Background: Endometrial cancer (EC) is a common gynecological malignancy with increasing incidence. While several serum biomarkers have been studied for EC, their combined prognostic value remains unclear. This study aimed to evaluate the prognostic significance of preoperative serum CA125, CA19-9, CA72-4, CEA, and AFP levels in EC patients and develop a risk score for predicting survival outcomes. Methods: A retrospective cohort study of 2,081 EC patients was conducted at Shengjing Hospital of China Medical University. Serum biomarker levels and clinicopathological data were collected. Univariate and multivariate Cox proportional hazard models were used to identify independent prognostic factors. A risk score based on CA125, CEA, and AFP levels was developed using LASSO-Cox regression, and nomograms were constructed for survival prediction. Results: Multivariate analysis identified elevated CA125 (P=0.003), AFP (P<0.0001), and CEA (P=0.014) as independent factors for overall survival (OS). These markers were also independent predictors of progression-free survival (PFS). The risk score incorporating CA125, AFP, and CEA was an independent indicator for both PFS (P<0.0001) and OS (P<0.0001). Nomograms based on the risk score and clinicopathological features demonstrated good predictive ability and calibration for survival outcomes. Conclusions: The risk score based on preoperative serum levels of CA125, CEA, and AFP is a valuable prognostic tool for predicting PFS and OS in EC patients. Nomograms incorporating this risk score accurately predict EC prognosis and may aid in clinical decision-making. Funding: This study was supported by the National Key R&D Program of China (Program Nos. 2022YFC2704400, The National Natural Science Foundation of China (No. 81872123 and 81472438); University innovation team of Liaoning Province; Special Professor of Liaoning Province 'Major Special Construction Plan' for Discipline Construction of China Medical University in 2018 (No. 3110118029); Outstanding Scientific Fund of Shengjing Hospital(No. 201601) 'Major Special Construction Plan' for Discipline Construction of China Medical University in 2018.

Endometrial cancer (EC), a leading gynecological malignancy, exhibits heterogeneous progression and limited predictive biomarkers for personalized management. Stratifin (SFN), a cell-cycle regulatory protein, has been implicated in oncogenesis, but its role in EC progression and prognosis remains undefined. This study integrates multi-omics, immunohistochemistry, and survival modeling to establish Stratifin as a novel biomarker for EC. Differentially expressed genes (DEGs) in uterine corpus endometrial cancer (UCEC) were identified by meta-analysis of GSE17025 (n = 147 UCEC vs. 14 normal) and GSE63678 (n = 150 UCEC vs. 10 normal) datasets using limma-voom (FDR < 0.05, |log₂FC| >1). Protein-protein interaction (PPI) networks were constructed via STRING (confidence score > 0.7) and visualized in Cytoscape, with densely connected modules identified using the MCODE plugin (MCODE score > 5). Kaplan-Meier survival curves and log-rank tests were performed on TCGA-UCEC data (n = 586) to evaluate associations between hub gene expression and overall survival (OS). Immunohistochemical (IHC) staining for Stratifin was conducted on tissue microarrays containing 36 normal endometrium, 37 atypical hyperplasia, and 104 endometrioid endometrial carcinoma (EEC) samples, scored by intensity (0–3) and proportion (0–100

M2 macrophages are known to be involved in tumorigenesis. However, the mechanism by which they promote tumor progression in endometrial cancer (EC) remains largely unknown. Kynureninase (KYNU) has been found to be associated with the progression of various tumors, but research on endometrium is limited to embryo transfer. Therefore, a better understanding of KYNU as a potential therapeutic target in EC treatment is needed. This study aimed to elucidate the mechanism by which M2 macrophage-secreted KYNU influences the malignant biological and stemness remodeling of EC via the SOD2-mtROS-ERO1α and endoplasmic reticulum unfolded protein response (UPRER) pathway. We used flow cytometry for cell sorting. Fluorescence experiments were conducted to reveal spatial position of protein, and. Western blot and qRT‒PCR were used to detect the protein and mRNA levels, respectively. The interaction between KYNU and superoxide dismutase 2 (SOD2) was demonstrated using coimmunoprecipitation experiments. Furthermore, the mechanism between activating transcription factor 4 (ATF4) and the KYNU was assessed using chromatin immunoprecipitation and dual luciferase assays. Cell Counting Kit-8, flow cytometry, and transwell assays were used to detect tumor cell proliferation, apoptosis, and invasion capacities. Student’s t test and one-way analysis of variance (ANOVA) were used to compare groups. M2 macrophage-secreted KYNU induced malignant behavior and stemness via the SOD2-mtROS-ERO1α-UPRER pathway, contributing to a positive feedback loop for tumor cell self-protection. Mechanistically, KYNU and its metabolite 3-hydroxyanthranillic acid (3-HAA) upregulated the expression of SOD2, thereby decreasing mitochondrial reactive oxygen species (mtROS). KYNU inhibitors affected the spatial overflow of mtROS from mitochondria to the endoplasmic reticulum (ER). Endoplasmic reticulum oxidoreductin 1α (ERO1α) was sensitively affected by KYNU-induced changes in the redox environment, stimulating the PERK-eIF2α-ATF4 pathway of the UPRER. This in turn promoted oxidative folding, reduced the level of misfolded protein (MFP), and maintained tumor survival and progression. Additionally, ATF4 acted as a transcription factor in the KYNU promoter region, amplifying KYNU tumorigenesis in a positive feedback manner. M2-secreted KYNU promotes the malignant behavior and stemness remodeling of EC via the SOD2-mtROS-ERO1α-UPRER axis and establishes a positive feedback loop. Thus, KYNU is a potential therapeutic target for EC treatment.

AbstractAs a hallmark of cancer, metabolic reprogramming adjusts macromolecular synthesis, energy metabolism and redox homeostasis processes to adapt to and promote the complex biological processes of abnormal growth and proliferation. The complexity of metabolic reprogramming lies in its precise regulation by multiple levels and factors, including the interplay of multiple signalling pathways, precise regulation of transcription factors and dynamic adjustments in metabolic enzyme activity. In this complex regulatory network, acetylation and deacetylation, which are important post‐translational modifications, regulate key molecules and processes related to metabolic reprogramming by affecting protein function and stability. Dysregulation of acetylation and deacetylation may alter cancer cell metabolic patterns by affecting signalling pathways, transcription factors and metabolic enzyme activity related to metabolic reprogramming, increasing the susceptibility to rapid proliferation and survival. In this review, we focus on discussing how acetylation and deacetylation regulate cancer metabolism, thereby highlighting the central role of these post‐translational modifications in metabolic reprogramming, and hoping to provide strong support for the development of novel cancer treatment strategies.Key points Protein acetylation and deacetylation are key regulators of metabolic reprogramming in tumour cells. These modifications influence signalling pathways critical for tumour metabolism. They modulate the activity of transcription factors that drive gene expression changes. Metabolic enzymes are also affected, altering cellular metabolism to support tumour growth.

The human endometrium is a vital component of the female reproductive system that is essential for fertilization, embryo development and female health. However, due to significant ethical concerns and practical limitations associated with human subject research and species differences in animal models, it is highly required to develop in vitro biomimetic human models to facilitate the understanding of physiology and pathology of endometrium in biomedical research. In this review, we highlight recent progress in bioengineered technologies, including organs-on-chips, organoids, advanced biomaterials and bioprinting that enable the reconstruction of functional endometrial models in vitro. We summarize various bioengineering strategies developed to recapitulate key features of the human endometrium in both healthy and diseased states. Furthermore, we introduce the application of these in vitro models in studies of reproductive biology, pregnancy processes and disease mechanisms. Finally, we discuss current challenges and future opportunities in the development of more sophisticated in vitro human endometrial models for biomedical research.

Correct immunological dialogue between the maternal uterus and conceptus is essential during implantation, and Toll-like receptors (TLRs) participate in maternal immune tolerance during pregnancy. This study aimed to analyze the effect of early pregnancy on Toll-like receptor pathways in the ovine endometrium. Ovine endometria were obtained on day 16 of the estrous cycle (N16) and days 13, 16, and 25 of pregnancy (P13, P16, and P25), and expression profiles of TLR members, including TLRs, tumor necrosis factor receptor-associated factor 6 (TRAF6), interleukin 1 receptor-associated kinase 1 (IRAK1), and myeloid differentiation primary response gene 88 (MyD88), were detected by quantitative real-time PCR, Western blot analysis, and immunohistochemistry analysis. The data of this study showed that the expression of TLR2 and TLR5 was gradually increased during early pregnancy compared to N16, and TLR3 expression was greater at P16 and P25 than at N16 and P13. However, the expression levels of TLR4 and TRAF6 were weaker at P13 and P16, and the expression of MyD88 was inhibited by early pregnancy. Furthermore, early pregnancy regulated IRAK1 expression. These findings corroborated that the TLR pathway was modulated in the ovine endometrium during early pregnancy, which may be involved in maternal immunoregulation.

The mammary glands are closely related to the female reproductive system. Due to various factors including increased survival of patients with breast cancer (BC), there is an increased probability of developing additional primary gynecologic cancers such as ovarian cancer (OC), endometrial cancer (EC), and cervical cancer (CC). Multiple primary cancers (MPCs) refer to two or more different primary malignancies occurring in the same or different organs in the same patient. This review discusses the common types of BC-associated MPCs, namely, BC associated with OC, EC, or CC, as well as risk factors, clinical classifications, pathology, treatment, and prognosis.

Disulfidptosis, a novel cell death paradigm triggered by disulfide stress, remains underexplored, particularly its implications for endometrial cancer (EC). This study focused on the prognostic significance of disulfidptosis-related genes (DRGs) in EC, highlighting the pivotal role of SLC3A2. To predict EC patient outcomes, we developed a model centered on DRGs, employing LASSO-Cox regression for its construction. The model revealed a strong correlation between DRG risk score, gene set enrichment analysis (GSEA), single-sample GSEA (ssGSEA), clinical characteristics, the tumor microenvironment (TME), and the response to immunotherapy. Key genes were pinpointed using random forest maps. To establish SLC3A2's oncogenic effects in EC, we conducted comprehensive studies including apoptosis, cell cycle, TRANSWELL, CCK-8, and tumor xenograft assays. SLC3A2 expression was further confirmed via qRT-PCR. The impact of SLC3A2 on EC's malignant behavior was corroborated through both in vitro and in vivo experiments.

Objective To determine preoperative serum CA125, CA19-9, CA72-4, CEA, and AFP with prognostic value, and to establish a risk score based on CA125, CEA, AFP levels for predicting the overall survival (OS) and progression-free survival (PFS) of endometrial cancer (EC) patients.Methods A retrospective cohort study with 2081 EC patients was conducted at Shengjing Hospital of China Medical University. Patient baseline information, tumor characteristics, and data on five serum biomarkers (CA125, CA19-9, CA72-4, CEA, and AFP) were collected. Hazard ratios (HRs) and 95% confidence intervals (CIs) were determined using univariate or multivariate Cox proportional hazard models. log-rank test and Kaplan-Meier analysis were used to compared survival, Data were randomly divided into a training cohort (50%, N = 1041) and an external validation cohort (50%, n = 1040). the least absolute shrinkage and selection operator (Lasso)-Cox regression model was used to screen the independent factors for establishing risk score. And develop nomograms for survival rate prediction.Results Multivariate analysis showed Elevated CA125 (P<0.0001) AFP (P <0.0001) and CEA(P=0.037) were identified as independent biomarkers for PFS. Increased CA125 (P = 0.003) AFP (P <0.0001) and CEA(P=0.014) were independent factors associated with OS. CA125, AFP and CEA were thus incorporated in an innovative Risk score (RS) by Lasso-Cox regression model, The RS was also an independent indicator for PFS (P<0.0001) and OS (P<0.0001). Furthermore, we developed and validated nomogram based on Cox regression models. The discriminative ability and calibration of the nomograms revealed good predictive ability, as indicated by the calibration plots.Conclusion This study suggests that the risk score based on preoperative serum levels of CA125, CEA, and AFP was prognostic biomarkers for predicting progression-free survival and overall survival for EC patients. Nomograms based on the RS and clinicopathological features accurately predict Prognosis of EC patients.### Competing Interest StatementThe authors have declared no competing interest.* EC : endometrial cancer OS : overall survival PFS : progression-free survival FIGO : International Federation of Gynecology and Obstetrics CA125 : carbohydrate antigen 125 CA19-9 : carbohydrate antigen 19-9 CA72-4 : carbohydrate antigen 72-4 AFP : alpha-fetoprotein CEA : carcinoembryonic antigen HE4 : human epididymal protein 4 HR : hazard ratio CI : confidence interval

Background: To determine the factors related to overall survival (OS) and progression-free survival (PFS) in endometrial carcinoma (EC) patients. Methods: A retrospective cohort study of 906 EC patients was conducted at Shengjing Hospital, China Medical University. Baseline information about the patients, tumor characteristics, and data on five serum biomarkers (CA125, CA19-9, CA72-4, CEA, and AFP) were collected. Groups and their survival rates were compared using log-rank tests and Kaplan-Meier analysis, respectively. Hazard ratios (HRs) and 95% confidence intervals (CIs) were determined using univariate or multivariate Cox proportional hazard models. The outcome measures used were OS, defined as the time between surgery and death or last follow-up for surviving patients, and PFS, defined as the time from the completion of initial surgery to either first progression, disease recurrence, or death. Results: Multivariate analysis showed lower PFS associated with age ≥ 66 years (P < 0.001), non-endometrioid histology (P = 0.015), low degree of tumor differentiation (P = 0.004), and FIGO stage III & IV (P = 0.002). Elevated CA125 (P = 0.042) and AFP (P = 0.016) were identified as independent biomarkers for PFS. Increased CA125 (P = 0.013), age ≥ 66 years (P < 0.001), non-endometrioid histology (P＜0.001), and FIGO stage III & IV (P = 0.015) were independent factors associated with OS. Analysis of the CA125 sub-group showed that individuals with elevated CA125 andAFP (P = 0.049) had significantly lower PFS. Conclusion: This study suggests that CA125 and AFP are prognostic biomarkers for EC

Endometrial cancer (EC) cells exhibit abnormal glucose metabolism, characterized by increased aerobic glycolysis and decreased oxidative phosphorylation. Targeting cellular glucose metabolism in these cells could be an effective therapeutic approach for EC. This study aimed to assess the roles of LIN28B, PCAT5, and IGF2BP3 in the glucose metabolism, proliferation, migration, and invasion of EC cells. LIN28B highly expressed in EC, binds and stabilizes PCAT5. PCAT5, overexpressed in EC, and its 1485-2288nt region can bind to the KH1-2 domain of IGF2BP3 to prevent MKRN2 from binding to the K294 ubiquitination site of IGF2BP3, thus stabilizing IGF2BP3. Finally, IGF2BP3 promotes the aerobic glycolysis, proliferation, migration and invasion of EC cells by stabilizing the key enzymes of glucose metabolism HK2 and PKM2. Taken together, our data reveal that the LIN28B/PCAT5/IGF2BP3 axis is critical for glucose reprogramming and malignant biological behavior in EC cells. Therefore, targeting this axis may contribute to the development of a novel therapeutic strategy for EC metabolism.

Endometrial cancer (EC) stem cells (ECSCs) are pivotal in the oncogenesis, metastasis, immune escape, chemoresistance, and recurrence of EC. However, the specific mechanism of stem cell maintenance in EC cells (ECCs) has not been clarified. We found that WTAP and m6A levels decreased in both EC and ECSCs, and that knocking down WTAP promoted ECCs and ECSCs properties, including proliferation, invasion, migration, cisplatin resistance, and self-renewal. The downregulation of WTAP leads to a decrease in the m6A modification of EGR1 mRNA, and it is difficult for IGF2BP3, as an m6A reader, to recognize and bind to EGR1 mRNA that has lost m6A modification, resulting in a decrease in the stability of EGR1 mRNA. A decrease in the EGR1 level led to a decrease of in the expression tumor suppressor gene PTEN, resulting in deregulation and loss of cellular homeostasis and thereby fostering EC stem cell traits. Notably, the enforced overexpression of WTAP, EGR1, and PTEN inhibited the oncogenic effects of ECCs and ECSCs in vivo, and the combined overexpression of WTAP + EGR1 and EGR1 + PTEN further diminished the tumorigenic potential of these cells. Our findings revealed that the WTAP/EGR1/PTEN pathway is important regulator of EC stem cell maintenance, chemotherapeutic resistance, and tumorigenesis, suggesting a novel and promising therapeutic avenue for treating EC.

Choriocarcinoma is a malignant cancer that belongs to gestational trophoblastic neoplasia (GTN). Herein, serum metabolomic analysis was performed on 29 GTN patients and 30 healthy individuals to characterize the metabolic variations during GTN progression. Ultimately 24 differential metabolites (DMs) were identified, of which, Equol was down-regulated in GTN patients, whose VIP score is the 3rd highest among the 24 DMs. As an intestinal metabolite of daidzein, the anticancer potential of Equol has been demonstrated in multiple cancers, but not choriocarcinoma. Hence, human choriocarcinoma cell lines JEG-3 and Bewo were used and JEG-3-derived subcutaneous xenograft models were developed to assess the effect of Equol on choriocarcinoma. The results suggested that Equol treatment effectively suppressed choriocarcinoma cell proliferation, induced cell apoptosis, and reduced tumorigenesis. Label-free quantitative proteomics showed that 136 proteins were significantly affected by Equol and 20 proteins were enriched in Gene Ontology terms linked to protein degradation. Tripartite motif containing 21 (TRIM21), a E3 ubiquitin ligase, was up-regulated by Equol. Equol-induced effects on choriocarcinoma cells could be reversed by TRIM21 inhibition. Annexin A2 (ANXA2) interacted with TRIM21 and its ubiquitination was modulated by TRIM21. We found that TRIM21 was responsible for proteasome-mediated degradation of ANXA2 induced by Equol, and the inhibitory effects of Equol on the malignant behaviors of choriocarcinoma cells were realized by TRIM21-mediated down-regulation of ANXA2. Moreover, β-catenin activation was inhibited by Equol, which also depended on TRIM21-mediated down-regulation of ANXA2. Taken together, Equol may be a novel candidate for the treatment for choriocarcinoma.

目的:探讨新冠肺炎疫情下妇产科住院医师规范化培训中线上授课的方式、方法和效果,以期在"停课不停学"下保障妇产科规范化培训的教学质量.方法:利用翻转课堂、雨课堂和腾讯会议技术手段完成住院医师规范化培训规范化培训的教学任务,同时进行随堂测试,课后对学生进行问卷调查,对教学效果进行评估.结果:规范化培训住院医师对线上教学认可度高,翻转课堂、雨课堂和腾讯会议联合的教学模式能够达到妇产科住院医师规范化培训的目的,同时提升学习主动性和学习兴趣,培养自主学习能力,提高临床思维能力和解决实际问题的能力,取得较为满意的教学效果.结论:翻转课堂、雨课堂和腾讯会议联合的教学模式比较受妇产科住院医师规范化培训学生的欢迎,在新冠肺炎疫情等突发事件形势下可进一步推广使用.

Tumor stem cells (TSCs) are thought to contribute to the progression and maintenance of cancer. Previous studies have suggested that plasmacytoma variant translocation 1 (PVT1) has a tumor-promoting effect on endometrial cancer; however, its mechanism of action in endometrial cancer stem cells (ECSCs) is unknown. Here, we found that PVT1 was highly expressed in endometrial cancers and ECSCs, correlated with poor patient prognosis, promoted the malignant behavior and the stemness of endometrial cancer cells (ECCs) and ECSCs. In contrast, miR-136, which was lowly expressed in endometrial cancer and ECSCs, had the opposite effect, and knockdown miR-136 inhibited the anticancer effects of down-regulated PVT1. PVT1 affected miR-136 specifically binding the 3’ UTR region of Sox2 by competitively “sponging” miR-136, thus positively saving Sox2. Sox2 promoted the malignant behavior and the stemness of ECCs and ECSCs, and overexpression Sox2 inhibited the anticancer effects of up-regulated miR-136. Sox2 can act as a transcription factor to positively regulate Up-frameshift protein 1 (UPF1) expression, thereby exerting a tumor-promoting effect on endometrial cancer. In nude mice, simultaneously downregulating PVT1 and upregulating miR-136 exerted the strongest antitumor effect. We demonstrate that the PVT1/miR-136/Sox2/UPF1 axis plays an important role in the progression and maintenance of endometrial cancer. The results suggest a novel target for endometrial cancer therapies.

N6 methyladenosine（m6A） is the most abundant internal modification of RNA in eukaryotic cells, which has attracted more and more attention in recent years. Many studies have found that m6A methylation can affect the occurrence and progression of tumors by regulating tumor-related biological functions. A lot of studies have reported that a variety of m6A regulatory factors are abnormally expressed in gynecological tumors, and that they play an important role in malignant gynecological tumors such as cervical cancer, ovarian cancer and endometrial cancer. In this review, we discuss the relationship between m6A regulatory factors and gynecological tumors, hoping to find potential diagnostic markers and therapeutic targets of gynecological tumors.

Ferroptosis is a newly proposed form of cell death in recent years, characterized by iron overload and accumulation of reactive oxygen species. There is increasing evidence that ferroptosis is associated with the occurrence and development of tumors.The tumor microenvironment is the environment required for the proliferation, differentiation and other activities of tumor cells.This article will review the concept and the mechanism of ferroptosis and its role in endometrial cancer, hoping to provide new ideas for the clinical treatment of endometrial cancer.

Background Some biomarkers collected from routine laboratory tests have shown important value in cancer prognosis. The study aimed to evaluate the prognostic significance of routine laboratory biomarkers in patients with endometrial cancer (EC) and to develop credible prognostic nomogram models for clinical application. Methods A total of 727 patients were randomly divided into a training set and a validation set. Cox proportional hazards models were used to evaluate each biomarker’s prognostic value, and independent prognostic factors were used to generate overall survival (OS) and progression-free survival (PFS) nomgrams. The efficacy of the nomograms were evaluated by Harrell’s concordance index (C-index), receiver operating characteristic (ROC) curves, decision curve analysis (DCA), calibration curves, X-tile analysis and Kaplan‒Meier curves. Results Ten significant biomarkers in multivariate Cox analysis were integrated to develop OS and PFS nomograms. The C-indices of the OS- nomogram in the training and validation sets were 0.885 (95% confidence interval (CI), 0.810–0.960) and 0.850 (95% CI, 0.761–0.939), respectively; those of the PFS- nomogram in the training and validation sets were 0.903 (95% CI, 0.866–0.940) and 0.825 (95% CI, 0.711–0.939), respectively. ROC, DCA and calibration curves showed better clinical application value for the nomograms incorporating routine laboratory biomarkers. X-tile analysis and Kaplan‒Meier curves showed that the nomograms were stable and credible in evaluating patients at different risks. Conclusions Nomogram models incorporating routine laboratory biomarkers, including NLR, MLR, fibrinogen, albumin and AB blood type, were demonstrated to be simple, reliable and favourable in predicting the outcomes of patients with EC.