Endometrial Cancer Metastasis Research Articles

Lymph node metastases in endometrial cancer: A modern assessment in the era of sentinel lymph node mapping and molecular classification

Lymph node metastases in endometrial cancer: A modern assessment in the era of sentinel lymph node mapping and molecular classification

Loss of vimentin expression in preoperative biopsies independently predicts poor prognosis, lymph node metastasis and recurrence in endometrial cancer

BackgroundPrecise preoperative risk classification of endometrial cancer is crucial for treatment decisions. Existing clinical markers often fail to accurately predict lymph node metastasis and recurrence risk. Loss of vimentin expression has emerged as a potential marker for predicting recurrence in low-risk endometrial cancer patients. We assessed whether vimentin expression in preoperative biopsies predicts poor prognosis and lymph node metastasis in a large multicentre cohort.MethodsVimentin expression was evaluated using immunohistochemistry in 1483 patients diagnosed with endometrial cancer across 14 hospitals in Europe. Expression levels of vimentin were analyzed in conjunction with clinical characteristics for predicting disease-specific survival and lymph node metastases.ResultsVimentin loss was significantly associated with aggressive disease and poor survival. Adjusted for clinicopathological variables, vimentin remained independently prognostic with a hazard ratio (HR) of 1.68 (95% CI 1.16–2.42, P = 0.006). Vimentin expression remained independently prognostic in endometrioid endometrial cancer- and FIGO staged 1 patient. Interestingly, vimentin loss independently predicted lymph node metastases, with an HR of 1.83 (95% CI 1.13–2.95, P = 0.014).ConclusionsLoss of vimentin in preoperative biopsies serves as an independent predictor of poor prognosis and lymph node metastases. Incorporating vimentin as a clinical marker can improve risk stratification and treatment decisions.

Assessing para-aortic nodal status in high-grade endometrial cancer patients with negative pelvic sentinel lymph node biopsy.

To determine the accuracy of pelvic sentinel lymph node biopsy (SLN) in detecting positive para-aortic (PA) lymph nodes in high-grade uterine cancer, and to determine the recurrence rate in patients with high-grade uterine cancers who did not receive adjuvant chemotherapy based on negative pelvic SLNs. This was a retrospective cohort study of patients with newly diagnosed, high-grade endometrial cancer who underwent surgery, including pelvic SLNs with or without PA node dissection, at a tertiary care institution between 2015 and 2020. Baseline demographics, surgical management, pathology data, and outcomes were analyzed using descriptive statistics, and survival analysis. Postoperative histology of the 110 patients meeting inclusion criteria was 45.5% grade 3 endometrioid, 36.4% serous, 10.9% clear cell, and 7.3% carcinosarcoma. On final pathology, 63.7% were stage 1, and 23.6% were stage 3C with positive nodes. A total of 63 patients (57.3%) had a PA lymph node dissection (56 bilateral, 7 unilateral) in addition to the pelvic SLN. Among this group, 5.8% (95% confidence interval 1.2%-16.0%) had a positive PA node despite a negative pelvic SLN. Among those with a negative pelvic SLN and no adjuvant chemotherapy (n = 75), the rate of distant recurrence was 14.7%, and 3-year recurrence-free survival was 71.9%. The rate of isolated PA node metastasis in high-grade endometrial cancers despite a negative pelvic SLN may be significantly higher than the accepted rate of isolated PA node metastasis in low-grade endometrial cancer. This supports adjuvant treatment decisions continuing to incorporate primary tumor pathology and molecular classification.

6634 Dual-Mediated PTH And Osteolytic Hypercalcemia In Metastatic Endometrial Carcinoma

Abstract Disclosure: C.K. Persaud: None. D.J. Beckman: None. Background: Hypercalcemia of malignancy occurs in 20-30% of advanced stage cancer patients. Etiologies include parathyroid hormone-related peptides (PTHrP)-mediated, osteolytic metastases-mediated, overproduction of 1,25-dihydroxycholecalciferol, and rarely parathyroid hormone (PTH)-mediated. PTH-mediated hypercalcemia of malignancy is rare and occurs through ectopic PTH production or primary hyperparathyroidism. We report a rare case of both PTH-mediated and osteolytic-mediated hypercalcemia in the setting of malignancy. Clinical Case: A 57-year-old female with history of endometrial cancer and multiple solid organ metastasis, presented with two weeks of progressive poor oral intake, nausea, emesis, and right flank pain. On hospital admission, she had a serum calcium of >20.1 mg/dL (8.6-10.2), PTH of 203 pg/mL (15.0-65.0), and creatinine of 1.7 mg/dL (0.7-1.2, baseline 1.3). Non-contrasted CT chest/abdomen/pelvis noted increased size of known right adrenal metastasis, new left adrenal metastasis, periaortic lymphadenopathy, and scattered nodules in the subcutaneous tissues of the abdomen and chest, however bone metastasis were not noted. Patient’s hypercalcemia was treated with zoledronic acid, calcitonin, cinacalcet, and eventually denosumab due to difficulty controlling hypercalcemia. Additional labs obtained during evaluation included ionized calcium >2.5 nmol/L (1.12-1.32), PTHrP <2.0 pmol/L (<2.0), 1,25-dihydroxycholecalciferol <10 pg/mL (21-65). Patient’s right adrenal metastasis biopsy one month prior to admission was subsequently stained for PTH and was negative. Technetium-99m sestamibi scan was obtained for localization of parathyroid adenoma or carcinoma. The scan did not localize, however did show numerous new lytic lesions in the skull, spine, sternum, rib cage, and right humerus. Patient’s hospital course was complicated by progressively worsening renal function, anemia, and thrombocytopenia. Patient was discharged to a long-term acute rehab facility off hypercalcemia treatment with a corrected calcium of 10.0 mg/dL. Conclusion: PTH-mediated hypercalcemia is a rare cause of hypercalcemia of malignancy. PTH levels are typically low or low-normal in osteolytic mediated hypercalcemia. Generally, if PTH is elevated in hypercalcemia, an alternate etiology is not evaluated. This case highlights a rare dual-mediated hypercalcemia of malignancy. The patient’s PTH level elevation was discordant with her high degree of hypercalcemia and prolonged treatment course. She was subsequently found to have widespread bone metastases contributing to hypercalcemia. While multiple etiologies of hypercalcemia can be rare, it is important to evaluate for all contributing causes, especially with additional clinical conditions, such as malignancy. Presentation: 6/3/2024

Sentinel node mapping decreases the risk of failed detection of isolated positive para-aortic lymph node in endometrial cancer

BackgroundIsolated positive para-aortic lymph node metastasis in endometrial cancer is an uncommon event, ranging from 1% to 3%.ObjectiveOur aim was to evaluate the impact of sentinel lymph node (SLN) mapping...

KIFC1 depends on TRIM37-mediated ubiquitination of PLK4 to promote centrosome amplification in endometrial cancer

Endometrial cancer (EC), as one of the most common cancers, severely threatens female reproductive health. Our previous study has shown that Kinesin family member C1 (KIFC1) played crucial roles in the progression of EC. In addition, abnormal centrosome amplification, which was reported to be partially regulated by KIFC1, usually occurred in different cancers. However, whether KIFC1 promoted EC through centrosome amplification and the potential mechanism remain to be revealed. The present study demonstrated that overexpressed KIFC1, which exhibited a worse prognosis, had a positive correlation with an increased number of centrosomes in human EC samples. In addition, KIFC1 overexpression in EC cells prompted centrosome amplification, chromosomal instability, and cell cycle progression. Moreover, we demonstrated that KIFC1 inhibited E3 ubiquitin-protein ligase TRIM37 to maintain the stability of PLK4 by reducing its ubiquitination degradation, and finally promoting centrosome amplification and EC progression in vitro. Finally, the contributing role of KIFC1 and the inhibitory effect of TRIM37 on EC development and metastasis was verified in a nude mouse xenograft model. Our study elucidated that KIFC1 depends on TRIM37-mediated reduced ubiquitination degradation of PLK4 to promote centrosome amplification and EC progression, thus providing a potential prognostic marker and promising therapeutic target for EC in the future.

The oncogenic role of EIF4A3/CDC20 axis in the endometrial cancer.

Eukaryotic initiation factor 4A-3 (EIF4A3) is a key component of the exon junction complex (EJC) and is extensively involved in RNA splicing, inducing mRNA decay, and regulating the cell cycle and apoptosis. However, the potential role of EIF4A3 in EC has not been comprehensively investigated and remains unknown. Here, we report that the expression level of EIF4A3 is dramatically elevated in endometrial cancer (EC) samples compared with normal EC samples via bioinformatics analysis and immunohistochemistry analysis, and that high expression of EIF4A3 promotes the proliferation, migration, and invasion of EC cells. Mechanistically, we found that high EIF4A3 expression stabilized cell division cyclin 20 (CDC20) mRNA, and high EIF4A3 expression induced pro-carcinogenic effects in EC cells that were efficiently antagonized upon knockdown of CDC20, as well as Apcin, an inhibitor of CDC20. These findings reveal a novel mechanism by which high expression of EIF4A3 induces CDC20 upregulation, thus leading to EC tumorigenesis and metastasis, indicating a potential treatment strategy for EC patients with high EIF4A3 expression using Apcin. KEY MESSAGES: The expression level of EIF4A3 was dramatically elevated in endometrial cancer (EC) samples compared with normal endometrial cancer samples. High EIF4A3 expression stabilized CDC20 mRNA, and high EIF4A3 expression induced pro-carcinogenic effect in EC cells which was efficiently antagonized upon knockdown of CDC20. Apcin, an inhibitor of CDC20, could effectively counteract high expression of EIF4A3 inducing EC tumourigenesis and metastasis, indicating the potential treatment strategy for EC patients with EIF4A3 high expression by using Apcin.

MYO3B promotes cancer progression in endometrial cancer by mediating the calcium ion-RhoA/ROCK1 signaling pathway

PurposeThis study aimed to investigate the effect of MYO3B on endometrial cancer (EC) proliferation and invasion.MethodsThe expression of MYO3B in EC tissues and cells was analyzed using TCGA database, immunohistochemical staining, real-time PCR, and western blot (WB). Cell proliferation was detected by CCK8, Annexin V-APC/PI flow cytometry was used to detect apoptosis, intracellular calcium ion (Ca2+) was detected by flow cytometry with Fluo-4 AM fluorescent probe, cell migration by scratch assay, and cell invasion by Transwell assay, and the expression of proteins related to Ca2+ homeostasis and RhoA/ROCK1 signaling pathway was detected by WB and immunofluorescence staining.ResultsThe expression of MYO3B was an influential factor in EC recurrence, and the expression of MYO3B was significantly up-regulated in EC tissues and cells, but down-regulated in KLE cells, and MYO3B knockdown inhibited the proliferation, migration, and invasion ability of EC cells and promoted apoptosis, suggesting that MYO3B plays a tumor-promoting role in EC. Furthermore, MYO3B knockdown decreased Ca2+ concentration in EC cells and the RhoA/ROCK1 signaling pathway was inhibited, and the effect of MYO3B knockdown on RhoA/ROCK1 signaling was reversed by treatment with the Calmodulin agonist CALP-2, and the effects of MYO3B knockdown on cell proliferation, migration, and invasion were reversed after treatment with the RhoA agonist U-46,619.ConclusionMYO3B promotes the proliferation and migration of endometrial cancer cells via Ca2+-RhoA/ROCK1 signaling pathway. High expression of MYO3B may be a biomarker for EC metastasis.

Endometrial cancer risk stratification using MRI radiomics: corroborating with choline metabolism

Background and purposeRadiomics offers little explainability. This study aims to develop a radiomics model (Rad-Score) using diffusion-weighted imaging (DWI) to predict high-risk patients for nodal metastasis or recurrence in endometrial cancer (EC) and corroborate with choline metabolism.Materials and methodsFrom August 2015 to July 2018, 356 EC patients were enrolled. Rad-Score was developed using LASSO regression in a training cohort (n = 287) and validated in an independent test cohort (n = 69). MR spectroscopy (MRS) was also used in 230 patients. Nuclear MRS measured choline metabolites in 70 tissue samples. The performance was compared against European Society for Medical Oncology (ESMO) risk groups. A P < .05 denoted statistical significance.ResultsRad-Score achieved 71.1% accuracy in the training and 71.0% in the testing cohorts. Incorporating clinical parameters of age, tumor type, size, and grade, Rad-Signature reached accuracies of 73.2% in training and 75.4% in testing cohorts, closely matching the performance to the post-operatively based ESMO's 70.7% and 78.3%. Rad-Score was significantly associated with increased total choline levels on MRS (P = .034) and tissue levels (P = .019).ConclusionsDevelopment of a preoperative radiomics risk score, comparable to ESMO clinical standard and associated with altered choline metabolism, shows translational relevance for radiomics in high-risk EC patients.Trial registrationThis study was registered in ClinicalTrials.gov on 2015–08-01 with Identifier NCT02528864.

WTAP/IGF2BP3 mediated m6A modification of the EGR1/PTEN axis regulates the malignant phenotypes of endometrial cancer stem cells

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.

Cluster analysis of social isolation in gynecologic cancer patients: A cross-sectional survey.

To identify the distinct clusters of social isolation among gynecologic cancer patients and analyze the predictive factors associated with each cluster. A total of 463 patients diagnosed with gynecologic cancer were recruited from three tertiary hospitals between November 2021 and March 2023. Using a two-step cluster analysis, participants were categorized into clusters based on social isolation scales. Multinomial logistic regression was then employed to predict factors influencing the identified clusters. Social isolation in gynecologic cancer patients manifested in four distinct clusters: mild social isolation subgroup (13.8%), moderate social isolation subgroup (32.0%), severe isolation subgroup (33.5%), and high social isolation (20.70%). Multivariate logistic regression analysis revealed that cognitive emotional regulation, social support, negative emotions, endometrial cancer, and disease recurrence or metastasis were significant predictive factors for the identified social isolation clusters (P < 0.05). The study underscored the heterogeneity in the social isolation characteristics of gynecologic cancer patients. Consequently, healthcare professionals should prioritize the identification of potential high-risk groups and devise personalized interventions to prevent and mitigate the occurrence of social isolation.

Enhancing prognostic insights: myometrial invasion patterns in endometrial carcinoma, with emphasis on MELF pattern-a comprehensive review and meta-analysis.

The microcystic, elongated, and fragmented (MELF) pattern, characterized by myxoid and inflamed stroma, is readily identifiable as a form of myometrial infiltration. This meta-analysis endeavors to assess the prognostic significance of MELF infiltration patterns in patients diagnosed with endometrial cancer. A comprehensive literature search, spanning until 11 October 2023, across PubMed, Embase, Cochrane, and Web of Science databases, identified 23 relevant studies involving 5199 patients. Data analysis was performed using Stata 16.0. Analysis indicates that MELF infiltration predicts a higher risk of lymph node metastasis in endometrial cancer patients [hazard ratios (HR) = 5.05; 95% confidence interval (CI), 3.62-7.05; P < 0.05]. Notably, this association remains consistent across various patient demographics, analytical approaches, study designs, and treatment modalities. However, MELF infiltration does not significantly correlate with recurrence (HR = 1.05; 95% CI, 0.73-1.52; P > 0.05), overall survival (HR = 1.24; 95% CI, 0.91-1.68; P > 0.05), or disease-free survival (HR = 1.40; 95% CI, 0.85-2.28; P > 0.05). While MELF infiltration heightens the risk of lymph node metastasis in endometrial cancer, its impact on recurrence, overall survival, and disease-free survival remains statistically insignificant.

15P Loss of vimentin expression in preoperative biopsies independently predicts lymph node metastasis in endometrial cancer

15P Loss of vimentin expression in preoperative biopsies independently predicts lymph node metastasis in endometrial cancer

Skin metastases of endometrial cancer

About 400 thousand of new cases of endometrial cancer is registered in the world every year. Previously uncommon (for this type of malignancy) metastatic sites, such as brain or skin, have been observed over the past 15 years. Skin metastases of endometrial cancer are extremely rare and occur in less than 1 % of cases. We present a clinical case of atypical metastasis of endometrial cancer to the skin of the pubic region in a patient who underwent combined treatment.

Abstract 4126: The inhibitory effect of statins on distant metastasis and recurrence of endometrial cancer

Abstract Endometrial cancer (EC) is the most common gynecologic malignancy. The most common histological type is endometrioid endometrial cancer (EEC). While the majority of patients present with early-stage and low-grade EEC and have an excellent prognosis, a subset develops distant recurrence derived from EEC after initial treatment of the primary. However, the exact mechanism of distant metastasis and recurrence from EEC is still unclear. In addition, the lack of suitable pre-clinical models is a significant barrier to research for distant metastasis and recurrent cancer derived from EEC. Our preclinical EEC model, the ablation of both Mig-6 and Pten in the uterus (Pgrcre/+Mig-6f/fPtenf/f; Mig-6d/dPtend/d), dramatically accelerates the development of EEC compared to single ablation of either gene. The ablation of both Mig-6 and Pten in the uterus (Pgrcre/+Mig-6f/f Ptenf/f; Mig-6d/dPtend/d mice) displayed distant metastases into the ovary, diaphragmatic skeletal muscle, lymph node, and lung. However, the Ptend/d mice exhibited endometrial cancer without distant metastases. After hysterectomy of EEC confined to uterus, Mig-6d/dPtend/d mice exhibited recurrent EEC in abdomen and lung. To identify prognostic factors for distant metastatic and recurrent EEC, we performed transcriptomic analysis in endometrial hyperplasia, a precancerous condition, from Ptend/d and Mig-6d/dPtend/d mice. Our transcriptomic analysis identified that cholesterol biosynthesis was the most significantly activated pathway in Mig-6d/dPtend/d mice compared to Ptend/d mice. Statins, also known as HMG-CoA reductase inhibitors, are the most common cholesterol-lowering drugs. We evaluated the effect of atorvastatin on tumorigenesis and recurrence of EEC. Mig-6d/dPtend/d mice treated with atorvastatin displayed significant reduction of tumor size compared to vehicle treated group. For vehicle-treated group, our pathological analysis revealed EEC outside the uterus, therefore EEC had disseminated to involve the ovary, diaphragmatic skeletal muscle, lymph node, and lung. However, EEC was confined to the uterus in the atorvastatin treated group. Furthermore, atorvastatin treatment reduced the rate of recurrent EEC development. This data demonstrated that atorvastatin has a remarkable inhibitory effect on metastasis and recurrence of EEC in Mig-6d/d Ptend/d mice. Our results suggest that statins suppress development of distant metastasis and recurrence in mouse models of EEC with Pten and Mig-6 deficiency by inhibiting cholesterol biosynthesis. Citation Format: Keun Cheon Kim, Jung Yoon Yoo, Russell R Broaddus, Eunhee M Jeong, Mark I Hunter, Tae Hoon Kim, Jae-Wook Jeong. The inhibitory effect of statins on distant metastasis and recurrence of endometrial cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4126.

Risk factors for pelvic and para-aortic lymph node metastasis in non-endometrioid endometrial cancer

PurposeThe aim of this study was to evaluate the risk factors for pelvic lymph node metastasis (LNM) and para-aortic LNM in non-endometrioid endometrial cancer (non-EEC). MethodsA total of 283 patients with non-EEC hospitalized in the First Affiliated Hospital of Zhengzhou University from January 2012 to December 2020 were included. Various characteristics were retrospectively analyzed in relation to LNM. ResultsUnivariable and multivariable logistic regression analysis revealed cervical stromal invasion (OR = 3.441, 95% CI = 1.558–7.6, p = 0.002), myometrial invasion ≥1/2 (OR = 2.661, 95% CI = 1.327–5.337, p < 0.006), lymphovascular space involvement (LVSI) (OR = 4.118, 95% CI = 1.919–8.837, p < 0.001), positive peritoneal cytology (OR = 2.962, 95% CI = 1.344–6.530, p = 0.007), CA125 (OR = 1.002, 95% CI = 1–1.004, p = 0.026) were the independent risk factors for pelvic LNM. And myometrial invasion ≥1/2 (OR = 5.881, 95% CI = 2.056–16.427, p = 0.001), LVSI (OR = 4.962, 95% CI = 1.933–12.740, p = 0.001), adnexal (OR = 5.921, 95% CI = 2.003–17.502, p = 0.001) were the independent risk factors for para-aortic LNM. With the increase of independent risk factors, the rates of LNM were increased significantly. ConclusionsCervical stromal invasion, myometrial invasion ≥1/2, LVSI, positive peritoneal cytology, and CA125 were risk factors for pelvic LNM. Myometrial invasion ≥1/2, LVSI and involvement of the adnexa were risk factors for para-aortic LNM which could provide a good basis to help predict which non-EEC patients are at higher risk for LNM.

The Predictive Value of Preoperative Inflammatory Markers / Lymphocyte Ratios for Endometrial Cancer; What does the eosinophil to lymphocyte ratio means for survival?

Aim: &#x0D; In various solid tumors, cancer-associated inflammation is associated with adverse long-term outcomes. The purpose of this study was to examine the influence of the preoperative neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and other systemic inflammatory markers on lymph node metastasis and 5-year survival in endometrial cancer.&#x0D; Materials and Method: &#x0D; A total of 379 female patients at the Gynecology and Obstetrics Clinic of the University Hospital with a final postoperative pathology of endometrial cancer were included in the 5-year survival study. The preoperative total neutrophil, monocyte, eosinophil, and platelet counts were divided by the lymphocyte count to obtain the NLR, monocyte-to-lymphocyte ratio (MLR), eosinophil-to-lymphocyte ratio (ELR), and PLR values. All patients underwent bilateral pelvic paraaortic lymph node dissection and omentectomy in addition to total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH + BSO). The pathology lab at our university evaluated all cytology and postoperative specimens. The staging system used was the FIGO 2009 surgical staging system.&#x0D; Results: &#x0D; The results of our study showed significant correlations between lymph node metastasis and NLR, eosinophil-to-lymphocyte ratio (ELR), and PLR. Only a significant correlation between ELR and survival was discovered when the relationship with 5-year survival was examined. Aditionally significant correlations existed between NLR and cervical stromal involvement, cytology positivity, and stage.&#x0D; Conclusion: &#x0D; The prognostic factors for lymph node metastasis are NLR, PLR, and ELR. Only ELR is predictive of 5-year survival, but more prospective studies on ELR survival prediction are needed.

Preoperative evaluation and a nomogram prediction model for pelvic lymph node metastasis in endometrial cancer

ObjectiveThe primary objective of this study is to explore the preoperative risk factors of pelvic lymph node metastasis (PLNM) in endometrial cancer patients, and construct a nomogram prediction model. Materials and methodsWe retrospectively collected various preoperative clinical characteristics of patients and analyzed their relationship with PLNM. Logistic regression analysis was used to screen for independent risk factors for PLNM of endometrial cancer. A nomogram prediction model was constructed, the receiver operating characteristic (ROC), calibration curve and decision curve analysis (DCA) were constructed and used to assess discrimination, calibration, and net benefit. ResultsOut of the 276 patients, 74 (26.81%) with postoperative pathological confirmation of PLNM. Multivariate logistic regressive analysis demonstrated that preoperative depth of myometrial invasion (DIM) ≥50% determined by Magnetic Resonance Imaging (MRI) (p = 0.003), carbohydrate antigen 125 (CA125) (p = 0.030), carbohydrate antigen 19–9 (CA 19–9) (p = 0.044), and platelet/lymphocyte ratio (PLR) (p = 0.025) could serve as independent risk factors for PLNM. A risk factors-based nomogram prediction model was constructed, which showed good discrimination (AUC = 0.841, p < 0.001) and good efficacy (C-index = 0.842) and good calibration (mean absolute error = 0.046). DCA showed that the model can provide clinical benefits. ConclusionsPreoperative DIM ≥50% determined by MRI, serum CA 19–9, CA125 and PLR could be utilized to predict PLNM in endometrial cancer patients. This nomogram prediction model can provide preoperative help for evaluation and identification of patients with endometrial cancer, and provide a theoretical basis for clinical intervention.

ACSL1-Mediated Fatty Acid β-Oxidation Enhances Metastasis and Proliferation in Endometrial Cancer.

Gynecological malignancies, such as endometrial cancer (EC) and uterine cancer are prevalent. Increased Acyl-CoA synthetase long-chain family member 1 (ACSL1) activity may contribute to aberrant lipid metabolism, which is a potential factor that contributes to the pathogenesis of endometrial cancer. This study aimed to elucidate the potential molecular mechanisms by which ACSL1 is involved in lipid metabolism in endometrial cancer, providing valuable insights for targeted therapeutic strategies. Xenograft mouse models were used to assess the effect of ACSL1 on the regulation of endometrial cancer progression. ACSL1 protein levels were assessed via immunohistochemistry and immunoblotting analysis. To assess the migratory potential of Ishikawa cells, wound-healing and Transwell invasion assays were performed. Changes in lipids in serum samples from mice with endometrial cancer xenotransplants were examined in an untargeted lipidomic study that combined multivariate statistical methods with liquid chromatography‒mass spectrometry (LC/MS). Patient sample and tissue microarray data suggested that higher ACSL1 expression is strongly associated with the malignant progression of EC. Overexpression of ACSL1 enhances fatty acid β-oxidation and 5'-adenylate triphosphate (ATP) generation in EC cells, promoting cell proliferation and migration. Lipidomic analysis revealed that significant changes were induced by ACSL1, including changes to 28 subclasses of lipids and a total of 24,332 distinct lipids that were detected in both positive and negative ion modes. Moreover, pathway analysis revealed the predominant association of these lipid modifications with the AMPK/CPT1C/ATP pathway and fatty acid β-oxidation. This study indicates that ACSL1 regulates the AMPK/CPT1C/ATP pathway, which induces fatty acid β-oxidation, promotes proliferation and migration, and then leads to the malignant progression of EC.

FKBP38 suppresses endometrial cancer cell proliferation and metastasis by inhibiting the mTOR pathway

Endometrial cancer (EC) is a common gynecological malignancy, and advanced-stage or recurrent EC is associated with a high mortality rate owing to the ineffectiveness of currently available treatments. FK506-binding protein 38 (FKBP38) is a member of the immunophilin family and inhibits melanoma and breast cancer cell metastasis. However, the functions of FKBP38 and its potential mechanism in EC remain unclear. Herein, we analyzed the expression levels of FKBP38 in EC cells and found that the FKBP38 expression was high in Ishikawa cells, and low in AN3CA cells, traditionally considered a low grade and a high grade cell line, respectively, in pathology classification. Moreover, FKBP38 inhibited cell proliferation, migration and invasion in EC cells, FKBP38 knockdown significantly promoted tumor growth of Ishikawa cells in a subcutaneous xenograft model and increased the number of lung metastases of Hec-1-A cells in a metastatic mouse model. Furthermore, FKBP38 suppressed several target proteins of epithelial-to-mesenchymal transition (EMT) and reduced the phosphorylation of ribosomal S6 protein (S6), eukaryotic initiation factor 4E-binding protein 1 (4EBP-1), indicating the potent inhibition of the mammalian target of rapamycin (mTOR) pathway. Meanwhile, the inhibition of mTOR neutralized the elevation of EC cell proliferation, migration and invasion after FKBP38 knockdown. In summary, FKBP38 would exert a tumor-suppressing role by modulating the mTOR pathway. Our results indicate that FKBP38 may be considered as a factor of EC metastasis and a new target for EC therapeutic intervention.