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Hai, Ling; Hoffmann, Dirk C.; Wagener, Robin J.; Azorin, Daniel D.; Hausmann, David; Xie, Ruifan; Huppertz, Magnus-Carsten; Hiblot, Julien; Sievers, Philipp; Heuer, Sophie; Ito, Jakob; Cebulla, Gina; Kourtesakis, Alexandros; Kaulen, Leon D.; Ratliff, Miriam; Mandelbaum, Henriette; Jung, Erik; Jabali, Ammar; Horschitz, Sandra; Ernst, Kati J.; Reibold, Denise; Warnken, Uwe; Venkataramani, Varun; Will, Rainer; [...]

A clinically applicable connectivity signature for glioblastoma includes the tumor network driver CHI3L1

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  • Media type: E-Article
  • Title: A clinically applicable connectivity signature for glioblastoma includes the tumor network driver CHI3L1
  • Contributor: Hai, Ling; Hoffmann, Dirk C.; Wagener, Robin J.; Azorin, Daniel D.; Hausmann, David; Xie, Ruifan; Huppertz, Magnus-Carsten; Hiblot, Julien; Sievers, Philipp; Heuer, Sophie; Ito, Jakob; Cebulla, Gina; Kourtesakis, Alexandros; Kaulen, Leon D.; Ratliff, Miriam; Mandelbaum, Henriette; Jung, Erik; Jabali, Ammar; Horschitz, Sandra; Ernst, Kati J.; Reibold, Denise; Warnken, Uwe; Venkataramani, Varun; Will, Rainer; [...]
  • imprint: Springer Science and Business Media LLC, 2024
  • Published in: Nature Communications
  • Language: English
  • DOI: 10.1038/s41467-024-45067-8
  • ISSN: 2041-1723
  • Keywords: General Physics and Astronomy ; General Biochemistry, Genetics and Molecular Biology ; General Chemistry ; Multidisciplinary
  • Origination:
  • Footnote:
  • Description: <jats:title>Abstract</jats:title><jats:p>Tumor 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. <jats:italic>CHI3L1</jats:italic> 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.</jats:p>
  • Access State: Open Access