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Integrative deconvolution across multiple algorithms was externally validated on independent datasets.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/comparative-tumor-microenvironment-analysis-of-primary-and-recurrent-ovarian-granulosa-cell-tumors/381077/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/comparative-tumor-microenvironment-analysis-of-primary-and-recurrent-ovarian-granulosa-cell-tumors/381077.png","ImageObject",300,407,{"name":42,"@type":43},"Liam","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-30","2026-09-24",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",9,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What is the main goal of this study?","Question",{"text":63,"@type":64},"To characterize the tumor microenvironment of primary and recurrent adult-type granulosa cell tumors and identify correlates of disease recurrence.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How were gene expression differences analyzed?",{"text":68,"@type":64},"Total RNA sequencing was performed on primary and recurrent tumor samples, then DESeq2 identified differentially expressed genes. Functional enrichment and gene set enrichment analyses were conducted using clusterProfiler and GSVA.",{"name":70,"@type":61,"acceptedAnswer":71},"What tumor microenvironment changes were observed in recurrent tumors?",{"text":72,"@type":64},"Integrative tumor microenvironment analysis showed statistically significant depletion of cancer-associated fibroblasts in recurrent tumors, confirmed across multiple independent datasets.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},381077,1790792991,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,110,115,119,122,126],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":85,"show_sort_weight":86,"slug":87},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":89,"show_sort_weight":90,"slug":91},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":93,"show_sort_weight":94,"slug":95},"Exam",70,"exam",{"id":97,"doc_module":4,"doc_module_name":25,"category_name":98,"show_sort_weight":99,"slug":100},5,"Comic",60,"comic",{"id":102,"doc_module":4,"doc_module_name":25,"category_name":103,"show_sort_weight":104,"slug":105},6,"Technology",50,"technology",{"id":107,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":108,"slug":109},7,40,"healthcare",{"id":111,"doc_module":4,"doc_module_name":25,"category_name":112,"show_sort_weight":113,"slug":114},8,"Research & Report",30,"research-report",{"id":55,"doc_module":4,"doc_module_name":25,"category_name":116,"show_sort_weight":117,"slug":118},"Religion & Spirituality",20,"religion-spirituality",{"id":117,"doc_module":4,"doc_module_name":25,"category_name":120,"show_sort_weight":117,"slug":121},"World Cup","world-cup",{"id":123,"doc_module":4,"doc_module_name":25,"category_name":124,"show_sort_weight":123,"slug":125},10,"Lifestyle","lifestyle",{"id":127,"doc_module":4,"doc_module_name":25,"category_name":128,"show_sort_weight":97,"slug":129},19,"General","general",{"code":4,"msg":82,"data":131},{"doc_id":79,"user_id":132,"nickname":42,"user_avatar":133,"doc_module":4,"category_id":107,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":139,"language":140,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":12,"update_tm":144,"read_time":113},8796095461564,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","Comparative Tumor Microenvironment Analysis of Primary and Recurrent Ovarian Granulosa Cell Tumors Eleonora Khlebus1, Veena K. Vuttaradhi1, Thomas Welte1, Namrata Khurana1, Joseph Celestino2, Hannah C. Beird1, Curtis Gumbs1, Latasha Little1, Alejandra Flores Legarreta2, Bryan M. Fellman3, Tri Nguyen2, Barrett Lawson4, Sammy Ferri-Borgogno2, Samuel C. Mok2, Russell R. Broaddus5, David M. Gershenson2, P. Andrew Futreal1, and R. Tyler Hillman1,2,6  \n◥  \nAdult-type granulosa cell tumors (aGCT) are rare ovarian sex cord tumors with few effective treatments for recurrent disease. The objective of this study was to characterize the tumor microenvironment (TME) of primary and recurrent aGCTs and to identify correlates of disease recurrence. Total RNA sequencing (RNA-seq) was performed on 24 pathologically confirmed, cryopreserved aGCT samples, including 8 primary and 16 recurrent tumors. After read alignment and quality-control filtering, DESeq2 was used to identify differentially expressed genes (DEG) between primary andrecurrent tumors. Functional enrichment pathway analysis and gene set enrichment analysis was performed using “clusterProfiler”and “GSVA” R packages. TME composition was investigated through the analysis and integration of multiple published RNAseq deconvolution algorithms. TME analysis results were externally validated using data from independent previously published RNA-  \nseq datasets. A total of 31 DEGs were identified between primary andrecurrent aGCTs. These included genes with known function in hormone signaling such as LHCGR and INSL3 (more abundant in primary tumors) and CYP19A1 (more abundant in recurrent tumors) . Gene set enrichment analysis revealed that primarily immune-related and hormone-regulated gene sets expression was increased in recurrent tumors. Integrative TME analysis demonstrated statistically significant depletion of cancer-associated fibroblasts in recurrent tumors. This finding was confirmed in multiple independent datasets.  \nImplications: Recurrent aGCTs exhibit alterations in hormone pathway gene expression as well as decreased infiltration of cancer-associated fibroblasts, suggesting dual roles for hormonal signaling and TME remodeling underpinning disease relapse.  \nIntroduction  \nAdult-type granulosa cell tumors (aGCT) are rare malignant ovarian sex cord-stromal tumors that exhibit frequent FOXL2 c.C402G (p. Cys134Trp) hotspot mutations (1, 2) . Most primary aGCTs are diagnosed at an early stage and can be removed surgically with long-term survival rates exceeding 90%(3) . Importantly, aGCT recurrence is difficult to predict and is nearly always incurable after relapse. Treatment of relapsed aGCTs remains a significant clinical challenge. Although knowledge about tumor-intrinsic correlates of recurrence is  \n1Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas. 2Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas. 3Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas. 4Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas. 5Department of Pathology and Laboratory Medicine, The University of North Carolina, Chapel Hill, North Carolina. 6CPRIT Scholar in Cancer Research, Houston, Texas.  \nPrior Presentation: This work was presented in part as a poster at the MD Anderson Cancer Center 2022 Leading Edge of Cancer Research Symposium (November 17–18, 2022) .  \nCorresponding Author: R. Tyler Hillman, The University of Texas MD Anderson Cancer Center, 1155 Pressler Street, Unit 1362, Houston, TX 77030 . Phone: 281-  \n658-2887; E-mail: [rthillman@mdanderson.org](rthillman@mdanderson.org)  \n[Mol Cancer Res 2023](Mol Cancer Res 2023);[21:483](21:483)–[94](94)  \n[doi:](doi: 10.1158/1541-7786.MCR-22-0623)[ 10.1158/1541-7786.MCR-22-0623](doi: 10.1158/1541-7786.MCR-22-0623)  \nThis open access article is distribute","cbCaimU0vNqoj0Co","https://ap.wps.com/l/cbCaimU0vNqoj0Co","pdf",4494843,12,"English","# Introduction\n## Adult-type granulosa cell tumors and recurrence\n## Prior genetic and transcriptomic studies","[{\"question\":\"What is the main goal of this study?\",\"answer\":\"To characterize the tumor microenvironment of primary and recurrent adult-type granulosa cell tumors and identify correlates of disease recurrence.\"},{\"question\":\"How were gene expression differences analyzed?\",\"answer\":\"Total RNA sequencing was performed on primary and recurrent tumor samples, then DESeq2 identified differentially expressed genes. Functional enrichment and gene set enrichment analyses were conducted using clusterProfiler and GSVA.\"},{\"question\":\"What tumor microenvironment changes were observed in recurrent tumors?\",\"answer\":\"Integrative tumor microenvironment analysis showed statistically significant depletion of cancer-associated fibroblasts in recurrent tumors, confirmed across multiple independent datasets.\"}]","Comparative Tumor Microenvironment Analysis of Primary and Recurrent Ovarian Granulosa Cell Tumors | PDF",1790243475]