Objective: We investigated the clinical value of a novel circulating tumor cell (CTC) detection method-subtraction enrichment combined with immunostaining and fluorescence in situ hybridization (SEiFISH)-in ovarian cancer (OC). This study evaluated the diagnostic and prognostic significance of chromosome 8 aneuploidy in CTCs and circulating tumor endothelial cells (CTECs) for preoperative diagnosis, treatment efficacy assessment, and recurrence monitoring. Methods: A total of 331 patients were enrolled, including 56 with newly diagnosed primary OC, 265 with benign ovarian tumors, and 10 with borderline tumors. Peripheral blood CTCs and CTECs were detected using SEiFISH; their quantity and ploidy characteristics were analyzed in relation to clinical indicators. To assess dynamic CTC changes during disease progression and treatment response, 72 patients were followed longitudinally, of whom 19 experienced recurrence. Results: The CTC detection rate in OC patients was 92.9%, with significantly higher counts than that in the benign tumor group (median 5 vs. 2). Receiver operating characteristic analysis demonstrated good diagnostic performance for total CTCs [area under the curve (AUC)=0.699], with triploid CTCs achieving the highest efficacy (AUC=0.792), surpassing carbohydrate antigen 125 (CA125) (AUC=0.702). Postoperative follow-up showed that 70% of patients exhibited concurrent decreases in CTCs and CA125 levels, indicating disease improvement. In 30% of patients, CTC levels did not correlate with changes in CA125 levels. Individual case evidence suggests that CTC alterations may serve as an early indicator of recurrence or metastasis. Among the 19 recurrent cases, 73.7% showed elevated CTCs at recurrence that decreased following treatment. In four patients, CTCs reflected disease progression earlier than CA125, indicating higher sensitivity for recurrence monitoring. Conclusions: CTCs with chromosome 8 aneuploidy demonstrate significant clinical value in the preoperative diagnosis, treatment efficacy evaluation, and recurrence monitoring of OC. Dynamic CTC changes may serve as a more sensitive indicator than CA125 for disease surveillance, supporting the translational potential of CTC-based biomarkers in OC.
Background/Objectives: The diagnosis of endometriosis (EM) remains challenging due to the lack of a perfect diagnostic standard and the poor concordance between clinical symptoms and lesion severity. Although laparoscopy is widely used in clinical practice, it is invasive and associated with a non-negligible false-negative rate, while serum CA125 has limited diagnostic accuracy. In our previous studies, circulating endometrial cells (CECs) were identified in the peripheral blood of patients with EM, suggesting their potential as a non-invasive biomarker. Building on this finding, the present study aimed to systematically evaluate the clinical value of CECs in the diagnosis and stratified diagnosis of EM in the absence of a perfect diagnostic reference standard. Methods: Female patients treated at the Department of Obstetrics and Gynecology, Peking University People’s Hospital, between June 2022 and June 2024 were enrolled. Participants were clinically classified according to laparoscopic evaluation into an EM group and a non-EM group. However, laparoscopy was not treated as a definitive diagnostic gold standard in the statistical analysis. Instead, given the absence of a perfect reference standard, nonparametric latent class analysis was applied to jointly estimate disease status and the diagnostic performance of CECs, CA125, and laparoscopy. Patients with EM were further stratified according to dysmenorrhea severity (mild, moderate, and severe), lesion activity status (active or dormant), and menstrual cycle phase. Peripheral blood samples were collected from all participants, and CECs were detected using subtraction enrichment combined with immunofluorescence and fluorescence in situ hybridization (SE-iFISH). Serum CA125 levels were measured concurrently. Results: A total of 302 participants were included. The primary analysis focused on 133 surgically confirmed EM patients and 146 non-EM controls. After adjustment for an imperfect diagnostic reference standard, CECs demonstrated superior diagnostic performance compared with serum CA125 in the overall cohort, with higher sensitivity (0.58 vs. 0.37) and specificity (0.81 vs. 0.75). Under laparoscopic assessment in patients with severe dysmenorrhea (VAS ≥ 7), where the sensitivity and specificity were 0.759 and 1.00, respectively, CECs demonstrated superior diagnostic performance compared with serum CA125, with higher sensitivity (0.694 vs. 0.355) and specificity (0.946 vs. 0.429). Similarly, in patients with active EM, where laparoscopy showed a sensitivity of 0.79 and a specificity of 1.00, CECs again demonstrated superior diagnostic performance compared with CA125 (sensitivity 0.73 vs. 0.35; specificity 0.96 vs. 0.31), showing high concordance with laparoscopic diagnosis. When stratified by menstrual cycle phase, CECs maintained superior diagnostic performance over CA125 during both the proliferative and menstrual phases, with higher sensitivity (0.84 vs. 0.44) and specificity (0.83 vs. 0.65). Conclusions: Circulating endometrial cells (CECs) demonstrate high diagnostic accuracy for EM, significantly outperforming serum CA125, and show high concordance with laparoscopic diagnosis across clinically relevant stratified conditions in the absence of a perfect diagnostic gold standard.
Endometriosis is a common gynecological disorder characterized by the ectopic growth of endometrium-like tissue outside the uterine cavity and is associated with pelvic pain, infertility, and reduced quality of life. Although several theories have been proposed, the mechanisms by which endometrial cells disseminate and establish ectopic lesions remain incompletely understood. Here, we developed a dual-color pseudo-menstrual mouse model that enables real-time in vivo tracking of circulating endometrial cells (CECs) while distinguishing their tissue origin as uterine-derived or lesion-derived. Using in vivo flow cytometry and two-photon intravital microscopy, we found that both uterine-derived and lesion-derived CECs can enter the circulation and are detected at higher levels during menstruation-like breakdown, potentially in association with local vascular remodeling as suggested by intravital imaging observations. These cells could localize to distant organs, including the lungs and other extrapelvic organs. In addition, both CEC populations exhibited three distinct daily peak periods, and CEC dynamics were significantly associated with fluctuations in serum prolactin levels. In conclusion, these findings provide in vivo support for hematogenous dissemination in endometriosis and suggest that hormonal rhythmicity may regulate CEC dynamics, with potential diagnostic and therapeutic implications.
Although poly (ADP-ribose) polymerase inhibitors (PARPi) have been established to enhance ovarian cancer outcomes, the emergence of drug resistance poses considerable clinical challenges. In this study, we constructed a Hi-C atlas to systematically characterize the effect of olaparib on chromatin organization at multiple hierarchical scales, namely, chromosomes, A/B compartments, topologically associating domains, and chromatin loops. To investigate the effects of PARPi on expression of the cohesion subunit RAD21, we established olaparib-resistant ovarian cancer cell line. Furthermore, we examined the effects of RAD21 on the functions of ovarian cancer cells and spheroids based on cell proliferation, apoptosis, and comet assays. In addition, by performing integrated analyses using ChIP-seq datasets, ChIP-qPCR, and chromosome conformation capture assays, we assessed the influence of RAD21 on the enhancer–promoter interactions of a homologous recombination repair gene. Moreover, on the basis of our findings in previous studies using clinical samples, we further evaluated the clinical value of RAD21 in multiple databases. Genome-wide Hi-C heatmap analysis revealed that olaparib led to a reduction in the genome-wide contact frequency for long distance interactions, altered the degree of chromatin compartmentalization, and promoted compartment switching in ovarian cancer. Differences between the olaparib-treated and control cells with respect to topologically associating domain boundaries and chromatin loops were found to be associated with key cellular functions, such as DNA repair and transcriptional mis-regulation in cancer. Furthermore, PARPi treatment was observed to induce the expression of RAD21, whereas an upregulation of RAD21 promoted proliferation and inhibited apoptosis in ovarian cancer spheroids. Mechanistically, we obtained evidence to indicate that by maintaining enhancer–promoter interactions within chromatin conformation, RAD21 regulates the transcription of RAD51, thereby mediating olaparib resistance in ovarian cancer. The high expression of RAD21 was found to show a significant association with poor overall and progression-free survival in patients with ovarian cancer. Our findings in this study indicate that RAD21 could serve as a potential therapeutic target for overcoming olaparib resistance in ovarian cancer, and provide new insights into the mechanisms underlying the resistance to PARPi from the perspective of chromatin organization.
In recent years, mesenchymal stem cells (MSCs) have garnered significant attention as promising therapeutic tools for various diseases. To date, over ten MSC-based therapies have been approved and marketed worldwide, with their potential applications increasingly recognized. In gynecology, the exploration and clinical application of MSCs has advanced rapidly, with MSCs derived from diverse sources—including bone marrow, adipose tissue, menstrual blood, umbilical cord, umbilical cord blood, and placenta—undergoing extensive research and clinical trials. Due to their self-renewal, multidirectional differentiation, and immunomodulatory capabilities, MSCs offer promising prospects for treating gynecological diseases. MSCs are being explored for the treatment of various conditions, such as uterine adhesions, endometriosis, premature ovarian insufficiency, polycystic ovary syndrome, pelvic floor dysfunction, and gynecological tumors. Notably, MSC therapies for uterine adhesions and early-onset ovarian failure have progressed to clinical application, demonstrating notable efficacy. However, challenges remain in applying MSCs in gynecology, including cell source selection, standardization of preparation methods, and assessment of safety and efficacy. This review aims to systematically summarize the current status of MSC applications in gynecology, analyze existing challenges, and propose future directions for development. With advancements in technology and ongoing research, MSCs are expected to demonstrate broader applications in gynecological disease treatment, benefiting a larger number of patients.
Objective:The C-reactive protein-albumin-lymphocyte (CALLY) index serves as an integrated indicator, reflecting the interplay between systemic inflammation, immune competence, and nutritional health. While validated in other chronic diseases, its relevance to endometriosis remains unexplored. We aimed to assess its association with endometriosis using nationally representative data. Methods:This cross-sectional analysis used data from four cycles of the National Health and Nutrition Examination Survey (NHANES, 1999-2006), including 4,602 US adults. The CALLY index was derived by integrating measurements of C-reactive protein (CRP) levels, serum albumin concentrations, and lymphocyte counts. Associations with endometriosis were estimated using weighted multivariable logistic regression across three progressively adjusted models. The discriminatory ability of CALLY was assessed using receiver operating characteristic (ROC) analyses and compared against that of other commonly used inflammatory biomarkers. Smoothed curve fitting and subgroup/interaction analyses assessed pattern and heterogeneity. Results:Log-transformed CALLY values (ln CALLY) levels showed a statistically significant inverse relationship with endometriosis prevalence (OR = 0.87; 95% CI: 0.79-0.96). Individuals in the top quartile of ln CALLY (Q4) had a 40% lower risk of endometriosis than those in the bottom quartile (Q1) (OR = 0.60, 95% CI: 0.41-0.87). Compared to other commonly used indices, CALLY exhibited superior discriminatory performance, achieving an AUC of 0.7219 (95% CI: 0.6970-0.7468) in the fully adjusted model. Curve fitting indicated that higher CALLY index levels were linked to a reduced likelihood of endometriosis. Subgroup analysis further confirmed the consistency and independence of this relationship (all p values for interactions > 0.05). Conclusion:A significant inverse association was observed between the CALLY index and endometriosis prevalence among American adults, supporting its potential as a novel inflammatory marker for identifying individuals at elevated risk. However, as a cross-sectional study, causality cannot be inferred. Future prospective cohorts across diverse populations are needed to evaluate its clinical utility for risk prediction and early identification.
Background: To identify the metastatic lymph nodes and remove them accurately, the fluorescent surgical navigation ability of the ovarian cancer-specific fluorescent probe COC183B2-800 was assessed to verify the metastatic lymph nodes in the nude mouse model. Methods: The nude mouse model related to lymph node metastases in human ovarian cancer was established using the SKOV3-ip1 cell line. Besides, the COC183B2-800 probe (IRDye800CW Ester conjugated COC183B2 antibody) was fabricated. Moreover, in vivo fluorescence imaging was performed to determine the ability of the COC183B2-800 fluorescent probe to identify metastatic lymph nodes in the nude mouse model. Results: The nude mouse model related to lymph node metastases in human ovarian cancer was successfully established. In vivo fluorescence imaging was performed 30 hours after the injection of the COC183B2-800 fluorescent probe (25 μg) into the animal model, which can achieve specific imaging of metastatic lymph nodes. All metastatic lymph nodes were detected in vivo and in vitro (8/8), and only 1 negative lymph node with reactive enlargement showed a false positive fluorescent signal. Conclusions: The targeted fluorescent probe COC183B2-800 can be employed to identify metastatic lymph nodes in the nude mouse model related to lymph node metastases in human ovarian cancer with high specificity and sensitivity. Targeted fluorescence imaging using COC183B2-800 is expected to become a method to achieve precise lymphadenectomy.
Ovarian endometriosis is characterized by the growth of endometrial tissue within the ovary, causing infertility and chronic pain. However, its pathophysiology remains unclear. Utilizing high-precision single-cell RNA sequencing, we profile the normal, eutopic, and ectopic endometrium from 34 individuals across proliferative and secretory phases. We observe an increased proportion of ciliated cells in both eutopic and ectopic endometrium, characterized by a diminished expression of estrogen sulfotransferase, which likely confers apoptosis resistance. After translocating to ectopic lesions, endometrial epithelium upregulates nicotinamide N-methyltransferase expression that inhibits apoptosis by promoting deacetylation and subsequent nuclear exclusion of transcription factor forkhead box protein O1, thereby leading to the downregulation of the apoptotic gene BIM. Moreover, epithelial cells in ectopic lesions elevate HLA class II complex expression, which stimulates CD4+ T cells and consequently contributes to chronic inflammation. Altogether, our study provides a comprehensive atlas of ovarian endometriosis and highlights potential therapeutic targets for modulating apoptosis and inflammation.
BackgroundPelvic pain is a common complaint of discomfort in women, with an increasing incidence and seriously affecting patients’ quality of life. Its etiology involves multiple systems and disciplines, and therefore treatment modalities are diverse. Transcutaneous electrical acupoint stimulation (TEAS) therapy is a classic analgesic means, and electrical stimulation of local acupoints can achieve obvious analgesic effects. This review aims to discuss the application of TEAS for the treatment of various types of pelvic pain, the selection of optimal parameters and the renewal of equipment.MethodResultTEAS for treatment of pelvic pain in women has been reported mainly for endometriosis, pelvic inflammatory disease (PID), intrauterine adhesion (IUA), pelvic stasis syndrome, interstitial cystitis, primary dysmenorrhoea and other diseases. And for parameter selection, the most used of frequency is dilatational wave, the most used stimulation intensity is 10–20 mA, and the acupoint selection should be based on the specific conditions of the patient.ConclusionsThe analgesic mechanism of TEAS has not been fully elucidated, but the efficacy of the treatment is remarkable and there are no significant adverse effects. The selection of the parameters for TEAS and the combination of acupoints for different pains are still the main directions of future research.
Near-infrared fluorescence (NIRF) imaging is an excellent choice for image-guided surgery due to its simple operation and non-invasiveness. Developing tumor-specific fluorescent molecular probes is key to fluorescence imaging-guided surgery. EGFR (epidermal growth factor receptor) is closely related to the proliferation and growth of tumor cells and is highly expressed in epithelial ovarian cancer (EOC). The study aims to construct a NIR fluorescent molecular probe using cetuximab (an EGFR monoclonal antibody) and investigate its feasibility for targeting EOC in vivo through fluorescence imaging. We determined the expression of EGFR in EOC. NIR fluorescent molecular probe with cetuximab (cetuximab-Cy7) was chemically engineered and identified. The subcutaneous xenografted tumor model of EOC was induced using SKOV3-Luc cell line with positive expression of EGFR. Cetuximab-Cy7 was used for in vivo fluorescence imaging, and phosphate-buffered saline, free Cy7 dye and mouse isotype immunoglobulin G-Cy7 were used as controls. NIRF imaging system was performed to study the distribution and targeting of the probes. Tumors were imaged in situ and ex vivo, and fluorescent intensity was quantified. Resected specimens were analyzed to confirm diagnosis, and immunohistochemical (IHC) staining was used to identify EGFR expression. EGFR expression was increased in EOC tissues than fallopian tube tissues. The high expression of EGFR was significantly correlated with well-differentiation, residual lesions ≤ 1 cm, no recurrence and increased survival. NIRF imaging showed that the cetuximab-Cy7 enabled detection of tumor lesions in EOC-bearing mice with the optimal dose of 30 µg. The suitable imaging time window may be 24–96 h post-injection. Ex vivo fluorescence imaging indicated that fluorescent signal was mainly detected in the tumor and the lung. IHC results confirmed that xenografts were EGFR positive. Cetuximab-Cy7 can specifically target the tumors of EOC xenografted nude mice. This research lays the foundation for future studies on EOC surgery navigation.
Extracellular matrix protein 1 (ECM1) is a glycoprotein that may be a key player in tumorigenesis and tumor progression. However, knowledge regarding the role of ECM1 in endometriosis (EM) is still lacking. Microarray analyses were performed to compare the mRNA expression patterns between paired EU tissues and ectopic endometrial (EC) tissues (n = 4) from EM patients. ECM1 expression was significantly increased in the eutopic endometrial (EU) tissues than paired EC tissues of endometriotic patients and normal endometrial (NE) tissues of controls without EM. Blocking ECM1 with siRNA attenuated the migration and invasion of hEM15A cells and modified the distribution of the F-actin cytoskeleton. We conducted microarray analyses and bioinformatics analyses to investigate the differentially expressed genes (DEGs) and related pathways regulated by ECM1. A total of 161 DEGs between the siECM1 and the negative control (siNC) treatments were identified, consisting of 79 downregulated genes and 82 upregulated genes. Enriched DEGs were associated with 9 gene ontology (GO) terms. Moreover, a protein-protein interaction (PPI) network was constructed for the hub genes and modules. Radixin (RDX) was the second most downregulated gene in the siECM1 group compared with the siNC group. ECM1 knockdown significantly decreased the expression of RDX, RhoC, ROCK1, N-cadherin and β-catenin but not ROCK2. ECM1 showed high tissue-specific expression in EU tissues from EM patients, and may contribute to the migration, invasion and reorganization of the F-actin cytoskeleton in eutopic endometrial stromal cells via the RhoC/ROCK1 signaling pathway in EM.
A 25-year-old nulliparous woman presented with ascites and pleural effusion for 2 months detected by multiple imaging tests (Fig. 1). She reported progressive dysmenorrhea in the past 10 years and denied other obvious symptoms. Her medical history included a thoracoscopic bullae resection performed six years ago due to spontaneous recurrent pneumothorax, pathology of which demonstrated chronic inflammatory and fibrotic changes and no signs of malignancy. One month after this surgery, the patient suffered another pneumothorax and achieved remission with conservative treatment. Since then, the patient has not experienced any severe chest symptoms and has not undergone any further reviews. Through meticulous inquiry into the patient's menstrual cycle during each pneumothorax episode, our gynecologist ascertained that every attack coincided with the patient's menstrual period and diagnosed the patient with catamenial pneumothorax. For further diagnosis and treatment, a multi-team surgery involving the gynecologist and the thoracic surgeon was performed. On the day of the operation, right-sided thoracoscopic surgery revealed extensive pleural adhesions, a large amount of hemorrhagic pleural effusion, and numerous dark brown nodules densely distributed on the parietal pleura (Fig. 2). 800 mL pleural effusion was drained and nodules were biopsied. Subsequently, laparoscopy revealed a massive pool of bloody ascitic fluid in the pelvic cavity. After suction of about 400ml ascites, pelvic endometriosis lesions were more clearly observed, including blisters approximately 0.5-2 cm in size on the surface of the uterus and chocolate cysts in bilateral ovaries. The patient then underwent bilateral ovarian cystectomy and electrocautery of peritoneal endometriosis. Figure. 2Operative findings during thoracoscopy (A-D). Massive hemorrhagic pleural fluid (Panel A, asterisk); minimal red endometriotic lesions on the thoracic wall (Panel B, arrows); dark brown nodules scattered on the parietal pleura (Panel C, asterisk); extensive pleural adhesions (Panel D, asterisk). View Large Image Figure Viewer Download Hi-res image
This study aimed to develop and evaluate radiomics models to predict CD27 expression and clinical prognosis before surgery in patients with serous ovarian cancer (SOC). We used transcriptome sequencing data and contrast-enhanced computed tomography images of patients with SOC from The Cancer Genome Atlas (n = 339) and The Cancer Imaging Archive (n = 57) and evaluated the clinical significance and prognostic value of CD27 expression. Radiomics features were selected to create a recursive feature elimination-logistic regression (RFE-LR) model and a least absolute shrinkage and selection operator logistic regression (LASSO-LR) model for CD27 expression prediction. CD27 expression was upregulated in tumor samples, and a high expression level was determined to be an independent protective factor for survival. A set of three and six radiomics features were extracted to develop RFE-LR and LASSO-LR radiomics models, respectively. Both models demonstrated good calibration and clinical benefits, as determined by the receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis. The LASSO-LR model performed better than the RFE-LR model, owing to the area under the curve (AUC) values of the ROC curves (0.829 vs. 0.736). Furthermore, the AUC value of the radiomics score that predicted the overall survival of patients with SOC diagnosed after 60 months was 0.788 using the LASSO-LR model. The radiomics models we developed are promising noninvasive tools for predicting CD27 expression status and SOC prognosis. The LASSO-LR model is highly recommended for evaluating the preoperative risk stratification for SOCs in clinical applications.
BACKGROUND:Extracellular adenosine triphosphate (eATP) is an important inflammatory mediator that can boost the antitumour immune response, but its role in endometriosis remains unknown. We hypothesized that eATP could inhibit endometriosis cell function both directly and indirectly through macrophages.METHODS:Peritoneal and cyst fluid from endometriosis patients and non-endometriosis controls was collected to measure eATP levels. The addition of eATP was performed to explore its effects on endometriotic cell and macrophage functions, including cell proliferation, apoptosis, pyroptosis, mitochondrial membrane potential, phagocytosis, and the production of inflammatory cytokines and reactive oxygen species. A coculture of endometriotic epithelial cells and U937 macrophages was established, followed by P2X7 antagonist and eATP treatment. Endometriosis model eATP-treated rats were used to evaluate in situ cell death and macrophage marker expression.RESULTS:The pelvic microenvironment of endometriosis patients shows high eATP levels, which could induce endometriotic epithelial cell apoptosis and pyroptosis and significantly inhibit cell growth via the MAPK/JNK/Akt pathway. eATP treatment ameliorated endometriosis-related macrophage dysfunction and promoted macrophage recruitment. eATP treatment in the presence of macrophages exerted a stronger cytotoxic effect on endometriotic epithelial cells by regulating P2X7. eATP treatment effectively induced cell death in an endometriosis rat model and prominently increased the macrophage number without affecting the eutopic endometrium.CONCLUSION:eATP induces endometriotic epithelial cell death and enhances the immune function of macrophages to inhibit the progression of endometriosis, while eutopic endometrium is not affected. eATP treatment may serve as a nonhormonal therapeutic strategy for endometriosis.
BACKGROUND:Endometriosis (EM) is a complex benign gynecological disease, but it has malignant biological behavior and can invade any part of the body. Clinical manifestations include pelvic pain, dysmenorrhea, infertility, pelvic nodules, and masses. Our previous study successfully detected circulating endometrial cells (CECs) in the peripheral blood of patients with EM. The purpose of this study is to overcome the limitation of cell size in the previous microfluidic chip method, to further accurately capture CECs, understand the characteristics of these cells, and explore the relationship between CECs and the clinical course characteristics of patients with EM. METHODS:Human peripheral venous blood used to detect CECs and circulating vascular endothelial cells (CVECs) was taken from EM patients ( n = 34) hospitalized in the Peking University People's Hospital. We used the subtraction enrichment and immunostaining fluorescence in situ hybridization (SE-iFISH) method to exclude the interference of red blood cells, white blood cells, and CVECs, so as to accurately capture the CECs in the peripheral blood of patients with EM. Then we clarified the size and ploidy number of chromosome 8 of CECs, and a second grouping of patients was performed based on clinical characteristics to determine the relationship between CECs and clinical course characteristics. RESULTS:The peripheral blood of 34 EM patients and 12 non-EM patients was evaluated by SE-iFISH. Overall, 34 eligible EM patients were enrolled. The results showed that the detection rates of CECs were 58.8% in EM patients and 16.7% in the control group. However, after classification according to clinical characteristics, more CECs could be detected in the peripheral blood of patients with rapidly progressive EM, with a detection rate of 94.4% (17/18). In total, 63.5% (40/63) of these cells were small cells with diameters below 5 μm, and 44.4% (28/63) were aneuploid cells. No significant association was found between the number of CECs and EM stage. CONCLUSION:The number and characteristics of CECs are related to the clinical course characteristics of patients with EM, such as pain and changes in lesion size, and may be used as biomarkers for personalized treatment and management of EM in the future.
Background The dysfunction of the immune system is one of the pathogeneses of endometriosis. Immune cells can not only affect the microenvironment of the endometrium by secreting cytokines and defensins but also promote angiogenesis, growth and invasion of endometrial stromal cells.Result ATP is a key mediator in the immune mechanism of endometriosis and plays a crucial role in endometriosis. While ATP acts as a purinergic signalling molecule, it has a close relationship with the pain of endometriosis via activating ATP receptors, including P2X3, P2X4, P2X7 and P2Y receptors, after being activated by the immune system. Besides, ATP levels reflect the impairment of mitochondrial function in granulosa cells, which could lead to infertility. The modulation of ATP expression levels is controlled by ectonucleotidases. The content of ectonucleotidases is altered in endometriosis which may be emerging non-invasive biomarkers.Conclusion In the present review, we briefly introduce the relationship between the change of ATP level controlled by ectonucleotidases and endometriosis-associated infertility and pain, and illustrate our prospects for future research.
High malignancy is a prominent characteristic of epithelial ovarian cancer (EOC), emphasizing the necessity for further elucidation of the potential mechanisms underlying cancer progression. Aneuploidy and copy number variation (CNV) partially contribute to the heightened malignancy observed in EOC; however, the precise features of aneuploidy and their underlying molecular patterns, as well as the relationship between CNV and aneuploidy in EOC, remain unclear. In this study, we employed single-cell sequencing data along with The Cancer Genome Atlas (TCGA) to investigate aneuploidy and CNV in EOC. The technique of fluorescence in situ hybridization (FISH) was employed using specific probes. The copy number variation within the genomic region of chromosome 8 (42754568-47889815) was assessed and utilized as a representative measure for the ploidy status of individual cells in chromosome 8. Differential expression analysis was performed between different subgroups based on chromosome 8 ploidy. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), protein–protein interaction (PPI), and hub–gene analyses were subsequently utilized to identify crucial genes involved. By classifying enriched tumor cells into distinct subtypes based on chromosome 8 ploidy combined with TCGA data integration, we identified key genes driving chromosome 8 aneuploidy in EOC, revealing that PRKDC gene involvement through the mediated non-homologous end-joining pathway may play a pivotal role in disease progression. Further validation through analysis of the GEO and TCGA database and survival assessment, considering both mRNA expression levels and CNV status of PRKDC, has confirmed its involvement in the progression of EOC. Further functional analysis revealed an upregulation of PRKDC in both ovarian EOC cells and tissues, with its expression showing a significant correlation with the extent of copy number variation (CNV) on chromosome 8. Taken together, CNV amplification and aneuploidy of chromosome 8 are important characteristics of EOC. PRKDC and the mediated NHEJ pathway may play a crucial role in driving aneuploidy on chromosome 8 during the progression of EOC.
•Women conceived with adenomyosis were of higher age, BMI, ART ratio, and higher rate of concurrent UL.•Women with adenomyosis have a higher risk of many adverse pregnancy outcomes.•ART may further increase the risk of hypertensive disorder and PPH.•Uterine leiomyoma of which the diameter≥4 cm may increase the risk of severe PPH.
BACKGROUND:High-grade serous ovarian cancer (HGSOC) is the biggest cause of gynecological cancer-related mortality because of its extremely metastatic nature. This study aimed to explore and evaluate the characteristics of candidate factors associated with the metastasis and progression of HGSOC.METHODS:Transcriptomic data of HGSOC patients' samples collected from primary tumors and matched omental metastatic tumors were obtained from three independent studies in the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were selected to evaluate the effects on the prognosis and progression of ovarian cancer using data from The Cancer Genome Atlas (TCGA) database. Hub genes' immune landscapes were estimated by the Tumor Immune Estimation Resource (TIMER) database. Finally, using 25 HGSOC patients' cancer tissues and 10 normal fallopian tube tissues, immunohistochemistry (IHC) was performed to quantify the expression levels of hub genes associated with International Federation of Gynecology and Obstetrics (FIGO) stages.RESULTS:Fourteen DEGs, ADIPOQ , ALPK2 , BARX1 , CD37 , CNR2 , COL5A3 , FABP4 , FAP , GPR68 , ITGBL1 , MOXD1 , PODNL1 , SFRP2 , and TRAF3IP3 , were upregulated in metastatic tumors in every database while CADPS , GATA4 , STAR , and TSPAN8 were downregulated. ALPK2 , FAP , SFRP2 , GATA4 , STAR , and TSPAN8 were selected as hub genes significantly associated with survival and recurrence. All hub genes were correlated with tumor microenvironment infiltration, especially cancer-associated fibroblasts and natural killer (NK) cells. Furthermore, the expression of FAP and SFRP2 was positively correlated with the International Federation of Gynecology and Obstetrics (FIGO) stage, and their increased protein expression levels in metastatic samples compared with primary tumor samples and normal tissues were confirmed by IHC ( P = 0.0002 and P = 0.0001, respectively).CONCLUSIONS:This study describes screening for DEGs in HGSOC primary tumors and matched metastasis tumors using integrated bioinformatics analyses. We identified six hub genes that were correlated with the progression of HGSOC, particularly FAP and SFRP2 , which might provide effective targets to predict prognosis and provide novel insights into individual therapeutic strategies for HGSOC.
子宫内膜异位症是指子宫内膜组织在子宫腔被覆内膜以外的部位出现、生长、浸润,继而导致慢性盆腔疼痛、盆腔肿块和不孕等症状.子宫内膜异位症是常见的妇科良性疾病,育龄期女性发病率约为10%.子宫内膜异位症最常发生于盆腔器官和腹膜,极少部分也出现在盆腔以外部位,引起不同的临床症状.