BACKGROUND/OBJECTIVES:Uterine serous carcinoma (USC) is an aggressive subtype of endometrial cancer characterized by high recurrence rates and poor response to conventional therapies, resulting in unfavorable clinical outcomes. Eicosapentaenoic acid (EPA), an omega-3 polyunsaturated fatty acid, has demonstrated anti-cancer activity in multiple malignancies. METHODS:This study used two USC cell lines, ARK1 and SPEC2, to evaluate the effects of EPA on cell proliferation, invasion, cell cycle profile, stress response, and apoptosis. The potential synergistic effects of EPA combined with carboplatin were also examined. Western blotting was used to examine EPA's effects on downstream pathways related to cellular stress, inflammation, and epithelial-mesenchymal transition (EMT). RESULTS:EPA treatment markedly reduced cell proliferation and colony formation, with IC50 values of 28.96 µM for ARK-1 cells and 14.96 µM for SPEC-2 cells compared with control groups. It also induced G1 phase cell cycle arrest, increased cellular stress, triggered caspase-dependent apoptotic cell death, and suppressed invasive capacity. Moreover, EPA effectively counteracted TNF-α-stimulated upregulation of COX-2 and phosphorylated NF-κB. The combined treatment with EPA and carboplatin resulted in synergistic inhibition of cell viability and migration. Western blotting analysis showed that EPA attenuates the NF-κB and AKT/mTOR signaling pathways, promotes the expression of cellular stress-related proteins, and inhibits the expression of EMT-related proteins in both cell lines. CONCLUSIONS:EPA exhibits potent anti-tumor activity against USC cells and enhances the efficacy of carboplatin. These data indicate that EPA has potential as a low-toxicity, multi-target adjuvant treatment for USC, necessitating additional pre-clinical and clinical investigation.

Endometrial cancer (EC) is the most common gynecological malignancy, frequently characterized by PTEN deletion, activation of the AKT/mTOR pathway, and limited effective treatment options for recurrent and advanced patients. High-dose ascorbate or combined with other chemotherapeutic agents shows potent antitumor effects in vitro and in vivo. In this study, high-dose ascorbate significantly inhibited cell proliferation and invasion, increased cellular stress and DNA damage, and induced cell cycle arrest and apoptosis in EC cells. Oral or intraperitoneal injections of high-dose ascorbate for 4 weeks effectively inhibited tumor growth in LKB1fl/flp53fl/fl -mouse model of EC, with intraperitoneal injections being more effective than oral administration. N-acetylcysteine partially reversed the antitumor effects of ascorbate in EC cells and tumor growth in LKB1fl/flp53fl/fl -mice. PTEN knockdown by shRNA reduced the antitumor sensitivity of EC cells to ascorbate, while inhibition of the AKT/mTOR pathway by Ipatasertib significantly enhanced the antitumor activity of ascorbate in EC cells. Ascorbate combined with paclitaxel synergistically inhibited tumor growth compared to either agent alone in LKB1fl/flp53fl/fl -mice. Overall, high-dose ascorbate exhibits antitumor activity partially through PTEN/AKT/mTOR and cell stress pathways, and these antitumor effects were heightened when combined with paclitaxel in EC. Clinical trials of ascorbate combined with paclitaxel deserve further investigation in EC patients.

Polo-like kinase 1 (Plk1) is widely recognized as an oncogene that promotes cell proliferation by regulating cell division, DNA damage response, and genome stability and has been shown to be overexpressed in many cancers, including endometrial cancer. Targeting Plk1 by onvansertib has been shown to have anti-tumor activity in pre-clinical models of multiple cancers and is currently being evaluated in phase 1 and 2 clinical trials in cancer patients. In this study, we evaluated the potential anti-tumorigenic effects of onvansertib in endometrial cancer cells and the LKB1fl/fl p53fl/fl mouse model of endometrial cancer. Onvansertib inhibited cellular proliferation, caused G2 phase arrest, induced cellular stress and apoptosis, and inhibited cellular migration and invasion in endometrial cancer cells. Combined treatment with onvansertib and paclitaxel led to synergistic inhibition of cell proliferation. Onvansertib treatment for 4 weeks significantly reduced tumor growth in LKB1fl/flp53fl/fl mice. Given these promising pre-clinical results, further studies are needed to evaluate the clinical translatability of onvansertib combined with paclitaxel as an effective treatment for endometrial cancer.

Ovarian cancer, particularly epithelial ovarian cancer (EOC), is the most aggressive and lethal gynecologic malignancy, necessitating the development of innovative and potent therapies to improve its prognosis. Human polo-like kinase 1 (PLK1), a key regulator of cell division, is crucial for driving mitosis and cytokinesis and maintaining genomic stability through phosphorylation of a few different substrates. PLK1 is found to be overexpressed in EOC tissues compared with normal ovarian tissues and is strongly associated with the prognosis of patients with stage I and II EOC. Targeting PLK1 markedly inhibits cell proliferation, causes cell cycle G2 phase arrest and DNA damage, induces apoptosis, and reduces tumor growth in preclinical models of EOC. In addition, the combination of PLK1 inhibitors with chemotherapeutic agents such as paclitaxel, cisplatin, doxorubicin, and PARP inhibitors exhibits effective synergistic effects in cell proliferation and tumor growth in EOC. Phase I and II clinical trials of PLK1 inhibitors in patients with EOC have shown favorable safety but inconsistent clinical efficacy. This review analyzes the existing preclinical and clinical data on PLK1 and evaluates the antitumor effects of PLK1 in EOC, offering perspectives on the potential application of PLK1 in the treatment of EOC.

Chronic inflammation is a key contributor to carcinogenesis, progression, and chemoresistance in ovarian cancer, making inflammatory pathways a logical therapeutic target for the treatment of this disease. Sulindac, a commonly used non-steroidal anti-inflammatory drug, has demonstrated anti-proliferative and anti-invasive effects on several preclinical models of cancer. In this study, we investigated the antitumorigenic effects of sulindac in human ovarian cancer cell lines and a transgenic mouse model of ovarian cancer (KpB). MTT and colony formation assays were used to evaluate cell proliferation. Cell cycle was detected by Cellometer. ELISA assays were conducted to evaluate the changes of cellular stress, apoptosis and adhesion, while invasion was determined by wound healing assay. Protein expression was examined through Western blotting and immunohistochemistry. Our results demonstrated that sulindac significantly inhibited cell proliferation, induced cellular stress and apoptosis, caused G1 phase cell cycle arrest, and reduced cell invasion, and suppressed Cox-2 and NF-κB pathways in the MES and OVCAR5 cell lines. Inhibition of cellular stress by N-acetylcysteine partially reversed the anti-proliferative and anti-invasive effects of sulindac. The combination of sulindac and paclitaxel produced synergistic effects in inhibiting cell growth in both paclitaxel sensitive and resistant MES cells. Treatment with sulindac for 4 weeks effectively reduced tumor growth, improved serum levels of inflammatory cytokines and chemokines, and reduced the expression of Cox-2 of ovarian tumors in KpB mice compared with untreated mice. These findings provide support for the development of clinical trials repurposing sulindac in the treatment of OC, possibly in combination with paclitaxel.

Uterine serous carcinoma (USC) belongs to the non-endometrioid subtype of endometrial cancer that is known for its highly aggressive behavior and poor prognosis, highlighting the warrant of novel strategies for the treatment of USC. PLK1 is a type of serine/threonine kinase that is crucial for controlling the progression of the cell cycle, DNA damage response, and genome stability. Targeting PLK1 exhibits potent anti-tumorigenic activity in pre-clinical models of multiple cancer types, and several PLK1 inhibitors have shown significant clinical benefit and favorable safety profiles alone or in combination with other chemotherapeutic agents. Onvansertib is an oral, selective PLK1 inhibitor that exhibits anti-proliferative activity in multiple types of cancer cell and animal models and has demonstrated clinical activity and a favorable safety profile in recent clinical trials. Hence, we investigated the anti-tumorigenic effects of onvansertib in USC cell lines. Nanomolar concentrations of onvansertib significantly inhibited cellular proliferation, led to cell cycle G2 arrest, induced cellular stress and apoptosis, caused DNA damage, and reduced cell adhesion and invasion in ARK-1 and SPEC-2 cells. The combination of onvansertib with paclitaxel demonstrated a synergistic effect in cell proliferation inhibition via inducing cell apoptosis and DNA damage. Our results provide preclinical evidence that onvansertib may be an effective strategy to treat USC and deserves further evaluation in animal models and clinical trials.

Ascorbate (vitamin C) is an essential vitamin for the human body and participates in various physiological processes as an important coenzyme and antioxidant. Furthermore, the role of ascorbate in the prevention and treatment of cancer including gynecological cancer has gained much more interest recently. The bioavailability and certain biological functions of ascorbate are distinct in males versus females due to differences in lean body mass, sex hormones, and lifestyle factors. Despite epidemiological evidence that ascorbate-rich foods and ascorbate plasma concentrations are inversely related to cancer risk, ascorbate has not demonstrated a significant protective effect in patients with gynecological cancers. Adequate ascorbate intake may have the potential to reduce the risk of human papillomavirus (HPV) infection and high-risk HPV persistence status. High-dose ascorbate exerts antitumor activity and synergizes with chemotherapeutic agents in preclinical cancer models of gynecological cancer. In this review, we provide evidence for the biological activity of ascorbate in females and discuss the potential role of ascorbate in the prevention and treatment of ovarian, endometrial, and cervical cancers.

Background Cervical cancer is a highly aggressive cancer that seriously affects the physical and mental health and quality of life of women, especially for women in developing countries. Therefore, cervical cancer has always been the focus of research, and in recent years, various studies on cervical cancer have emerged one after another. Methods Our study aimed to illustrate the development trends in cervical cancer research in China from 2013 to 2022 and compare the findings with studies in other parts of the world during the same period by using bibliometric analysis and the Science Citation Index Expanded. Literature data were analyzed and visualized by using CiteSpace and VOSviewer. Results The results show that the number of articles on cervical cancer has increased in recent years, among which articles on the pathogenesis and epidemiological characteristics of cervical cancer account for the majority. The research in China has developed rapidly in recent years, but there is still a certain gap compared with other developed countries. Conclusion Bibliometric and visualization analyses offer a unique and objective perspective in the field of cervical cancer and may assist scholars in identifying new research directions.

Abstract Objectives: Given the intricate relationship between inflammation and ovarian cancer (OC) development and progression, anti-inflammatory drugs may have potential in the prevention and treatment of OC. Sulindac exhibits potent anti-inflammatory effects through inhibition of COX1/COX2 pathways and promising anti-tumor activity in pre-clinical models of colorectal and endometrial cancer. Thus, we investigated the efficacy of sulindac as an anti-tumorigenic agent in OC pre-clinical cell and mouse models. Methods: The human OC cell lines, MES and OVCAR5, and the K18-gT121+/-;p53fl/fl;Brca1fl/fl (KpB) mouse model of high-grade serous OC were used. Cellular proliferation was assessed by MTT and colony count assays. Apoptosis was assessed using cleaved caspase 3, 8, and 9 assays. To measure cellular stress, production of reactive oxygen species was measured by DCFH-DA assay, and the JC1 assay was used to assess changes in mitochondrial membrane potential. Cellular adhesion was evaluated by laminin assay, and cellular migration was determined by wound healing assay. Western immunoblotting was used to assess the effects of sulindac on downstream targets related to cellular stress, apoptosis, cellular invasion potential, cell cycle control, and inflammation. The KpB mice were treated with sulindac (7.5 mg/kg, oral gavage, daily) or placebo for four weeks. Results: Sulindac inhibited cellular proliferation in a dose-dependent manner in the MES and OVCAR5 cells, with IC50s of 75.3 and 75.69 μM, respectively. Sulindac (100 μM) reduced colony formation by 81% in the MES cells and by 49% in the OVCAR5 cells (p<0.01). Treatment of MES and OVCAR5 cells with sulindac increased ROS production and decreased mitochondrial membrane potential, in a dose-dependent manner (p<0.01). Sulindac induced activity of cleaved caspase 3, 8, and 9, in MES and OVCAR5 cells (p<0.01). In addition, sulindac (100 μM) effectively decreased cellular adhesion by 31% in MES cells and by 23% in OVCAR5 cells (p<0.01). These results were confirmed by Western immunoblotting demonstrating that sulindac downregulated the anti-apoptotic proteins Bcl-xl and Mcl-1 and upregulated the pro-apoptotic proteins Bax and cellular stress proteins Bip, ATF-4, and PDI, in both cell lines. Sulindac downregulated expression of several epithelial-mesenchymal transition proteins in both cell lines, including beta-catenin, snail, and slug. Sulindac also downregulated expression of cell cycle proteins CDK4, CDK5, and Cyclin D1 and inflammatory protein COX-2 in both cell lines. After 4 wks of treatment, sulindac significantly inhibited tumor growth by 71% (1.89 g vs 0.54 g, p<0.01) in KpB mice. Conclusions: Our results find that sulindac exhibited anti-tumorigenic effects in OC cell lines and the KpB OC mouse model. Given these promising pre-clinical results, further studies on the repurposing of sulindac for the prevention and treatment of OC is warranted. Citation Format: Nikita Sinha, Shuning Chen, Jennifer Haag, Xiaochang Shen, Boer Deng, Ziyi Zhao, Chunxiao Zhou, Victoria Bae-Jump. Sulindac exhibits anti-proliferative effects in pre-clinical models of ovarian 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 5909.

Uterine serous carcinoma (USC) is a highly aggressive and frequently recurring subtype of endometrial cancer with limited treatment options for advanced or recurrent stages. Sulindac, a classic non-steroidal anti-inflammatory drug, has demonstrated anti-tumor activity in several pre-clinical tumor models. This study aims to evaluate the effect of sulindac on cell proliferation and invasion in USC cells. Human USC cell lines ARK-1 and SPEC2 were treated with different concentrations of sulindac. Cell proliferation was assessed using MTT and colony formation assays. ELISA assays measured cellular stress, cleaved caspase 3 activity, antioxidant ability, and adhesion. Cell cycle arrest was evaluated by Cellometer. The invasive capability was detected by wound healing assay. Western blotting was used to analyze the changes in protein expression induced by sulindac. Exposure to sulindac decreased cellular viability in a dose-dependent manner in ARK-1 and SPEC2 cells. Sulindac effectively inhibited cell cycle progression, increased cellular stress, caused apoptosis, and reduced cell adhesion and invasion in USC cells. Additionally, sulindac decreased the expression of COX-2 and blocked phosphorylation of NF-κB induced by TNF-α. Sulindac is a potential therapeutic agent for USC that deserves further exploration in pre-clinical studies and potentially future clinical trials.

Lipid metabolism is widely reprogrammed in tumor cells. Lipid droplet is a common organelle existing in most mammal cells, and its complex and dynamic functions in maintaining redox and metabolic balance, regulating endoplasmic reticulum stress, modulating chemoresistance, and providing essential biomolecules and ATP have been well established in tumor cells. The balance between lipid droplet formation and catabolism is critical to maintaining energy metabolism in tumor cells, while the process of energy metabolism affects various functions essential for tumor growth. The imbalance of synthesis and catabolism of fatty acids in tumor cells leads to the alteration of lipid droplet content in tumor cells. Diacylglycerol acyltransferase 1 and diacylglycerol acyltransferase 2, the enzymes that catalyze the final step of triglyceride synthesis, participate in the formation of lipid droplets in tumor cells and in the regulation of cell proliferation, migration and invasion, chemoresistance, and prognosis in tumor. Several diacylglycerol acyltransferase 1 and diacylglycerol acyltransferase 2 inhibitors have been developed over the past decade and have shown anti-tumor effects in preclinical tumor models and improvement of metabolism in clinical trials. In this review, we highlight key features of fatty acid metabolism and different paradigms of diacylglycerol acyltransferase 1 and diacylglycerol acyltransferase 2 activities on cell proliferation, migration, chemoresistance, and prognosis in tumor, with the hope that these scientific findings will have potential clinical implications.

Objective Interventions that combat obesity and its associated metabolic perturbations may decrease incidence and improve outcomes of endometrial cancer (EC). Potential options for weight loss include pharmacotherapeutic interventions such as tirzepatide, a dual-acting glucagon-like peptide 1 (GLP-1) and gastric inhibitory polypeptide (GIP) receptor agonist. Given this, we explored the anti-obesity and anti-tumorigenic effects of tirzepatide in our pre-clinical mouse model of endometrioid EC. Methods Starting at 4 weeks of age, Lkb1fl/flp53fl/fl mice were fed a low-fat diet vs a high-fat diet to generate a lean or obese phenotype. Nine weeks after induction of EC, obese and lean mice were randomized to receive tirzepatide for 4 weeks. Body and tumor weights, tumor transcriptomic and metabolomic profiles, and serum metabolic markers and chemokines were assessed. Results Both obese and lean mice began to lose body weight after 2 weeks of tirzepatide treatment, ultimately achieving a significant weight loss of 20.1 % in obese mice and 16.8 % in lean mice. Tirzepatide improved obesity-induced serum adiponectin, leptin, GIP, and C-reactive protein levels. Furthermore, tirzepatide relative to vehicle, effectively reduced tumor growth in obese and lean mice, inhibited the ErbB signaling and glycolysis/gluconeogenesis in tumors of obese mice, and increased O-linked glycosylation biosynthesis and phospholipase D signaling in tumors of lean mice. Conclusion Tirzepatide decreased both mouse weight and tumor growth via effects on metabolic and immune pathways in the EC tumors that differed between obese and lean mice. This novel weight loss treatment deserves further evaluation as an innovative strategy in the management of EC.

Objective Uterine serous carcinoma is a highly aggressive non-endometrioid subtype of endometrial cancer with poor survival rates overall, creating a strong need for new therapeutic strategies to improve outcomes. High-dose ascorbate (vitamin C) has been shown to inhibit cell proliferation and tumor growth in multiple preclinical models and has shown promising anti-tumor activity in combination with chemotherapy, with a favorable safety profile. We aimed to study the anti-tumor effects of ascorbate and its synergistic effect with carboplatin on uterine serous carcinoma cells. Methods Cell proliferation was evaluated by MTT and colony formation assays in ARK1, ARK2 and SPEC2 cells. Cellular stress, antioxidant ability, cleaved caspase 3 activity and adhesion were measured by ELISA assays. Cell cycle was detected by Cellometer. Invasion was measured using a wound healing assay. Changes in protein expression were determined by Western immunoblotting. Results High-dose ascorbate significantly inhibited cell proliferation, caused cell cycle arrest, induced cellular stress, and apoptosis, increased DNA damage, and suppressed cell invasion in ARK1 and SPEC2 cells. Treatment of both cells with 1 mM N-acetylcysteine reversed ascorbate-induced apoptosis and inhibition of cell proliferation. The combination of ascorbate and carboplatin produced significant synergistic effects in inhibiting cell proliferation and invasion, inducing cellular stress, causing DNA damage, and enhancing cleaved caspase 3 levels compared to each compound alone in both cells. Conclusions Ascorbate has potent antitumor activity and acts synergistically with carboplatin through its pro-oxidant effects. Clinical trials of ascorbate combined with carboplatin as adjuvant treatment of uterine serous carcinoma are worth exploring.

IntroductionEndometriosis (EM) is an aggressive, pleomorphic, and common gynecological disease. Its clinical presentation includes abnormal menstruation, dysmenorrhea, and infertility, which seriously affect the patient's quality of life. However, the pathogenesis underlying EM and associated regulatory genes are unknown. MethodsTelomere-related genes (TRGs) were uploaded from TelNet. RNA-sequencing (RNA-seq) data of EM patients were obtained from three datasets (GSE5108, GSE23339, and GSE25628) in the GEO database, and a random forest approach was used to identify telomere signature genes and build nomogram prediction models. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and Gene Set Enrichment Analysis were used to identify the pathways involved in the action of the signature genes. Finally, the CAMP database was used to screen drugs for potential use in EM treatment. ResultsFifteen total genes were screened as EM-telomere differentially expressed genes. Further screening by machine learning obtained six genes as characteristic predictive of EM. Immuno-infiltration analysis of the telomeric genes showed that expressions including macrophages and natural killer cells were significantly higher in cluster A. Further enrichment analysis showed that the differential genes were mainly enriched in biological pathways like cell cycle and extracellular matrix. Finally, the Connective Map database was used to screen 11 potential drugs for EM treatment. DiscussionTRGs play a crucial role in EM development, and are associated with immune infiltration and act on multiple pathways, including the cell cycle. Telomere signature genes can be valuable predictive markers for EM.

BACKGROUND:PHGDH (Phosphoglycerate Dehydrogenase) is the first branch enzyme in the serine biosynthetic pathway and plays a vital role in several cancers. However, little is known about the clinical significance of PHGDH in endometrial cancer.METHODS:Clinicopathological data of endometrial cancer were downloaded from the Cancer Genome Atlas database (TCGA). First, the expression of PHGDH in pan-cancer was investigated, as well as the expression and prognostic value of PHGDH in endometrial cancer. The effect of PHGDH expression on the prognosis of endometrial cancer was analyzed by Kaplan-Meier plotter and Cox regression. The relationship between PHGDH expression and clinical characteristics of endometrial cancer was investigated by logistic regression. Receiver operating characteristic (ROC) curves and nomograms were developed. Possible cellular mechanisms were explored using the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, the Gene Ontology (GO), and gene set enrichment analysis (GSEA). Finally, TIMER and CIBERSORT were used to analyze the relationship between PHGDH expression and immune infiltration. CellMiner™ was used to analyze the drug sensitivity of PHGDH.RESULTS:The results showed that PHGDH expression was significantly higher in endometrial cancer tissues than in normal tissues at mRNA and protein levels. Kaplan-Meier survival curves showed that patients in the high expression group had shorter overall survival (OS) and disease free survival (DFS) than patients in the low PHGDH expression group. Multifactorial COX regression analysis further supported that high PHGDH expression was an independent risk factor associated with prognosis in patients with endometrial cancer. The results showed estrogen response, mTOR, K-RAS, and epithelial mesenchymal transition (EMT) were differentially elevated in the high-expression group of the PHGDH group. CIBERSORT analysis showed that PHGDH expression is related to the infiltration of multiple immune cells. When PHGDH is highly expressed, the number of CD8+T cells decreases.CONCLUSION:PHGDH plays a vital role in the development of endometrial cancer, which is related to tumor immune infiltration, and can be used as an independent diagnostic and prognostic marker for endometrial cancer.

Abstract Background: Cuproptosis is a novel form of cell death, which is triggered by targeted mitochondria that bind the acylated lipid components of the tricarboxylic acid (TCA) cycle. Recent studies have suggested that targeting cuproptosis may be a new treatment strategy for cancer, but its association with cervcal cancer (CC) has not been elucidated. Methods: Data were downloaded from the TCGA-CESC. The cuproptosis-related lncRNAs were identified and prognostic risk models were constructed. Kaplan-Meier survival analysis, ROC curve, PCA and stratified analysis were used to validate the predictive ability of the model. A nomogram for predicting CC prognosis was established. The biological mechanisms associated with cuproptosis were investigated by GO and KEGG enrichment analysis. The CIBERSORT algorithm, immunoassay and TIDE score were used to measure different immune responses. Finally, we screened for sensitive drugs based on cuproptosis correlation. Results: We constructed a cuproptosis-related lncRNAs signature as a risk prognostic prediction model. The risk score was proved and the risk model had higher diagnostic efficiency than other features. The Kaplan-Meier curve indicated that lower risk score was significantly associated with better OS rate in training (P<0.001), testing group (P=0.004), and all groups (P<0.001). The time-dependent ROC curves showed the AUC reached 0.738 at 1 year, 0.698 at 3 years, and 0.699 at 5 years. GO and KEGG enrichment analysis found that the DEGs of low- and high-risk groups may be related to immune regulation. Further study of immune cell infiltration demonstrated that cuproptosis-related lncRNAs signature was significantly associated with the immune response of CC. A total of 23 drugs showed significant differences in the semi-inhibitory concentration (IC50) value, suggesting the signature may participate in the influence on drug efficacy. Conclusions: Our study reveals that assessing cuproptosis patterns in individual tumors will help improve our understanding of the immune mechanisms and prognosis of cervical cancer and thus guide immunotherapy more effectively. Establishing an independent prognostic model based on cuproptosis-associated lncRNAs could serve as a predictor of overall survival and also as a predictor of immunotherapy. The model may help provide personalized medical therapy and new insights into cancer treatment.

Endometriosis is a hormone-dependent disease in women of reproductive age and seriously affects women's health. To analyze the involvement of sex hormone receptors in endometriosis development, we performed bioinformatics analysis using four datasets derived from the Gene Expression Omnibus (GEO) database, which may help us understand the mechanisms by which the sex hormones act in vivo in endometriosis patients. The enrichment analysis and protein-protein interaction (PPI) analysis of the differentially expressed genes (DEGs) revealed that there are different key genes and pathways involved in eutopic endometrium aberrations of endometriosis patients and endometriotic lesions, and sex hormone receptors, including androgen receptor (AR), progesterone receptor (PGR) and estrogen receptor 1 (ESR1), may play important roles in endometriosis development. Androgen receptor (AR), as the hub gene of endometrial aberrations in endometriotic patients, showed positive expression in the main cell types for endometriosis development, and its decreased expression in the endometrium of endometriotic patients was also confirmed by immunohistochemistry (IHC). The nomogram model established based on it displayed good predictive value.