TY  - JOUR
AU  - Hai, Ling
AU  - Hoffmann, Dirk Carsten Frieder
AU  - Wagener, Robin J
AU  - Azorin, Daniel D
AU  - Hausmann, David
AU  - Xie, Ruifan
AU  - Huppertz, Magnus-Carsten
AU  - Hiblot, Julien
AU  - Sievers, Philipp
AU  - Heuer, Sophie
AU  - Ito, Jakob
AU  - Cebulla, Gina
AU  - Kourtesakis, Alexandros
AU  - Kaulen, Leon D
AU  - Ratliff, Miriam
AU  - Mandelbaum, Henriette
AU  - Jung, Erik
AU  - Jabali, Ammar
AU  - Horschitz, Sandra
AU  - Ernst, Kati
AU  - Reibold, Denise
AU  - Warnken, Uwe
AU  - Venkataramani, Varun
AU  - Will, Rainer
AU  - Suvà, Mario L
AU  - Herold-Mende, Christel
AU  - Sahm, Felix
AU  - Winkler, Frank
AU  - Schlesner, Matthias
AU  - Wick, Wolfgang
AU  - Kessler, Tobias
TI  - A clinically applicable connectivity signature for glioblastoma includes the tumor network driver CHI3L1.
JO  - Nature Communications
VL  - 15
IS  - 1
SN  - 2041-1723
CY  - [London]
PB  - Nature Publishing Group UK
M1  - DKFZ-2024-00289
SP  - 968
PY  - 2024
N1  - #EA:W610#EA:B320#LA:B320#
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:38320988
DO  - DOI:10.1038/s41467-024-45067-8
UR  - https://inrepo02.dkfz.de/record/287645
ER  -