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

ABSTRACT: 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.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Permanent Cell Line Cell, Cell Culture

DISEASE(S): Brain Cancer

SUBMITTER: Tobias Kessker  

LAB HEAD: Wolfgang Wick

PROVIDER: PXD044001 | Pride | 2023-11-27

REPOSITORIES: Pride