A clinically applicable connectivity signature for glioblastoma includes the tumor network driver CHI3L1
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Published:2024-02-06
Issue:1
Volume:15
Page:
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ISSN:2041-1723
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Container-title:Nature Communications
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language:en
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Short-container-title:Nat Commun
Author:
Hai LingORCID, Hoffmann Dirk C.ORCID, Wagener Robin J., Azorin Daniel D., Hausmann David, Xie Ruifan, Huppertz Magnus-Carsten, Hiblot JulienORCID, Sievers PhilippORCID, Heuer Sophie, Ito Jakob, Cebulla Gina, Kourtesakis Alexandros, Kaulen Leon D., Ratliff MiriamORCID, Mandelbaum Henriette, Jung Erik, Jabali Ammar, Horschitz Sandra, Ernst Kati J.ORCID, Reibold Denise, Warnken Uwe, Venkataramani Varun, Will RainerORCID, Suvà Mario L.ORCID, Herold-Mende Christel, Sahm FelixORCID, Winkler FrankORCID, Schlesner MatthiasORCID, Wick WolfgangORCID, Kessler TobiasORCID
Abstract
AbstractTumor microtubes (TMs) connect glioma cells to a network with considerable relevance for tumor progression and therapy resistance. However, the determination of TM-interconnectivity in individual tumors is challenging and the impact on patient survival unresolved. Here, we establish a connectivity signature from single-cell RNA-sequenced (scRNA-Seq) xenografted primary glioblastoma (GB) cells using a dye uptake methodology, and validate it with recording of cellular calcium epochs and clinical correlations. Astrocyte-like and mesenchymal-like GB cells have the highest connectivity signature scores in scRNA-sequenced patient-derived xenografts and patient samples. In large GB cohorts, TM-network connectivity correlates with the mesenchymal subtype and dismal patient survival. CHI3L1 gene expression serves as a robust molecular marker of connectivity and functionally influences TM networks. The connectivity signature allows insights into brain tumor biology, provides a proof-of-principle that tumor cell TM-connectivity is relevant for patients’ prognosis, and serves as a robust prognostic biomarker.
Funder
Deutsches Krebsforschungszentrum Deutsche Forschungsgemeinschaft
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary
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