon inform individualized diagnosis and treatment.

Nuclear Expression of β-Catenin Is Associated with Improved Outcomes in Endometrial Cancer.

Beta-catenin is involved in intercellular adhesion and participates in the Wnt signaling pathway. This study evaluated the expression pattern and prognostic value of β-catenin in a series of endometrial carcinoma patients. Immunohistochemical analyses were used to assess the expression and subcellular localization of β-catenin from tissue sections of 74 patients with endometrial carcinoma. No correlation was found between beta-catenin expression and clinicopathological parameters. Patients expressing nuclear β-catenin (n = 13; 16%) showed a more favorable prognosis than patients expressing membranous β-catenin; the 5-year disease-related survival rate was 100% for cases expressing nuclear β-catenin, compared with 73.8% (SE 0.08) of cases expressing membranous β-catenin (p = 0.04). Although statistical significance was not reached (p = 0.15), cases expressing nuclear β-catenin showed a 5-year disease-free survival rate of 90.9% (SE 0.08) compared with 67.4% (SE 0.08) of cases expressing membranous β-catenin. Univariate Cox analysis revealed that membranous β-catenin expression was found to be associated with a relative risk of death of 33.9 (p = 0.04). The stage of disease (p = 0.0006), histology (p = 0.003), and grading (p = 0.008) were also significantly correlated with disease-free survival according to univariate Cox analyses. Determining β-catenin expression and localization patterns may predict survival in patients with endometrial cancer and, therefore, should be considered a potential prognostic marker of disease.

Mechanisms of mutant β-catenin in endometrial cancer progression.

Endometrial carcinoma (EC) is the most diagnosed gynecological malignancy in Western countries. Both incidence and mortality rates of EC have steadily risen in recent years. Despite generally favorable prognoses for patients with the endometrioid type of EC, a subset of patients has been identified with decreased progression-free survival. Patients in this group are distinguished from other endometrioid EC patients by the presence of exon 3 hotspot mutations in CTNNB1, the gene encoding for the β-catenin protein. β-catenin is an evolutionarily conserved protein with critical functions in both adherens junctions and Wnt-signaling. The exact mechanism by which exon 3 CTNNB1 mutations drive EC progression is not well understood. Further, the potential contribution of mutant β-catenin to adherens junctions’ integrity is not known. Additionally, the magnitude of worsened progression-free survival in patients with CTNNB1 mutations is context dependent, and therefore the importance of this subset of patients can be obscured by improper categorization. This review will examine the history and functions of β-catenin, how these functions may change and drive EC progression in CTNNB1 mutant patients, and the importance of this patient group in the broader context of the disease.

Significance of molecular classification in fertility-sparing treatment of endometrial carcinoma and atypical endometrial hyperplasia

Objective: To investigate the molecular classification of endometrial carcinoma (EC) and atypical endometrial hyperplasia (AEH) treated with fertility-sparing therapy, and to analyze its relationship with clinicopathological factors and treatment efficacy. Methods: A total of 46 EC and AEH patients who received fertility-sparing therapy and molecular classification tested by next generation sequencing in Peking University People's Hospital from June 2020 to December 2021, were retrospectively collected. The relationships between molecular classification and clinicopathological factors and treatment outcomes were analyzed. Results: (1) Of the 46 patients, including 40 EC and 6 AEH patients, 32 cases (71%, 32/45) had complete response (CR) after treatment, with median CR time of 8 months, 6 cases (13%, 6/45) had partial response, and 8 cases (25%, 8/32) had recurrence. (2) The cases were distributed as no specific molecular profile (NSMP) 34 cases (74%, 34/46) subtype mainly, high microsatellite instability (MSI-H) 7 cases (15%, 7/46), POLE ultra-mutated 3 cases (7%, 3/46), and copy number high (CNH) 2 cases (4%, 2/46). Patients with CNH had the hightest serum cancer antigen 125 (CA125) level [(34.3±35.2) kU/L]. MSI-H subtype had more family history of tumors (6/7), more with loss of mismatch repair (MMR) protein expression by immunohistochemical (7/7), and higher nuclear antigen associated with cell proliferation (Ki-67) expression level (3/3). (3) Patients in MSI-H subgroup had the lowest CR rate at 6 months (0/6; P=0.019), and survival analysis showed that they were less likely to achieve CR than those with NSMP subtype (P=0.022). Subgroup analysis of patients with NSMP showed that age ≥30 years related with longer treatment time to CR (P=0.010). In addition, CR was obtained after treatment in 2/3 POLE ultra-mutated cases and 2/2 CNH, respectively. Conclusions: Molecular classification relates with the treatment response in patients with EC and AEH treated with fertility-sparing therapy. Patients with MSI-H subtype have poor treatment efficacy, and patients with NSMP need to be further studied and predict treatment benefit. However, there are few cases in POLE ultra-mutated and CNH subtypes, which need further clinical research.

Is preoperative ultrasound tumor size a prognostic factor in endometrial carcinoma patients?

ObjectiveWe aimed to assess the prognostic value of preoperative ultrasound tumor size in EC through a single center, observational, retrospective, cohort study.MethodsMedical records and electronic clinical databases were searched for all consecutive patients with EC, preoperative ultrasound scans available to ad hoc estimate tumor size, and a follow-up of at least 2-year, at our Institution from January 2010 to June 2018. Patients were divided into two groups based on different dimensional cut-offs for the maximum tumor diameter: 2, 3 and 4 cm. Differences in overall survival (OS), disease specific survival (DSS) and progression-free survival (PFS) were assessed among the groups by using the Kaplan–Meier estimator and the log-rank test.Results108 patients were included in the study. OS, DSS and PFS did not significantly differ between the groups based on the different tumor diameter cut-offs. No significant differences were found among the groups sub-stratified by age, BMI, FIGO stage, FIGO grade, lymphovascular space invasion status, myometrial invasion, lymph nodal involvement, histotype, and adjuvant treatment.ConclusionsPreoperative ultrasound tumor size does not appear as a prognostic factor in EC women.

Prognosis and Efficacy of Laparoscopic Surgery on Patients with Endometrial Carcinoma: Systematic Evaluation and Meta-Analysis.

Objective The prognosis and efficacy of laparoscopic surgery (LPS) and open surgery or robotic surgery (RS) on endometrial carcinoma (EC) patients were compared. Methods Data as of May 2021 were retrieved from databases like PubMed, Embase, Cochrane Library, and Web of Science. The study involved randomized controlled trials (RCTs), cohort studies, or case-control studies for comparing the effects of LPS and open surgery or robotic surgery (RS) on EC treatment. The primary outcomes included duration of operation, blood loss, length of stay (LOS), postoperative complications, and recurrence rate. Secondary outcomes included 3-year progression-free survival (PFS) rate/disease-free survival (DFS) rate and 3-year overall survival (OS) rate. Results A total of 24 studies were involved, and all of them were cohort studies except 1 RCT and 1 case-control study. There was no significant difference in duration of operation between LPS and open surgery (MD = −0.06, 95% CI: -0.37 to 0.25) or RS (MD = −0.15, 95% CI: -1.27 to 0.96). In comparison with the open surgery, LPS remarkably reduced blood loss (MD = −0.43, 95% CI: -0.58 to -0.29), LOS (MD = −0.71, 95% CI: -0.92 to -0.50), and the complication occurrence rate (RR = 0.83, 95% CI: 0.73 to 0.95). However, LPS and RS saw no difference in blood loss (MD = 0.01, 95% CI: -0.77 to 0.79). Besides, in comparison with RS, LPS prominently shortened the LOS (MD = 0.26, 95% CI: 0.12 to 0.40) but increased the complication occurrence rate (RR = 1.74, 95% CI: 1.57 to 1.92). In contrast to open surgery or RS, LPS saw no difference in occurrence rate (RR = 0.75, 95% CI: 0.56 to 1.01; RR = 0.97, 95% CI: 0.62 to 1.53), 3-year PFS/DFS (RR = 0.99, 95% CI: 0.90 to 1.09; RR = 1.30, 95% CI: 0.87 to 1.96), and 3-year OS (RR = 0.97, 95% CI: 0.91 to 1.04; RR = 1.21, 95% CI: 0.91 to 1.60). Conclusion In sum, LPS was better than open surgery, which manifested in the aspects of less blood loss, shorter LOS, and fewer complications. LPS, therefore, was the most suitable option for EC patients. Nevertheless, LPS had no advantage over RS, and sufficient prospective RCTs are needed to further confirm its strengths.

A comprehensive analysis of G-protein-signaling modulator 2 as a prognostic and diagnostic marker for pan-cancer.

Background: G-protein signaling modulator 2 (GPSM2) maintains cell polarization and regulates the cell cycle. Recent studies have shown that it is highly expressed in various tumors, but its pan-cancer analysis has not been reported. Methods: First, we analyzed the differential GPSM2 expression in normal and cancer tissues by the Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx) and Human Protein Atlas databases and investigated its expression effect on the survival of cancer patients by gene expression profiling interactive analysis 2 (GEPIA2). Second, we analyzed the GPSM2 phosphorylation level using the clinical proteomic tumor analysis consortium dataset. In addition, we investigated GPSM2 gene mutations in human tumor specimens and the impact of gene mutations on patient survival. Finally, we analyzed the relationship between GPSM2 expression and cellular immune infiltration through the TIMER 2.0 database. Meanwhile, the possible signaling pathway of the gene was analyzed by the Gene Ontology (GO)| Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway to explore its potential mechanism. Results: GPSM2 is overexpressed in most cancers, which leads to reduced overall survival (OS) and disease-free survival in patients. The results of phosphorylation analysis suggest that tumor development involves a complex GPSM2 phosphorylation process. We identified GPSM2 mutation loci with the highest frequency of mutations in uterine corpus endometrial carcinoma (UCEC), and this mutation increased progression-free survival and overall survival in uterine corpus endometrial carcinoma patients. Finally, we found that the role of GPSM2 in tumors may be associated with cellular immune infiltration. Gene Ontology|KEGG pathway analysis showed that the enrichment pathways were mainly “mitotic nuclear division,” “chromosome segregation,” and “spindle.” Conclusions: Our pan-cancer analysis provides a comprehensive overview of the oncogenic roles and potential mechanisms of GPSM2 in multiple human cancers.

Tripartite Motif Containing 26 is a Positive Predictor for Endometrial Carcinoma Patients and Regulates Cell Survival in Endometrial Carcinoma.

Functioning as an E3 ubiquitin ligase, tripartite motif containing 26 (TRIM26) can regulate the tumor behavior and the relevant inflammatory immune response. Endometrial carcinoma is a major gynecological malignant tumor in the world, while no relevant research has been performed. KMplot, a web-based survival analysis tool, demonstrated that TRIM26 expression was positively correlated with the overall survival in gynecological tumors, such as ovarian, cervical, and endometrial cancer. The relatively low expression of TRIM26 was also found in endometrial cancer tissues and endometrial cancer cell lines. In the online Gene Expression Profiling Interactive Analysis (GEPIA) platform, TRIM26 was positively correlated with the pre-apoptosis genes of p53, BIM, BID, BAX, and BAK, and negatively correlated with the anti-apoptosis gene of BCLW. To further explore the function of TRIM26 in endometrial carcinoma, Ishikawa and KLE cells were infected with PLVX-TRIM26-derived lentivirus. TRIM26 overexpression suppressed the growth of endometrial cells, with downregulated p-AKT and upregulated BIM and BID expression. PLVX-TRIM26 overexpressed Ishikawa cells were injected subcutaneously into the side flanks of male BALB/C nude mice to construct a TRIM26-overexpression xenograft model. TRIM26 overexpression suppressed the growth of endometrial cancer as indicated by downregulated tumor volume and tumor weight with downregulated p-AKT expression. TRIM26 could regulate AKT pathway and apoptosis process to inhibit the growth of endometrial carcinoma, which can be utilized as a survival predictor.

Multifaceted investigation underlies diverse mechanisms contributing to the downregulation of Hedgehog pathway-associated genes INTU and IFT88 in lung adenocarcinoma and uterine corpus endometrial carcinoma.

Hedgehog (Hh) signaling primarily functions in the control of mammalian embryonic development but also has roles in cancer. The Hh activation depends on ciliogenesis, a cellular process that describes outgrowth of the primary cilium from cell membrane. Ciliogenesis initiation requires a set of proteins known as planar cell polarity (PCP) effectors. Inturned (INTU) is a PCP effector that reportedly functions synergistically with Hh signaling in basal cell carcinoma, suggesting that INTU has an oncogenic role. In this study, we carried out a pan-cancer investigation on the prognostic significance of INTU in different types of cancer. We demonstrated that INTU downregulation correlated with reduced survival probabilities in lung adenocarcinoma (LUAD) and uterine corpus endometrial carcinoma (UCEC) patients. Similar expression patterns and prognostic values were identified for intraflagellar transport 88 (IFT88), another Hh pathway-associated gene. We elucidated multiple mechanisms at transcriptional, post-transcriptional and translational levels that involved transcription factor 4 and non-coding RNAs-associated regulatory networks contributing to the reduction of INTU and IFT88 levels in LUAD and UCEC samples. Taken together, this study demonstrates the prognostic significance of the Hh-related genes INTU and IFT88 in LUAD and UCEC and further delineates multifaceted mechanisms leading to INTU and IFT88 downregulation in tumor samples.

COVID-19-associated lncRNAs as predictors of survival in uterine corpus endometrial carcinoma: A prognostic model.

Background: Patients with uterine corpus endometrial carcinoma (UCEC) may be susceptible to the coronavirus disease-2019 (COVID-19). Long non–coding RNAs take on a critical significance in UCEC occurrence, development, and prognosis. Accordingly, this study aimed to develop a novel model related to COVID-19–related lncRNAs for optimizing the prognosis of endometrial carcinoma. Methods: The samples of endometrial carcinoma patients and the relevant clinical data were acquired in the Carcinoma Genome Atlas (TCGA) database. COVID-19–related lncRNAs were analyzed and obtained by coexpression. Univariate, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analyses were performed to establish a COVID-19–related lncRNA risk model. Kaplan–Meier analysis, principal component analysis (PCA), and functional enrichment annotation were used to analyze the risk model. Finally, the potential immunotherapeutic signatures and drug sensitivity prediction targeting this model were also discussed. Results: The risk model comprising 10 COVID-19–associated lncRNAs was identified as a predictive ability for overall survival (OS) in UCEC patients. PCA analysis confirmed a reliable clustering ability of the risk model. By regrouping the patients with this model, different clinic-pathological characteristics, immunotherapeutic response, and chemotherapeutics sensitivity were also observed in different groups. Conclusion: This risk model was developed based on COVID-19–associated lncRNAs which would be conducive to the precise treatment of patients with UCEC.

Metabolic syndrome is an independent risk factor for time to complete remission of fertility-sparing treatment in atypical endometrial hyperplasia and early endometrial carcinoma patients

ObjectiveFertility-sparing treatment of atypical endometrial hyperplasia (AEH) and early endometrial carcinoma (EC) patients has recently emerged important social health topic. This study is designed to explore the risk factors for time to complete remission (CR) of fertility-sparing treatment in woman with AEH and early EC.MethodsA retrospective study was designed with clinical data from 106 patients admitted between January 2012 to December 2019. Univariate and multivariate logistic analysis were used to explore independent risk factors for time to CR. These factors were employed in receiver operator characteristic (ROC) curve and the decision curve analysis (DCA) to evaluate predictive accuracy of time to CR. Stratified analysis and interactive analysis was also performed for more in-depth perspective.ResultsUnivariate analysis showed that fasting blood glucose levels (FBG, OR = 1.6, 95%CI: 0.6–2.5, P = 0.020), metabolic syndrome (MetS, OR = 3.0, 95%CI: 1.1–5.0, P = 0.003), and polycystic ovary syndrome (PCOS, OR = 2.0, 95%CI: 0.5–3.4, P = 0.009) were associated with time to CR. Among these factors, multivariate analysis confirmed MetS (OR = 3.1, 95%CI: 1.0–5.2, P = 0.005) was an independent risk factor. The area under the ROC curve (AUC) of MetS was higher than FBG and PCOS (AUC = 0.723 vs 0.612 and 0.692). The AUC of FBG combined with PCOS was 0.779, and it was improved to 0.840 when MetS was included (P < 0.05). Additionally, MetS played different roles in time to CR in various groups. Moreover, we found high-density lipoprotein (HDL) and MetS had an interactive effect for time to CR.ConclusionMetS is an independent risk factor for time to CR and should be taken seriously in fertility-sparing management of AEH and early EC patients.

LncRNA TUG1 promotes the migration and invasion in type I endometrial carcinoma cells by regulating E–N cadherin switch

ObjectiveAccumulating evidence has demonstrated that lncRNA Taurine-upregulated gene 1 (TUG1) plays an important role in regulation of cell morphology, migration, proliferation and apoptosis. Our aim was to evaluate the oncogenic role of TUG1 in type I Endometrial Carcinoma (EC) and explore the precise mechanism of TUG1 involved in tumor progression. Materials and methodsThe GSE17025 data set was used to analyze the correlation of TUG1 expression with type I EC patients’ prognosis. Furthermore, TUG1 expression profiles were measured by qRT-PCR from carcinoma tissues and adjacent nonneoplastic tissues (NNT) of 105 type I EC patients. The regulation of epithelial–mesenchymal transition (EMT) related molecules, p-AKT and AKT by TUG1 knockdown was investigated using Western blot analysis; meanwhile, the oncogenic roles of TUG1 were evaluated using cell viability and transwell migration/invasion assay in Hec-1-A and Ishikawa cell lines. ResultsFirstly, we observed a significant association between higher TUG1 expression and lower survival rate in type I EC patients using the GSE17025 data set. A significant elevation of TUG1 levels was confirmed in type I EC tissues compared with NNT in the 105 type I EC patients, and high expression of TUG1 was associated with lymph vascular space invasion (LVSI) and lymph node metastasis (LNM). Subsequently, TUG1 knockdown could remarkably inhibit the Hec-1-A and Ishikawa cell invasion and migration in the functional experiment. Furthermore, our results showed that the protein levels of E-cadherin increased and N-cadherin decreased significantly, while β-catenin and Vimentin were not significantly altered upon TUG1 silencing in both Hec-1-A and Ishikawa cells. Finally, we found the p-AKT and AKT protein levels, and the rate of p-AKT/t-AKT has a tendency to be down-regulate in Hec-1-A cells, while the AKT pathway was not change significantly in Ishikawa cells after TUG1 knockdown. ConclusionCollectively, our data reveal that TUG1 might be regarded as an oncogenic molecule that promotes type I EC cells metastasis leading to tumor progression, at least partially, by regulating E–N cadherin switch and the AKT pathway.