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IL-2 transcriptomic patterns were evaluated using OmniSeq clinical-grade laboratory data and TCGA/UCSD cohorts, with expression normalized to a reference population and reported as percentiles. IL-2 tissue levels were assessed by ELISA in CRISPR-Cas9 GNAS-mutant Caco-2 models. High IL-2 expression associated with immune checkpoint and receptor signatures, correlated with GNAS alterations, and predicted improved overall survival.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/interleukin-2-transcriptomic-expression-correlates-with-prolonged-survival-and-with-gnas-alterations-in-patients-with-advanced-cancers/349319/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/interleukin-2-transcriptomic-expression-correlates-with-prolonged-survival-and-with-gnas-alterations-in-patients-with-advanced-cancers/349319.png","ImageObject",300,407,{"name":92,"@type":93},"Mimi","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-23","2026-09-22",true,{"@type":102,"interactionType":103,"userInteractionCount":8},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What was the main purpose of analyzing IL-2 transcriptomic expression?","Question",{"text":112,"@type":113},"To determine whether IL-2 RNA expression correlates with immune markers, gene alterations such as GNAS, and patient outcomes in advanced/metastatic cancers.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How were IL-2 transcript patterns and expression levels measured?",{"text":117,"@type":113},"IL-2 transcriptomic patterns were assessed using OmniSeq and UCSD/TCGA datasets, with UCSD data relativized to a reference population and expressed as percentiles. IL-2 levels were measured using ELISA in CRISPR-Cas9–engineered GNAS-mutant Caco-2 cell lines.",{"name":119,"@type":110,"acceptedAnswer":120},"What relationship did the study find between IL-2 expression, GNAS alterations, and survival?",{"text":121,"@type":113},"Higher IL-2 expression significantly correlated with immune checkpoint and related genomic aberrations and with a higher likelihood of GNAS alterations. IL-2 expression independently predicted better overall survival in both UCSD and TCGA cohorts.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},349319,1790196965,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":8,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145},2336477974920,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","ORIGINAL ARTICLE  \nInterleukin-2 transcriptomic expression correlates with prolonged survival and with GNAS alterations in patients with advanced cancers  \nJ. Ahmed1∗†‡, D. Nishizaki2†, Y. Fujiwara3, P. DePietro4, T. J. Jensen4, T. McFall5 ∗, S. Kato2† & R. Kurzrock6 , 7∗†  \n1Developmental Therapeutics Clinic, Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institute of Health, Bethesda; 2Center for Personalized Cancer Therapy and Division of Hematology and Oncology, Department of Medicine, University of California San Diego, Moores Cancer Center, La Jolla; 3Department of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo; 4OmniSeq Inc. (Labcorp), Buffalo; 5Department of Biochemistry and MCW Cancer Center, Medical College of Wisconsin, Milwaukee, USA; 6WIN Consortium, Paris, France; 7Division of Hematology-Oncology, Department of Medicine, MCW Cancer Center and Genomic Sciences and Precision Medicine Center, Medical College of Wisconsin, Milwaukee, Wisconsin, USA  \nAvailable online xxx  \nBackground: Interleukin-2 (IL-2) is a critical immunoregulatory molecule. IL-2 RNA expression and correlation with immune markers, gene alterations, and outcomes were analyzed in advanced/metastatic cancers.  \nPatients and methods: We investigated IL-2 transcript data through the OmniSeq clinical-grade laboratory [[https://](https://)[ ](https://)[www.omniseq.com/](www.omniseq.com/); University of California San Diego (UCSD) cohort] and The Cancer Genome Atlas (TCGA, [https://www.cancer.gov/tcga](https://www.cancer.gov/tcga)) databases. UCSD cohort transcriptomic patterns were relativized against a reference population (n = 735) and expressed as percentiles. IL-2 levels were measured by enzyme-linked immunosorbent assay in CRISPR-Cas9—engineered GNAS-mutant Caco-2 cell lines.  \nResults: Among 514 patients, 14.6% had high IL-2 RNA expression (≥75th percentile) and 35% had less than first percentile IL-2 expression. IL-2 expression (greater than or equal to first percentile RNA rank) significantly/ independently correlated with high expression of immune checkpoints (TIM-3, BTLA), IL-2Rγ subunits, and ERBB2, GNAS, and NF1 aberrations. Increasing IL-2 RNA expression (multivariable linear regression) correlated with increasing likelihood of GNAS alterations (P = 0.02) . GNASR201C-mutated (CRISPR) cell lines showed significantly higher levels of IL-2 than controls. IL-2 expression was an independent positive prognostic factor for overall survival (OS) [n = 489 UCSD patients with clinical data, hazard ratio (HR) 0.74, 95% confidence interval (CI) 0.57-0.96, P = 0.02, multivariable] and significantly correlated with longer OS in TCGA cohort (n = 9869, HR 0.84, 95% CI 0.79-0.91, P \u003C 0 .001) . Conclusions: High IL-2 tissue transcript levels correlated with better outcome in advanced cancer patients and those with GNAS alterations; the latter finding was confirmed by increased IL-2 production by CRISPR-edited GNASR201C cells, suggesting a functional interaction between this mutation and IL-2 .  \nKey words: immune checkpoint, interleukin 2, RNA expression  \n*Correspondence to: Dr Razelle Kurzrock, Division of Hematology-Oncology, Department of Medicine, MCW Cancer Center and Genomic Sciences and Precision Medicine Center, Medical College of Wisconsin, 8701 Watertown Plank Rd., Milwaukee, WI 53226, USA. Tel: +414-955-3447  \nE-mail: [rkurzrock@mcw.edu](rkurzrock@mcw.edu) (R. Kurzrock).  \nDr Jibran Ahmed, Developmental Therapeutics Clinic, Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institute of Health, 31 Center Drive, Bethesda, MD 20892, USA. Tel: +240-605-1927  \nE-mail: [jibran.ahmed@nih.gov](jibran.ahmed@nih.gov) (J. Ahmed).  \nDr Thomas McFall, Assistant Professor, Department of Biochemistry and MCW Cancer Center, Medical College of Wisconsin, 8701 Watertown Plank Rd., Milwaukee, WI 53226-0509, USA.  \nE-mail: [tmcfall@mcw.edu](tmcfall@mcw.edu) (T. McFall).  \n†These authors have ","cbCais8FOT3L00UV","https://ap.wps.com/l/cbCais8FOT3L00UV","pdf",2334081,14,"English","# Background\n# Patients and methods\n# Results\n# Conclusions\n# Introduction\n## Immune checkpoints and IL-2 regulation","[{\"question\":\"What was the main purpose of analyzing IL-2 transcriptomic expression?\",\"answer\":\"To determine whether IL-2 RNA expression correlates with immune markers, gene alterations such as GNAS, and patient outcomes in advanced/metastatic cancers.\"},{\"question\":\"How were IL-2 transcript patterns and expression levels measured?\",\"answer\":\"IL-2 transcriptomic patterns were assessed using OmniSeq and UCSD/TCGA datasets, with UCSD data relativized to a reference population and expressed as percentiles. IL-2 levels were measured using ELISA in CRISPR-Cas9–engineered GNAS-mutant Caco-2 cell lines.\"},{\"question\":\"What relationship did the study find between IL-2 expression, GNAS alterations, and survival?\",\"answer\":\"Higher IL-2 expression significantly correlated with immune checkpoint and related genomic aberrations and with a higher likelihood of GNAS alterations. IL-2 expression independently predicted better overall survival in both UCSD and TCGA cohorts.\"}]","Interleukin-2 transcriptomic expression correlates with prolonged survival and with GNAS alterations in patients with advanced cancers | PDF",1790082738,35]