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

Nat Commun. 2024 Feb 6;15(1):968. doi: 10.1038/s41467-024-45067-8.ABSTRACTTumor 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.PMID:38320988 | PMC:PMC10847113 | DOI:10.1038/s41467-024-45067-8
Source: Genomics Proteomics ... - Category: Genetics & Stem Cells Authors: Source Type: research