Journal Article

DKFZ-2024-00289

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png A clinically applicable connectivity signature for glioblastoma includes the tumor network driver CHI3L1.

Hai, L. (First author)DKFZ* ; Hoffmann, D. C. F. (First author)DKFZ* ; Wagener, R. J.DKFZ* ; Azorin, D. D.DKFZ* ; Hausmann, D.DKFZ* ; Xie, R.DKFZ* ; Huppertz, M.-C. ; Hiblot, J. ; Sievers, P.DKFZ* ; Heuer, S.DKFZ* ; Ito, J.DKFZ* ; Cebulla, G.DKFZ* ; Kourtesakis, A.DKFZ* ; Kaulen, L. D.DKFZ* ; Ratliff, M.DKFZ* ; Mandelbaum, H. ; Jung, E.DKFZ* ; Jabali, A. ; Horschitz, S. ; Ernst, K.DKFZ* ; Reibold, D.DKFZ* ; Warnken, U.DKFZ* ; Venkataramani, V.DKFZ* ; Will, R.DKFZ* ; Suvà, M. L. ; Herold-Mende, C. ; Sahm, F.DKFZ* ; Winkler, F.DKFZ* ; Schlesner, M.DKFZ* ; Wick, W.DKFZ* ; Kessler, T. (Last author)DKFZ*

2024
Nature Publishing Group UK [London]

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Please use a persistent id in citations: doi:10.1038/s41467-024-45067-8

Abstract: 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.

Note: #EA:W610#EA:B320#LA:B320#

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Contributing Institute(s):

1. Core Facility Omics IT (W610)
2. KKE Neuroonkologie (B320)
3. KKE Neuropathologie (B300)
4. Pädiatische Gliomforschung (B360)
5. Zelluläre Tools (W111)
6. DKTK HD zentral (HD01)

Research Program(s):

1. 312 - Funktionelle und strukturelle Genomforschung (POF4-312) (POF4-312)

Appears in the scientific report 2024

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