Differential role of glucocorticoid receptor based on its cell type specific expression on tumor cells and infiltrating lymphocytes

Differential role of glucocorticoid receptor based on its cell type specific expression on tumor cells and infiltrating lymphocytes | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Differential role of glucocorticoid receptor based on its cell type specific expression on tumor cells and infiltrating lymphocytes Snijesh V P, Vidya P. Nimbalkar, Sharada Patil, Savitha Rajarajan, and 8 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3829052/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background : The glucocorticoid receptor (GR) is frequently expressed in breast cancer (BC), and its prognostic implications are contingent on estrogen receptor (ER) status. To address conflicting reports and explore therapeutic potential, a GR signature (GRsig) independent of ER status was developed. We also investigated cell type-specific GR protein expression in BC tumor epithelial cells and infiltrating lymphocytes. Methods : GRsig was derived from Dexamethasone-treated cell lines through a bioinformatic pipeline. Immunohistochemistry assessed GR protein expression. Associations between GRsig and tumor phenotypes (proliferation, cytolytic activity (CYT), immune cell distribution, and epithelial-to-mesenchymal transition(EMT)) were explored in public datasets. Single-cell RNA sequencing data evaluated context-dependent GR roles, and a cell type-specific prognostic role was assessed in an independent BC cohort. Results : High GRsig levels were associated with a favorable prognosis across BC subtypes. Tumor-specific high GRsig correlated with lower proliferation, increased CYT, and anti-tumorigenic immune cells. Single-cell data analysis revealed higher GRsig expression in immune cells, negatively correlating with EMT while a positive correlation was observed with EMT primarily in tumor and stromal cells. Univariate and multivariate analyses demonstrated the robust and independent predictive capability of GRsig for favorable prognosis. GR protein expression on immune cells in triple-negative tumors indicated a favorable prognosis. Conclusion : This study underscores the cell type-specific role of GR, where its expression on tumor cells is associated with aggressive features like EMT, while in infiltrating lymphocytes, it predicts a better prognosis, particularly within TNBC tumors. The GRsig emerges as a promising independent prognostic indicator across diverse BC subtypes. Cancer Biology Bioinformatics Translational Medicine Oncology Glucocorticoid receptor Gene signature Proliferation Tumor microenvironment Epithelial to mesenchymal transition Prognosis Full Text Additional Declarations The authors declare no competing interests. Supplementary Figures and Tables are not available with this version. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3829052","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":264719975,"identity":"2449e566-2511-4e01-8205-e4fd6f37150b","order_by":0,"name":"Snijesh V P","email":"","orcid":"https://orcid.org/0000-0002-2215-9042","institution":"Division of Molecular Medicine, St. John’s Medical College, St. John’s Research Institute, Bangalore, Karnataka, India","correspondingAuthor":false,"prefix":"","firstName":"Snijesh","middleName":"V","lastName":"P","suffix":""},{"id":264719976,"identity":"b53f4cc3-82fa-4857-9912-dedc27236ea3","order_by":1,"name":"Vidya P. 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To address conflicting reports and explore therapeutic potential, a GR signature (GRsig) independent of ER status was developed. We also investigated cell type-specific GR protein expression in BC tumor epithelial cells and infiltrating lymphocytes.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e: GRsig was derived from Dexamethasone-treated cell lines through a bioinformatic pipeline. Immunohistochemistry assessed GR protein expression. Associations between GRsig and tumor phenotypes (proliferation, cytolytic activity (CYT), immune cell distribution, and epithelial-to-mesenchymal transition(EMT)) were explored in public datasets. Single-cell RNA sequencing data evaluated context-dependent GR roles, and a cell type-specific prognostic role was assessed in an independent BC cohort.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e: High GRsig levels were associated with a favorable prognosis across BC subtypes. Tumor-specific high GRsig correlated with lower proliferation, increased CYT, and anti-tumorigenic immune cells. Single-cell data analysis revealed higher GRsig expression in immune cells, negatively correlating with EMT while a positive correlation was observed with EMT primarily in tumor and stromal cells. Univariate and multivariate analyses demonstrated the robust and independent predictive capability of GRsig for favorable prognosis. GR protein expression on immune cells in triple-negative tumors indicated a favorable prognosis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e: This study underscores the cell type-specific role of GR, where its expression on tumor cells is associated with aggressive features like EMT, while in infiltrating lymphocytes, it predicts a better prognosis, particularly within TNBC tumors. The GRsig emerges as a promising independent prognostic indicator across diverse BC subtypes.\u003c/p\u003e","manuscriptTitle":"Differential role of glucocorticoid receptor based on its cell type specific expression on tumor cells and infiltrating lymphocytes","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-01-03 15:04:46","doi":"10.21203/rs.3.rs-3829052/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"b4dc7f35-cfbd-4210-9337-8b1c13faeb95","owner":[],"postedDate":"January 3rd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":27891950,"name":"Cancer Biology"},{"id":27891951,"name":"Bioinformatics"},{"id":27891952,"name":"Translational Medicine"},{"id":27891953,"name":"Oncology"}],"tags":[],"updatedAt":"2024-01-03T15:04:46+00:00","versionOfRecord":[],"versionCreatedAt":"2024-01-03 15:04:46","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3829052","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3829052","identity":"rs-3829052","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}