{"title":"Drug-free in vitro activation combined with ADSCs-derived exosomes restores ovarian function of rats with premature ovarian insufficiency.","authors":"Qian Li, Zhiqiang Zhang, Wenxin Shi, Zhongkang Li, Yanlai Xiao, Jingkun Zhang, Xianghua Huang","doi":"10.1186/s13048-024-01475-4","DOIUrl":"10.1186/s13048-024-01475-4","url":null,"abstract":"<p><strong>Background: </strong>Drug-free in vitro activation (IVA) is a new protocol to activate residual dormant follicles for fertility restoration in patients with premature ovarian insufficiency (POI). However, several deficiencies have reduced its clinical efficacy rate. Our previous studies have confirmed that the combination of adipose-derived stem cells (ADSCs) and drug-free IVA can improve the effectiveness of drug-free IVA and restore ovarian function of rats with POI. Increasing evidence has demonstrated that mesenchymal stem cell-derived exosomes have similar therapeutic effects as their source cells. Here, we performed a preclinical study to evaluate the therapeutic effects of ADSCs-derived exosomes (ADSCs-Exos) combined with drug-free IVA in the POI rats and the mechanism in restoring ovarian function.</p><p><strong>Results: </strong>In vivo, the effects of ADSCs-Exos were comparable to those of ADSCs, and the ADSCs-Exos combined with drug-free IVA was better than ADSCs-Exos alone therapy in promoting follicular development. Moreover, transplantation of ADSCs/ADSCs-Exos lead to up-regulation of BCL-2 expression and down-regulation of the expression of Bax and Cleaved Caspase-3, thus reducing the apoptosis of chemotherapy-induced follicle cells, and further promoting the development of the follicles and rescuing ovarian function in POI-damaged ovary. In vitro, ovarian fragmentation could activate follicular growth and development, and in combination with ADSCs-Exos could prevent the loss of follicles, promote follicular proliferation and inhibit apoptosis.</p><p><strong>Conclusions: </strong>ADSCs-Exos combined drug-free IVA had remarkable therapeutic effects in restoring ovarian function of POI rats, and markedly promoted follicular development and inhibited apoptosis of ovarian cells in vitro. Our study confirmed that the combination therapy might be a promising and effective treatment for POI.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"17 1","pages":"158"},"PeriodicalIF":3.8,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11290131/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141860105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hadis Hooshmandi, Akram Ghadiri-Anari, Ali Mohammad Ranjbar, Hossein Fallahzadeh, Mahdieh Hosseinzadeh, Azadeh Nadjarzadeh
{"title":"Effects of licorice extract in combination with a low-calorie diet on obesity indices, glycemic indices, and lipid profiles in overweight/obese women with polycystic ovary syndrome (PCOS): a randomized, double-blind, placebo-controlled trial.","authors":"Hadis Hooshmandi, Akram Ghadiri-Anari, Ali Mohammad Ranjbar, Hossein Fallahzadeh, Mahdieh Hosseinzadeh, Azadeh Nadjarzadeh","doi":"10.1186/s13048-024-01446-9","DOIUrl":"10.1186/s13048-024-01446-9","url":null,"abstract":"<p><strong>Background: </strong>Polycystic ovary syndrome (PCOS) is the most common ovarian dysfunction. Recent studies showed the effectiveness of licorice on metabolic profiles with inconsistent findings. So, we investigated the effect of licorice on obesity indices, glycemic indices, and lipid profiles in women with PCOS.</p><p><strong>Methods: </strong>This randomized, double-blind, placebo-controlled trial was performed on 66 overweight/obese women with PCOS. The participants were randomly assigned to receive either 1.5 gr/day licorice extract plus a low-calorie diet (n = 33) or placebo plus a low-calorie diet (n = 33) for 8 weeks. Participants' anthropometric indices and body composition were assessed using standard protocols. Fasting blood sugar (FBS), insulin levels, low-density lipoprotein-cholesterol (LDL-C), total cholesterol (TC), triglyceride (TG), and high-density lipoprotein-cholesterol (HDL-C) were measured using enzymatic kits. The homeostasis model assessment-insulin resistance (HOMA-IR) and HOMA of β-cell function (HOMA-B) were calculated using valid formulas.</p><p><strong>Results: </strong>Between-group comparisons demonstrated significant differences between the groups in terms of obesity indices (body weight, BMI, and body fat), lipid profiles (TG, TC, LDL-C, and HDL-C), FBS and insulin levels, HOMA-IR, and HOMA-B at the end of the study (P < 0.05). Supplementation with licorice plus a low-calorie diet was also more effective in improving all parameters than a low-calorie diet alone after adjusting for confounders (baseline values, age, weight changes, and physical activity changes) (P < 0.05).</p><p><strong>Conclusion: </strong>The findings showed that licorice consumption leads to improvements in obesity indices, glucose homeostasis, and lipid profiles compared to placebo. Due to possible limitations of the study, further research is needed to confirm these findings.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"17 1","pages":"157"},"PeriodicalIF":3.8,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11287987/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141855799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Correction: Metformin modifies plasma microbial-derived extracellular vesicles in polycystic ovary syndrome with insulin resistance","authors":"Liping Hu, Guolin Hong, Jingzhi Li, Mengkun Chen, Chih-Jung Chang, Po-Jen Cheng, Zhimei Zhang, Xinli Zhang, Huiping Chen, Yingting Zhuang, Yuqin Li","doi":"10.1186/s13048-024-01481-6","DOIUrl":"https://doi.org/10.1186/s13048-024-01481-6","url":null,"abstract":"<p><b>Correction: J Ovarian Res 17, 136 (2024)</b></p><p><b>https://doi.org/10.1186/s13048-024-01444-x</b></p><p>Following publication of the original article [1], the authors reported that affiliations of author ‘Guolin Hong’ and affiliation 3 were incorrectly presented. The author group is presented correctly in this correction article.</p><p>The original article [1] has been corrected.</p><ol data-track-component=\"outbound reference\" data-track-context=\"references section\"><li data-counter=\"1.\"><p>Hu L, Hong G, Li J, et al. Metformin modifies plasma microbial-derived extracellular vesicles in polycystic ovary syndrome with insulin resistance. J Ovarian Res. 2024;17:136. https://doi.org/10.1186/s13048-024-01444-x.</p><p>Article CAS PubMed PubMed Central Google Scholar </p></li></ol><p>Download references<svg aria-hidden=\"true\" focusable=\"false\" height=\"16\" role=\"img\" width=\"16\"><use xlink:href=\"#icon-eds-i-download-medium\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"></use></svg></p><h3>Authors and Affiliations</h3><ol><li><p>Department of Laboratory Medicine, Xiamen Chang Gung Hospital Hua Qiao University, Xiamen, 361028, P. R. China</p><p>Liping Hu & Zhimei Zhang</p></li><li><p>The Third Clinical Medical College, Fujian Medical University, Fuzhou, P. R. China</p><p>Liping Hu</p></li><li><p>Department of Laboratory Medicine, Xiamen Key Laboratory of Genetic Testing, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, 361005, P. R. China</p><p>Guolin Hong</p></li><li><p>Department of Obstetrics, Xiangya Hospital Central South University, Changsha, P. R. China</p><p>Jingzhi Li</p></li><li><p>Department of Gynecology and Obstetrics, Xiamen Chang Gung Hospital Hua Qiao University, Xiamen, P. R. China</p><p>Mengkun Chen, Po-Jen Cheng, Xinli Zhang, Huiping Chen & Yuqin Li</p></li><li><p>School of Medicine, Hua Qiao University, Quanzhou, P. R. China</p><p>Chih-Jung Chang</p></li><li><p>School of Pharmacy, Fujian Medical University, Fuzhou, P. R. China</p><p>Yingting Zhuang</p></li><li><p>Medical Research Center, Xiamen Chang Gung Hospital Hua Qiao University, Xiamen, P. R. China</p><p>Chih-Jung Chang</p></li><li><p>Drug Hypersensitivity Clinical and Research Center, Department of Dermatology, Chang Gung Memorial Hospital, Taoyuan, Linkou, Taiwan</p><p>Chih-Jung Chang</p></li></ol><span>Authors</span><ol><li><span>Liping Hu</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Guolin Hong</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Jingzhi Li</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Mengkun Chen</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><spa","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"70 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141780873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Riya Khetan, Preethi Eldi, Noor A. Lokman, Carmela Ricciardelli, Martin K. Oehler, Anton Blencowe, Sanjay Garg, Katherine Pillman, Hugo Albrecht
{"title":"Unveiling G-protein coupled receptors as potential targets for ovarian cancer nanomedicines: from RNA sequencing data analysis to in vitro validation","authors":"Riya Khetan, Preethi Eldi, Noor A. Lokman, Carmela Ricciardelli, Martin K. Oehler, Anton Blencowe, Sanjay Garg, Katherine Pillman, Hugo Albrecht","doi":"10.1186/s13048-024-01479-0","DOIUrl":"https://doi.org/10.1186/s13048-024-01479-0","url":null,"abstract":"Genetic heterogeneity in ovarian cancer indicates the need for personalised treatment approaches. Currently, very few G-protein coupled receptors (GPCRs) have been investigated for active targeting with nanomedicines such as antibody-conjugated drugs and drug-loaded nanoparticles, highlighting a neglected potential to develop personalised treatment. To address the genetic heterogeneity of ovarian cancer, a future personalised approach could include the identification of unique GPCRs expressed in cancer biopsies, matched with personalised GPCR-targeted nanomedicines, for the delivery of lethal drugs to tumour tissue before, during and after surgery. Here we report on the systematic analysis of public ribonucleic acid-sequencing (RNA-seq) gene expression data, which led to prioritisation of 13 GPCRs as candidates with frequent overexpression in ovarian cancer tissues. Subsequently, primary ovarian cancer cells derived from ascites and ovarian cancer cell lines were used to confirm frequent gene expression for the selected GPCRs. However, the expression levels showed high variability within our selection of samples, therefore, supporting and emphasising the need for the future development of case-to-case personalised targeting approaches.","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"425 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141780872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Effects of mind-body interventions on polycystic ovary syndrome: a comprehensive meta-analysis.","authors":"Kun Zhao, Liuyan Nie, Xiangming Ye, Xiaoyan Hu","doi":"10.1186/s13048-024-01477-2","DOIUrl":"10.1186/s13048-024-01477-2","url":null,"abstract":"<p><strong>Background: </strong>Mind-body interventions (MBI) have emerged as a potential therapeutic approach, but their effectiveness in the treatment of Polycystic Ovary Syndrome (PCOS) remains inconclusive. This study systematically evaluates the effectiveness of MBI on quality of life, anthropometry, androgen secretion, glucose, and lipid metabolism in PCOS.</p><p><strong>Methods: </strong>A computer search was conducted across three databases: PubMed, the Cochrane Library, and EMBASE, to identify randomized controlled trials (RCTs) related to MBI for PCOS from their inception until July 2024. DerSimonian and Laird's random-effects model and Stata 17.0 software was employed for our meta-analysis.</p><p><strong>Results: </strong>Twelve RCTs were included. MBI significantly improved PCOSQ subscale scores, including emotional disturbances (MD: 7.75, 95% CI: 6.10 to 9.40), body hair (MD: 2.73, 95% CI: 0.54 to 4.91), menstrual problems (MD: 3.79, 95% CI: 2.89 to 4.69), and weight (MD: 1.48, 95% CI: 0.03 to 2.93). Furthermore, there was a reduction in depression levels (MD: -1.53, 95% CI: -2.93 to -0.13). Sensitivity analysis confirmed the robustness of PCOSQ-Emotional disturbances and PCOSQ-Menstrual problems, with a high GRADE level of evidence for these subscales. Secondary outcome measures, including waist-hip ratio, fasting blood glucose, and HOMA-IR exhibited statistically significant differences. Subgroup analysis revealed that obesity could influence treatment outcomes.</p><p><strong>Conclusion: </strong>MBI can serve as an alternative therapy, modulating effect on the quality of life and depression in PCOS patients. Future well-designed, high-quality, and large-scale studies should be conducted to thoroughly assess the impact of different Mind-Body Interventions (MBI) on various PCOS phenotypes.</p><p><strong>Trial registration: </strong>PROSPERO (CRD42023472035).</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"17 1","pages":"154"},"PeriodicalIF":3.8,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11271059/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141759323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Hsa_circ_0043532 contributes to PCOS through upregulation of CYP19A1 by acting as a ceRNA for hsa-miR-1270","authors":"Huimin Zhang, Jianye Fang, Yingxue Liu, Wenqian Zhu, Yangying Xu, Yu Zhang, Wei Shen, Duan Li, Cuifang Hao","doi":"10.1186/s13048-024-01474-5","DOIUrl":"https://doi.org/10.1186/s13048-024-01474-5","url":null,"abstract":"Polycystic ovarian syndrome (PCOS) accounts for about 75% of anovulatory infertility. The cause of PCOS is not clear. CircRNAs acting as miRNA sponges mediate the post-transcriptional regulation of multiple genes. CYP19A1 is a limiting enzyme in the ovarian steroidogenesis pathway. However, the mechanism of circRNAs regulating granulosa cell (GC) estradiol secretion in PCOS remains to be elucidated. Bioinformatics was used to predict the potential target miRNAs of circ_0043532 and target genes of miR-1270. Target miRNAs and mRNA expression were verified by qRT-PCR in GCs from 45 women with PCOS and 65 non-PCOS. Western blot, ELISA and dual-luciferase reporter assays were applied to confirm the substrate of miR-1270. Circ_0043532 and CYP19A1 were significant up-regulation in GCs from patients with PCOS. The predicted target miRNAs of circ_0053432, miR-1270, miR-576-5p, miR-421 and miR-142-5p, were notably decreased in GCs from patients with PCOS. Mechanistic experiments showed that circ_0043532 specifically binds to miR-1270. MiR-1270 was negatively regulated by circ_0043532. Concomitantly, miR-1270 inhibited CYP19A1 expression and estradiol production, which could be reversed by circ_0043532 over-expression. We identified that circ_0043532/miR-1270/CYP19A1 axis contributes to the aberrant steroidogenesis of GCs from patients with PCOS. This study broadens the spectrum of pathogenic factors of PCOS, and circ_0043532 might be a potential therapeutic target for PCOS.","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"345 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141745558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The natural menstrual cycle revisited – can natural cycle be trusted","authors":"B Alsbjerg, US Kesmodel, P Humaidan, L Bungum","doi":"10.1186/s13048-024-01469-2","DOIUrl":"https://doi.org/10.1186/s13048-024-01469-2","url":null,"abstract":"The serum progesterone (P4) level during the luteal phase (LP) plays a crucial role in the initiation and maintenance of pregnancy. However, it is unclear whether the natural cycle consistently provides the best endocrine profile and whether mid-luteal serum P4 levels are always sufficient to support implantation and early pregnancy. The question has become more relevant in relation to fertility treatment, as more frozen embryo transfer cycles are performed in the natural cycle. Moreover, can serum hormone levels and covariates measured during the follicular phase (FP), such as Follicle Stimulation Hormone (FSH), Luteinizing Hormone (LH), Estradiol (E2), Anti-Mullerian Hormone (AMH) and Antral Follicle Count (AFC), be used to predict P4 levels during the luteal phase (LP)? This observational prospective cohort study analysed 26 healthy women with a cycle length between 21–35 days and a body mass index (BMI) < 30 kg/m2. Blood sampling started on the fifth day of the menstrual cycle and continued every fifth day until the next cycle. The procedure was repeated for a total of three cycles. The study found that only ten women had a P4 level greater than 30 nmol/L on cycle day 20 or 25 in all three cycles. In total, only 45 cycles out of 77 cycles had serum P4 levels ≥ 30 nmol/L. The E2 level ≥ 345 pmol/L on cycle day 10 proved to be predictive of a P4 level of ≥ 30 nmol/L on either day 20 or day 25 with a sensitivity of 57% and a specificity of 89%. No other covariates, including the FSH level cycle day 5, LH levels during the follicular phase, age, weight, AFC and AMH cycle day 5 correlated with LP P4 levels. A significant correlation between FP E2 levels cycle day 5 (> 131pmol/L) and cycle day 10 (> 345pmol/L) and a LP P4 level ≥ 30 nmol/l was found; thus, the FP E2 level is a predictor of corpus luteum competence. Our findings highlight the existence of suboptimal P4 levels during the LP and a significant inter-individual and intra-cycle variation in P4 levels during the LP in regular menstruating women.","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"15 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141745673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nina Oufkir, Roman Rouzier, Xavier Paoletti, Claire Bonneau
{"title":"External validation of Standardized KELIM and platinum-resistant recurrence scores in patients with advanced epithelial ovarian cancer","authors":"Nina Oufkir, Roman Rouzier, Xavier Paoletti, Claire Bonneau","doi":"10.1186/s13048-024-01476-3","DOIUrl":"https://doi.org/10.1186/s13048-024-01476-3","url":null,"abstract":"Neoadjuvant chemotherapy followed by interval debulking surgery is currently a common treatment option for advanced epithelial ovarian cancer (EOC). The Standardized CA-125 ELIMination rate constant K (Std KELIM) and the Platinum Resistant Recurrence (PtRR) Score have been proposed as markers of tumor chemosensitivity. The aim of our study was to validate these tools for predicting platinum sensitivity in a real-world population of patients with advanced EOC treated with neoadjuvant chemotherapy. All patients with advanced EOC treated with neoadjuvant chemotherapy at the Institut Curie between 2000 and 2015 were included. The Std KELIM was calculated with the CA-125 concentrations during the first 100 days of chemotherapy. The predictive value of Std KELIM and PtRR scores for the risk of subsequent PtRR was assessed using receiver operating characteristic (ROC) curve analysis, logistic regression and calibration curve. Kaplan–Meier survival analysis was performed for the treatment-free interval from platinum (TFIp) therapy and overall survival (OS). Std KELIM data were available for 149 patients. The AUC was 0.67 for PtRR. A low Std KELIM was significantly associated with PtRR (OR = 0.19 (95% CI [0.06, 0.53], p = 0.002)) according to the univariate analysis. The calibration curve of the PtRR showed a slight but significant underestimation (p = 0.02) of the probability of platinum resistance. Favorable Std KELIM (≥ 1) alone and combined with the completeness of surgery were associated with significantly better survival in terms of TFIp and OS. Std KELIM is an early prognostic marker of chemosensitivity in a real-life setting complementary to surgical status. It could help the clinician in the early management of patients by identifying those with a worse prognosis.","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"61 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141737088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xuan Wang, Xiaoning Li, Li Wei, Yankun Yu, Yeernaer Hazaisihan, Lin Tao, Wei Jia
{"title":"Acetylation model predicts prognosis of patients and affects immune microenvironment infiltration in epithelial ovarian carcinoma.","authors":"Xuan Wang, Xiaoning Li, Li Wei, Yankun Yu, Yeernaer Hazaisihan, Lin Tao, Wei Jia","doi":"10.1186/s13048-024-01449-6","DOIUrl":"10.1186/s13048-024-01449-6","url":null,"abstract":"<p><strong>Background: </strong>Epithelial ovarian carcinoma (EOC) is a prevalent gynaecological malignancy. The prognosis of patients with EOC is related to acetylation modifications and immune responses in the tumour microenvironment (TME). However, the relationships between acetylation-related genes, patient prognosis, and the tumour immune microenvironment (TIME) are not yet understood. Our research aims to investigate the link between acetylation and the tumour microenvironment, with the goal of identifying new biomarkers for estimating survival of patients with EOC.</p><p><strong>Methods: </strong>Using data downloaded from the tumour genome atlas (TCGA), genotypic tissue expression (GTEx), and gene expression master table (GEO), we comprehensively evaluated acetylation-related genes in 375 ovarian cancer specimens and identified molecular subtypes using unsupervised clustering. The prognosis, TIME, stem cell index and functional concentration analysis were compared among the three groups. A risk model based on differential expression of acetylation-related genes was established through minimum absolute contraction and selection operator (LASSO) regression analysis, and the predictive validity of this feature was validated using GEO data sets. A nomogram is used to predict a patient's likelihood of survival. In addition, different EOC risk groups were evaluated for timing, tumour immune dysfunction and exclusion (TIDE) score, stemness index, somatic mutation, and drug sensitivity.</p><p><strong>Results: </strong>We used the mRNA levels of the differentially expressed genes related to acetylation to classify them into three distinct clusters. Patients with increased immune cell infiltration and lower stemness scores in cluster 2 (C2) exhibited poorer prognosis. Immunity and tumourigenesis-related pathways were highly abundant in cluster 3 (C3). We developed a prognostic model for ten differentially expressed acetylation-related genes. Kaplan-Meier analysis demonstrated significantly worse overall survival (OS) in high-risk patients. Furthermore, the TIME, tumour immune dysfunction and exclusion (TIDE) score, stemness index, tumour mutation burden (TMB), immunotherapy response, and drug sensitivity all showed significant correlations with the risk scores.</p><p><strong>Conclusions: </strong>Our study demonstrated a complex regulatory mechanism of acetylation in EOC. The assessment of acetylation patterns could provide new therapeutic strategies for EOC immunotherapy to improve the prognosis of patients.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"17 1","pages":"150"},"PeriodicalIF":3.8,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11264718/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141727317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tyler T Cooper, Dylan Z Dieters-Castator, Jiahui Liu, Gabrielle M Siegers, Desmond Pink, Lorena Veliz, John D Lewis, François Lagugné-Labarthet, Yangxin Fu, Helen Steed, Gilles A Lajoie, Lynne-Marie Postovit
{"title":"Targeted proteomics of plasma extracellular vesicles uncovers MUC1 as combinatorial biomarker for the early detection of high-grade serous ovarian cancer.","authors":"Tyler T Cooper, Dylan Z Dieters-Castator, Jiahui Liu, Gabrielle M Siegers, Desmond Pink, Lorena Veliz, John D Lewis, François Lagugné-Labarthet, Yangxin Fu, Helen Steed, Gilles A Lajoie, Lynne-Marie Postovit","doi":"10.1186/s13048-024-01471-8","DOIUrl":"10.1186/s13048-024-01471-8","url":null,"abstract":"<p><strong>Background: </strong>The five-year prognosis for patients with late-stage high-grade serous carcinoma (HGSC) remains dismal, underscoring the critical need for identifying early-stage biomarkers. This study explores the potential of extracellular vesicles (EVs) circulating in blood, which are believed to harbor proteomic cargo reflective of the HGSC microenvironment, as a source for biomarker discovery.</p><p><strong>Results: </strong>We conducted a comprehensive proteomic profiling of EVs isolated from blood plasma, ascites, and cell lines of patients, employing both data-dependent (DDA) and data-independent acquisition (DIA) methods to construct a spectral library tailored for targeted proteomics. Our investigation aimed at uncovering novel biomarkers for the early detection of HGSC by comparing the proteomic signatures of EVs from women with HGSC to those with benign gynecological conditions. The initial cohort, comprising 19 donors, utilized DDA proteomics for spectral library development. The subsequent cohort, involving 30 HGSC patients and 30 control subjects, employed DIA proteomics for a similar purpose. Support vector machine (SVM) classification was applied in both cohorts to identify combinatorial biomarkers with high specificity and sensitivity (ROC-AUC > 0.90). Notably, MUC1 emerged as a significant biomarker in both cohorts when used in combination with additional biomarkers. Validation through an ELISA assay on a subset of benign (n = 18), Stage I (n = 9), and stage II (n = 9) plasma samples corroborated the diagnostic utility of MUC1 in the early-stage detection of HGSC.</p><p><strong>Conclusions: </strong>This study highlights the value of EV-based proteomic analysis in the discovery of combinatorial biomarkers for early ovarian cancer detection.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"17 1","pages":"149"},"PeriodicalIF":3.8,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11253408/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141633713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}