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

Tumor microtubes (TMs) connect glioma cells to a network with considerable relevance for tumor progression and therapy resistance. The determination of TM-interconnectivity in individual tumors has been challenging and the impact on patient survival unresolved. Here, a connectivity signature from single-cell RNA-sequenced (scRNA-Seq) xenografted primary glioblastoma (GB) cells has been established using a dye uptake methodology, confirmed with recording of cellular calcium epochs and validated with 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, network connectivity correlated with the mesenchymal subtype and dismal patient survival. CHI3L1 has been identified and validated as a robust molecular marker of connectivity with functional relevance. The connectivity signature allows novel 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.

Type: Other
Archiver: European Genome-Phenome Archive (EGA)

1 Dataset 1 Publication

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Dataset ID	Description	Technology	Samples
EGAD00001012235	This dataset contains RNA Seq, 10x scRNA Seq and Exome sequencing of glioblastoma samples. Sequencing was performed on a Illumina NovaSeq 6000 and Illumina HiSeq 4000. The sequencing was always paired.	Illumina HiSeq 4000 Illumina NovaSeq 6000	61

Publications	Citations
A clinically applicable connectivity signature for glioblastoma includes the tumor network driver CHI3L1. Hai L, Hoffmann DC, Wagener RJ, Azorin DD, Hausmann D, Xie R, Huppertz MC, Hiblot J, Sievers P, Heuer S, Ito J, Cebulla G, Kourtesakis A, Kaulen LD, Ratliff M, Mandelbaum H, Jung E, Jabali A, Horschitz S, Ernst KJ, Reibold D, Warnken U, Venkataramani V, Will R, Suvà ML, Herold-Mende C, Sahm F, Winkler F, Schlesner M, Wick W, Kessler T. Nat Commun 15: 2024 968	5

Publications

Citations

A clinically applicable connectivity signature for glioblastoma includes the tumor network driver CHI3L1.
Hai L, Hoffmann DC, Wagener RJ, Azorin DD, Hausmann D, Xie R, Huppertz MC, Hiblot J, Sievers P, Heuer S, Ito J, Cebulla G, Kourtesakis A, Kaulen LD, Ratliff M, Mandelbaum H, Jung E, Jabali A, Horschitz S, Ernst KJ, Reibold D, Warnken U, Venkataramani V, Will R, Suvà ML, Herold-Mende C, Sahm F, Winkler F, Schlesner M, Wick W, Kessler T. Nat Commun 15: 2024 968