Structural Dynamics of Microtubules in Glioma: Impact on Macrophage M2 Polarization and Tumor Cell Heterogeneity

Structural Dynamics of Microtubules in Glioma: Impact on Macrophage M2 Polarization and Tumor Cell Heterogeneity | 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 Structural Dynamics of Microtubules in Glioma: Impact on Macrophage M2 Polarization and Tumor Cell Heterogeneity Xinyu Liu, Xin Sun, Ningning Yao, Shi Hua, Yucheng Lu This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7855246/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 28 Feb, 2026 Read the published version in Journal of Translational Medicine → Version 1 posted 4 You are reading this latest preprint version Abstract Background: Glioma is the most common malignant brain tumor, characterized by high heterogeneity and poor prognosis. Microtubule dynamics regulate tumor progression and immune escape; however, the prognostic significance of microtubule-associated genes in glioma and their immunological significance still lack systematic investigation. Methods: We integrated transcriptomic and clinical data from TCGA and CGGA cohorts to identify microtubule-associated genes with prognostic significance. A risk score (RS) model was established using Cox regression and validated in independent cohorts. Spatial transcriptomics and single-cell RNA sequencing were applied to characterize the expression patterns of candidate genes across glioma microregions and immune cell populations. Functional enrichment analysis, immune infiltration assessment, and drug sensitivity profiling were performed to explore the biological mechanisms and clinical implications of the RS model. Results: We identified 18 microtubule-associated genes that are significantly associated with glioma prognosis and constructed a four-gene RS model, which robustly predicts overall survival. Tumors with high-RS exhibited increased infiltration of M2 macrophages, enhanced immunosuppressive signaling, and reduced sensitivity to alkylating agents. Spatial and single-cell analyses confirmed that core RS genes are enriched at the tumor-immune interface and shaped macrophage polarization dynamics. Conclusion: Our findings highlight microtubule-associated genes as key regulators of the glioma immune microenvironment. The RS model serves as a clinically applicable biomarker for prognostication and therapeutic stratification, with potential implications for optimizing immunotherapy and chemotherapy strategies in glioma patients. Microtubule dynamics Glioma M2 macrophage polarization Spatiotemporal heterogeneity Full Text Cite Share Download PDF Status: Published Journal Publication published 28 Feb, 2026 Read the published version in Journal of Translational Medicine → Version 1 posted Reviewers agreed at journal 11 Dec, 2025 Reviewers invited by journal 11 Dec, 2025 Editor assigned by journal 16 Oct, 2025 First submitted to journal 13 Oct, 2025 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. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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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-7855246","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":558889687,"identity":"df1c4705-bb00-4dc1-87d1-8cdddb9562cc","order_by":0,"name":"Xinyu 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Microtubule dynamics regulate tumor progression and immune escape; however, the prognostic significance of microtubule-associated genes in glioma and their immunological significance still lack systematic investigation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003cbr\u003e\n \u003c/strong\u003eWe integrated transcriptomic and clinical data from TCGA and CGGA cohorts to identify microtubule-associated genes with prognostic significance. A risk score (RS) model was established using Cox regression and validated in independent cohorts. Spatial transcriptomics and single-cell RNA sequencing were applied to characterize the expression patterns of candidate genes across glioma microregions and immune cell populations. Functional enrichment analysis, immune infiltration assessment, and drug sensitivity profiling were performed to explore the biological mechanisms and clinical implications of the RS model.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003cbr\u003e\n\u003c/strong\u003eWe identified 18 microtubule-associated genes that are significantly associated with glioma prognosis and constructed a four-gene RS model, which robustly predicts overall survival. Tumors with high-RS exhibited increased infiltration of M2 macrophages, enhanced immunosuppressive signaling, and reduced sensitivity to alkylating agents. Spatial and single-cell analyses confirmed that core RS genes are enriched at the tumor-immune interface and shaped macrophage polarization dynamics.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003cbr\u003e\n\u003c/strong\u003eOur findings highlight microtubule-associated genes as key regulators of the glioma immune microenvironment. 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