Gynecologic oncology最新文献

{"title":"WRN dependency in dMMR/MSI-H endometrial cancer: Clinical perspectives of a novel synthetic lethality strategy","authors":"Giovanni Fucà , Cristian Dell'Acqua , Beatrice Peruffo , Gloria Lalli , Ilaria Sabatucci , Mariachiara Paderno , Giampaolo Di Martino , Mauro Signorelli , Matteo Maruccio , Fabio Martinelli , Domenica Lorusso","doi":"10.1016/j.ygyno.2025.02.021","DOIUrl":"10.1016/j.ygyno.2025.02.021","url":null,"abstract":"","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"195 ","pages":"Pages 12-15"},"PeriodicalIF":4.5,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143551534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Signal transduction pathway activity in adult-type granulosa cell tumor samples","authors":"G.J. Brink ,&nbsp;J.W. Groeneweg ,&nbsp;P. van der Ploeg ,&nbsp;G.N. Jonges ,&nbsp;E.H. Gort ,&nbsp;P.O. Witteveen ,&nbsp;R.P. Zweemer ,&nbsp;J.M.J. Piek","doi":"10.1016/j.ygyno.2025.02.018","DOIUrl":"10.1016/j.ygyno.2025.02.018","url":null,"abstract":"<div><h3>Objective</h3><div>This study aims to evaluate signal transduction pathway (STP) activity in adult-type granulosa cell tumors (aGCT) in order to identify potential therapeutic targets. These results are compared with STP activity in healthy ovarian tissue and low and high grade serous ovarian carcinoma (LGSC and HGSC).</div></div><div><h3>Methods</h3><div>STP activity was assessed by a RNA-based assay for the following oncogenic pathways: Hedhehog (HH), transforming growth factor beta (TGF-β), Notch, phosphoinositide 3-kinase (PI3K), mitogen-activated protein kinase (MAPK), androgen receptor (AR) and estrogen receptor (ER).</div></div><div><h3>Results</h3><div>Samples of 31 aGCTs and a healthy granulosa cell were included and compared with 24 LGSC and 50 HGSC samples. In aGCT, significantly higher activity of the HH, Notch, PI3K and ER pathways was found, as compared to healthy granulosa cells. When compared with LGSC and HGSC, aGCT exhibited significantly higher PI3K pathway activity and lower HH, TGF-β, Notch, MAPK, AR, and ER pathway activity.</div></div><div><h3>Conclusions</h3><div>Our results show high PI3K pathway activity in aGCT samples. Pathway activity contrasts with findings in both healthy granulosa cells and serous ovarian carcinoma. Therefore, the PI3K pathway may be a target for treatment, specifically for aGCT patients.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"195 ","pages":"Pages 6-11"},"PeriodicalIF":4.5,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143529831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sentinel lymph node biopsy at the time of hysterectomy for early-stage cervical cancer: A cost-effectiveness analysis","authors":"A.R. Walker ,&nbsp;S. Leite ,&nbsp;Y.S. Chen ,&nbsp;S.P. Huepenbecker ,&nbsp;A. Graul","doi":"10.1016/j.ygyno.2025.02.019","DOIUrl":"10.1016/j.ygyno.2025.02.019","url":null,"abstract":"<div><h3>Objective</h3><div>Standard management of early-stage cervical cancer is hysterectomy with bilateral pelvic lymph node evaluation. Based on the final results of the prospective international SENTIX Trial, we sought to determine the cost-effectiveness (CE) of type of lymph node assessment for early-stage cervical cancer.</div></div><div><h3>Methods</h3><div>A decision analytic model was created using TreeAgePro 2023 software to evaluate the strategies of routine full lymph node dissection (LND) without para-aortic node dissection verses sentinel lymph node dissection (SNLD) at the time of hysterectomy. It was assumed that patients in the SLND group underwent unilateral or bilateral full LND in the event of unilateral or bilateral non-mapping, respectively. Outcomes included cost, quality adjusted life years (QALYs), perioperative complications, lymphedema, and recurrence 24 months after surgery. Univariate and probabilistic sensitivity analyses investigated the impact of the strategies.</div></div><div><h3>Results</h3><div>In a theoretical cohort of 1000 women, SLND was the dominate strategy resulting in 1804 QALYs, cost $28.54 M, and incremental cost-effectiveness ratio (ICER) -$83,693, compared to routine LND. This strategy resulted in 53 total peri-operative complications and a 77 % reduction in lymphedema cases. At 24 months, the recurrence rate was 62 in the SLND group and 89 in the full LND group, respectively.</div></div><div><h3>Conclusions</h3><div>Compared to routine full LND, SLND is CE with a reduction in post-operative complications and lymphedema with an ICER of -$83,693. When feasible, this surgical technique should be considered at the time of hysterectomy.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"195 ","pages":"Pages 1-5"},"PeriodicalIF":4.5,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143511168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bevacizumab beyond progression: Impact of subsequent bevacizumab re-treatment in patients with ovarian, fallopian tube, and peritoneal cancer after progression","authors":"Amma Asare ,&nbsp;Rebecca Ann Previs ,&nbsp;Daniel Spinosa ,&nbsp;Bryan Fellman ,&nbsp;Amelia L. Scott ,&nbsp;Isabelle Mulder ,&nbsp;May Mahmoud ,&nbsp;Ahmed Enbaya ,&nbsp;Jean Hansen Siedel ,&nbsp;Lauren Cobb ,&nbsp;Pamela T. Soliman ,&nbsp;Anil K. Sood ,&nbsp;Robert L. Coleman ,&nbsp;Angeles Alvarez Secord ,&nbsp;Shannon N. Westin","doi":"10.1016/j.ygyno.2025.02.015","DOIUrl":"10.1016/j.ygyno.2025.02.015","url":null,"abstract":"<div><h3>Background</h3><div>This study evaluated whether patients with epithelial ovarian, fallopian tube, and primary peritoneal carcinoma (OC) who are immediately re-treated with bevacizumab derive benefit after disease progression on a bevacizumab-containing regimen.</div></div><div><h3>Methods</h3><div>This multi-institutional, retrospective study compared patients with high grade non-mucinous epithelial OC who received bevacizumab followed directly by another bevacizumab-containing treatment regimen to patients who received bevacizumab followed by a regimen that did not contain bevacizumab (or received no further treatment). Progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan Meier product-limit estimator and modeled via Cox proportional hazards regression.</div></div><div><h3>Results</h3><div>Among 226 patients with OC who received bevacizumab as part of a treatment regimen,103 received sequential treatment with bevacizumab and 123 received a bevacizumab-containing regimen followed by a non-bevacizumab-containing regimen at the time of progression. Median follow-up for all subjects was 17.3 months (range, 1.2–138.2 months). Median PFS was 17.2 months (95 % CI, 14.3–21.2) for patients who received sequential bevacizumab re-treatment and 5.1 months (95 % CI, 4.3–6.3) for patients who received bevacizumab without bevacizumab-containing re-treatment (<em>p</em> &lt; 0.001). Median OS was 29.9 months (95 % CI, 26.1–35.4) for patients who received sequential bevacizumab re-treatment (<em>p</em> &lt; 0.001) and 12.4 months (95 % CI, 9.2–16.7) for patients who did not receive bevacizumab-containing re-treatment.</div></div><div><h3>Conclusion</h3><div>Patients with OC treated with bevacizumab-containing regimens sequentially at the time of progression have prolonged survival compared to patients who received no re-treatment with bevacizumab.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"194 ","pages":"Pages 112-118"},"PeriodicalIF":4.5,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143471318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ultrasound-based versus immediate biopsy-based management of postmenopausal bleeding in non-Hispanic Black and non-Hispanic White individuals","authors":"Angela C. Nolin ,&nbsp;Sage L. Atkins ,&nbsp;Evan R. Myers ,&nbsp;Nicolas Wentzensen ,&nbsp;Megan A. Clarke ,&nbsp;Stephanie V. Blank ,&nbsp;Jason D. Wright ,&nbsp;Kemi M. Doll ,&nbsp;Laura J. Havrilesky","doi":"10.1016/j.ygyno.2025.02.006","DOIUrl":"10.1016/j.ygyno.2025.02.006","url":null,"abstract":"<div><h3>Background</h3><div>Ultrasound-based evaluation of endometrial thickness to rule out endometrial cancer in patients with postmenopausal bleeding (PMB) is not sufficiently validated in the non-Hispanic Black (NHB) population. Differences in ultrasound performance between NHB and non-Hispanic White (NHW) patients may contribute to documented disparities in cancer-associated survival.</div></div><div><h3>Methods</h3><div>We developed a decision-tree model, informed by literature and institutional data, comparing an immediate biopsy-based strategy (BBS) to an ultrasound-based strategy (UBS) to evaluate PMB in NHB and NHW patients. Primary outcomes were the probability of a missed cancer diagnosis and incremental biopsies per additional cancer detected. Fibroid prevalence, endometrial visibility, and race were modeled using institutional patient-level data. Prompt endometrial sampling following abnormal ultrasound (perfect follow-up) was assumed; institutionally observed follow-up rates were alternatively modeled.</div></div><div><h3>Results</h3><div>In a simulated cohort of 10,000 patients with PMB, UBS missed 109 (95 % prediction interval (PI) 85–159) cancer diagnoses compared to 70 missed for BBS. Compared to UBS, BBS resulted in 123 (95 % PI 45–265) biopsies/additional cancer detected for NHB and 155 (95 % PI 47–398) for NHW. Under observed follow-up rates, BBS resulted in 33 (95 % PI 26–38) biopsies/additional cancer detected for NHB and 44 (95 % PI 30–54) for NHW. NHB derived higher value (fewer biopsies/additional cancer detected) from BBS than NHW, particularly with fibroids present.</div></div><div><h3>Conclusion</h3><div>BBS has higher value compared to UBS under observed/imperfect levels of follow-up and enhanced value when fibroids are present and among NHB patients. These results suggest that endometrial sampling should be offered at time of initial evaluation for PMB.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"194 ","pages":"Pages 105-111"},"PeriodicalIF":4.5,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143454500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Platinum-free interval and response to platinum retreatment or lenvatinib/pembrolizumab in patients with recurrent endometrial cancer: A real-world endometrial cancer molecularly targeted therapy consortium cohort study","authors":"Paulina J. Haight ,&nbsp;Marilyn Sanchez ,&nbsp;Samantha M. Thomas ,&nbsp;Carson Smitherman ,&nbsp;Casey Cosgrove ,&nbsp;Victoria Bae-Jump ,&nbsp;Sarah Crafton ,&nbsp;Kari Hacker ,&nbsp;Emily Ko ,&nbsp;Thomas Krivak ,&nbsp;Olivia Lara ,&nbsp;Kathleen Moore ,&nbsp;Mary M. Mullen ,&nbsp;Bhavana Pothuri ,&nbsp;Premal H. Thaker ,&nbsp;Christina Washington ,&nbsp;Rebecca Arend ,&nbsp;Bradley Corr ,&nbsp;Linda Duska ,&nbsp;Amanda Jackson ,&nbsp;Floor Backes","doi":"10.1016/j.ygyno.2025.02.013","DOIUrl":"10.1016/j.ygyno.2025.02.013","url":null,"abstract":"<div><h3>Objective</h3><div>We sought to determine the association between platinum-free interval (PFI) and response to retreatment with platinum-based chemotherapy vs lenvatinib/pembrolizumab in patients with recurrent endometrial cancer.</div></div><div><h3>Methods</h3><div>Endometrial Cancer Molecularly Targeted Therapy (ECMT2) Consortium patients with recurrent disease were included in this retrospective analysis if they received first-line treatment with platinum-based chemotherapy (adjuvant or first recurrence), followed by second-line re-treatment with platinum or lenvatinib/pembrolizumab. PFI was defined as time between date of last platinum to start date of second-line therapy. Patients were stratified according to PFI ≤12 months or &gt; 12 months. Overall response rate (ORR) to second-line treatment was estimated after stratification by PFI.</div></div><div><h3>Results</h3><div>Of 217 patients, 146 (67 %) underwent retreatment with platinum and 71 (33 %) were treated with lenvatinib/pembrolizumab. 127 (59 %) had PFI ≤12 months, and 84 (39 %) patients had PFI &gt;12 months. Patients treated with platinum had longer PFI than those treated with lenvatinib/pembrolizumab (median PFI 12.9 vs 4.6 months; <em>p</em> &lt; 0.001). ORR was 58 % vs 49 % for platinum vs lenvatinib/pembrolizumab (<em>p</em> = 0.27). For all patients, ORR was 68 % vs 47 % with PFI &gt;12 months and ≤ 12 months, respectively (<em>p</em> = 0.002). At each PFI, ORR was similar regardless of treatment with platinum or lenvatinib/pembrolizumab (PFI ≤12 months ORR 49 % vs 44 % respectively, <em>p</em> = 0.75; PFI &gt;12 months ORR 67 % vs 75 % respectively, <em>p</em> = 0.74).</div></div><div><h3>Conclusion</h3><div>Longer PFI is associated with improved response to second-line treatment in patients with recurrent endometrial cancer. Despite utilization of PFI for real-world treatment decisions, it was not found to predict response between regimens at any given PFI.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"194 ","pages":"Pages 98-104"},"PeriodicalIF":4.5,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143454499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predicting lymph node metastases in three different vulvar squamous cell carcinoma subgroups","authors":"Anne F. van Velzen ,&nbsp;Adam J. Tulling ,&nbsp;Mariëtte I.E. van Poelgeest ,&nbsp;Tjalling Bosse ,&nbsp;Helena C. van Doorn ,&nbsp;Kim E. Kortekaas ,&nbsp;Linda S. Nooij","doi":"10.1016/j.ygyno.2025.02.008","DOIUrl":"10.1016/j.ygyno.2025.02.008","url":null,"abstract":"<div><h3>Objective</h3><div>This study aimed to analyze the risk of lymph node metastases (LNM) in three different VSCC subgroups (HPV-positive (HPVpos), HPV-negative p53 wildtype (HPVneg/p53wt) and HPV-negative p53 abnormal (HPVneg/p53abn)), and develop a predictive model for clinical use.</div></div><div><h3>Methods</h3><div>A retrospective cohort study was performed, collecting data from all surgically treated VSCC patients between 2000 and 2022 from two oncology clinics. The primary outcome was the risk of groin LNM at diagnosis. Prognostic variables for LNM were identified using uni- and multivariate analyses. A model was created to estimate the probability of LNM at diagnosis.</div></div><div><h3>Results</h3><div>A total of 516 patients were included, of which 94 (18.2 %) were HPVpos, 117 (22.7 %) HPVneg/p53wt, and 305 (59.1 %) HPVneg/p53abn. LNM rates were 17.0 %, 26.5 %, and 35.1 %, respectively (<em>p</em> = .002). Molecular subgroup remained a significant predictor of LNM after adjusting for age, tumor size, and depth of invasion (<em>p</em> = .028). A model using these variables was developed to predict LNM at diagnosis.</div></div><div><h3>Conclusion</h3><div>HPVneg/p53abn VSCCs have a higher risk of LNM compared to HPVpos VSCCs. HPVneg/p53wt VSCC are considered an intermediate risk group. Molecular subgroups contribute to LNM risk assessment at diagnosis. We developed a well-performing, clinically feasible model to predict the risk of LNM at diagnosis.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"194 ","pages":"Pages 86-90"},"PeriodicalIF":4.5,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143446049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of induction chemotherapy during the COVID-19 pandemic for treatment of locally advanced cervical cancer in Botswana","authors":"Emily MacDuffie ,&nbsp;Caroline Kernell ,&nbsp;Jessica George ,&nbsp;Memory Bvochora-Nsingo ,&nbsp;Peter Vuylsteke ,&nbsp;Lisa Bazzett-Matabele ,&nbsp;Kgosi Hughes ,&nbsp;Megan Kassick ,&nbsp;Surbhi Grover","doi":"10.1016/j.ygyno.2025.02.002","DOIUrl":"10.1016/j.ygyno.2025.02.002","url":null,"abstract":"<div><h3>Objectives</h3><div>Standard chemoradiation (CRT) treatment for cervical cancer was disrupted in Botswana during the COVID-19 pandemic. Patients were prescribed induction chemotherapy (IC) to bridge delays to radiotherapy (RT) or CRT (IC + RT/CRT).</div></div><div><h3>Methods</h3><div>This prospective observational study compared outcomes of locally advanced cervical cancer patients who received IC + RT/CRT (<em>n</em> = 67) between 2019 and 2022 to historical controls who received CRT (<em>n</em> = 169) between 2014 and 2019. IC + RT/CRT consisted of four cycles of paclitaxel 175 mg/m² and carboplatin (area under the curve 5–6) prescribed once every three weeks followed by external beam RT and high-dose-rate brachytherapy with or without weekly concurrent cisplatin. Two-year overall survival (OS) was estimated using the Kaplan-Meier method; univariable and multivariable analyses (MVA) were conducted using Cox proportional hazards regression.</div></div><div><h3>Results</h3><div>Median follow-up was 28.9 months (95 % CI 27.4–32.7 months). Two-year OS of the IC + RT/CRT cohort (80.2 % [95 % CI: 69.8–92.1 %]) did not differ from the historical CRT cohort (77.5 % [95 % CI 71.3–84.1 %]). Improved OS was associated with receiving ≥3 cycles of IC on MVA. Secondary analysis among those prescribed IC + RT/CRT (<em>n</em> = 91) demonstrated no difference in 2-year OS (66.8 % [95 % CI: 56.9–78.3 %]) compared to CRT historical controls. Receipt of the prescribed IC + RT/CRT was associated with increased OS on MVA.</div></div><div><h3>Conclusions</h3><div>Survival of patients who received IC + RT/CRT did not differ from historical CRT controls and was associated with ≥3 cycles of IC, suggesting that IC may be a feasible treatment pathway when RT is delayed.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"194 ","pages":"Pages 91-97"},"PeriodicalIF":4.5,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143454498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the differences between BRCA mutated and HRwild-type high grade serous ovarian cancer: A multiomic analysis","authors":"Ayesha B. Alvero ,&nbsp;Sharon Wu ,&nbsp;Alex Farrell ,&nbsp;Seongho Kim ,&nbsp;John J. Wallbillich ,&nbsp;Ira Winer ,&nbsp;Robert Morris ,&nbsp;David Spetzler ,&nbsp;Matthew L. Anderson ,&nbsp;Alberto Puccini ,&nbsp;Nathaniel L. Jones ,&nbsp;Thomas J. Herzog ,&nbsp;Premal H. Thaker ,&nbsp;Gil Mor ,&nbsp;Radhika P. Gogoi","doi":"10.1016/j.ygyno.2025.02.010","DOIUrl":"10.1016/j.ygyno.2025.02.010","url":null,"abstract":"<div><h3>Objective</h3><div>The purpose of this study was to evaluate the transcriptomic profile of BRCA1 mutant (BRCA1mut) and BRCA2 mutant (BRCA2mut) HGSOC compared to homologous recombination wild-type (HRwt) tumors utilizing the CARIS database.</div></div><div><h3>Methods</h3><div>Next-generation and Whole Transcriptome Sequencing (WTS; Caris Life Sciences, Phoenix, AZ) was performed on a total of 2745 HGSOC tumor samples. BRCA mutations were defined as variants resulting in loss-of-function of the protein and HRwt was defined as samples wildtype for aberrations in both BRCA1 and BRCA2, as well as for 28 other HR genes. HRwt group was further classified into HRwt/LOH-low (&lt;16 %) and HRwt/LOH-high (≥16 %). Genomic analysis consists of mutation analysis and measurements of TMB and MSI. Transcriptomic analysis included identification of Differentially expressed genes (DEGs), GSEA and immune deconvolution.</div></div><div><h3>Results</h3><div>We identified 519 (19 %) BRCA1-mut, 302 (11 %) BRCA2-mut, and 739 (27 %) HRwt/LOH high and 1181 (43 %) HRwt/LOH low HGSOC. <em>TP53</em> was the most commonly mutated gene in all groups. Mutations in <em>PIK3CA</em> were most common in HRwt/LOH-low compared to BRCA1-mut and BRCA2-mut HGSOC. TMB-H was highest in BRCA2-mut compared to BRCA1-mut, HRwt/LOH high and HRwt/LOH low tumors. In contrast, higher NKT cell infiltration, higher T cell inflamed and IFNγ scores, and higher PDL1 expression were observed in BRCA1-mut tumors.</div></div><div><h3>Conclusion</h3><div>Our findings emphasize the differential immune profiles based on BRCA1 and BRCA2 mutations and suggest potential therapeutic targets, including treatment strategies that incorporate immunotherapy and target specific genomic alterations.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"194 ","pages":"Pages 71-79"},"PeriodicalIF":4.5,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143437362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exosome transmit the ability of migration and invasion in heterogeneous ovarian cancer cells by regulating autophagy via targeting hsa-miR-328","authors":"Hengzi Sun ,&nbsp;Xiao Huo ,&nbsp;Xiaoning Bi ,&nbsp;Dongyan Cao ,&nbsp;Jiaxin Yang ,&nbsp;Keng Shen ,&nbsp;Peng Peng","doi":"10.1016/j.ygyno.2025.02.011","DOIUrl":"10.1016/j.ygyno.2025.02.011","url":null,"abstract":"<div><h3>Purpose</h3><div>This study investigates the role of exosomes in ovarian cancer heterogeneity, which contributes to metastasis. By examining the variability of exosomes from different ovarian cancer cells, which aims to elucidate the molecular mechanisms driving this heterogeneity.</div></div><div><h3>Experimental design</h3><div>Ovarian cancer cell lines were subjected to clonal culture and single-cell sorting. Monoclonal cell lines with different migration and invasion capabilities were identified using Transwell assays. The effect of exosomes on these abilities was assessed through Transwell, scratch tests, and in vivo experiments. High-throughput sequencing was used to compare miRNAs in exosomes with mRNAs in cells. Techniques like electron microscopy, immunofluorescence, adenoviral transduction, western blot, RNA-binding protein immunoprecipitation, and fluorescence in situ hybridization were employed to explore how exosomes affect cell migration and invasion.</div></div><div><h3>Results</h3><div>Two subpopulations, SK-H/A-H (highly invasive) and SK-L/A-L (less invasive), were isolated. Exosomes from SK-H and A-H cells enhanced the migration and invasion of SK-L and A-L cells. Hsa-miR-328-3p was significantly upregulated in exosomes from SK-H and A-H cells, promoting invasive traits in SK-L and A-L cells, reducing Raf1 and mTOR expression, and increasing ULK1 and LC3B levels to promote autophagy. Overexpression of pri-miR-328-3p in SK-L and A-L cells resulted in similar effects.</div></div><div><h3>Conclusions</h3><div>Ovarian cancer cells with different invasive capabilities secrete distinct exosomes. Exosomes from highly invasive cells enhance these traits in less aggressive cells via hsa-miR-328-3p, which targets Raf1, disrupts the mTOR pathway, and promotes autophagy. This study highlights exosomes as carriers of hsa-miR-328-3p, mediating intercellular communication and autophagy to influence ovarian cancer cell heterogeneity.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"194 ","pages":"Pages 60-70"},"PeriodicalIF":4.5,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143428740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}