%0 Journal Article
%A Hai, Ling
%A Hoffmann, Dirk Carsten Frieder
%A Wagener, Robin J
%A Azorin, Daniel D
%A Hausmann, David
%A Xie, Ruifan
%A Huppertz, Magnus-Carsten
%A Hiblot, Julien
%A Sievers, Philipp
%A Heuer, Sophie
%A Ito, Jakob
%A Cebulla, Gina
%A Kourtesakis, Alexandros
%A Kaulen, Leon D
%A Ratliff, Miriam
%A Mandelbaum, Henriette
%A Jung, Erik
%A Jabali, Ammar
%A Horschitz, Sandra
%A Ernst, Kati
%A Reibold, Denise
%A Warnken, Uwe
%A Venkataramani, Varun
%A Will, Rainer
%A Suvà, Mario L
%A Herold-Mende, Christel
%A Sahm, Felix
%A Winkler, Frank
%A Schlesner, Matthias
%A Wick, Wolfgang
%A Kessler, Tobias
%T A clinically applicable connectivity signature for glioblastoma includes the tumor network driver CHI3L1.
%J Nature Communications
%V 15
%N 1
%@ 2041-1723
%C [London]
%I Nature Publishing Group UK
%M DKFZ-2024-00289
%P 968
%D 2024
%Z #EA:W610#EA:B320#LA:B320#
%X 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. 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.
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:38320988
%R 10.1038/s41467-024-45067-8
%U https://inrepo02.dkfz.de/record/287645