CNSC-33. TRANSCRIPTOMIC NEURON-TUMOR INTERACTION MAPPING OF EXTRACRANIAL TUMORS AND BRAIN METASTASES

Abstract

Abstract Ongoing efforts in the field of Cancer Neuroscience seek to improve the understanding of neuron-cancer interactions and their effects on tumor progression. In glioma, synaptic neuronal input to tumor cells drives tumor progression and invasion. Even though neuron-cancer interactions have been described in brain metastases and extracranial tumors as well, the mechanisms of action between the nervous system and tumor cells are incompletely understood. Systematic transcriptomic analyses to detect overarching principles of neuron-tumor interaction have been lacking so far. Here, we performed focused integrative transcriptomic and proteomic analyses in more than 10 different extracranial tumor entities and brain metastases to analyse potential neuron-tumor interactions.Neurotransmitters receptor genes were heterogeneously expressed across extracranial tumor entities and brain metastases. We used Markov Affinity-based Graph Imputation of Cells to recover gene-gene relationships to robustly identify more than 50 initial gene co-expression networks (GCNs) associated with neurotransmitter genes. Molecular pathways that are associated with neurotransmitter receptor gene expression show heterogenous and overlapping neuronal gene expression programs in tumor cell subpopulations. While some GCNs showed overarching expression patterns of neuronal interactions across many entities including brain metastases as well as extracranial tumors, some GCNs were specialised signatures for certain tumor types. To characterise underlying gene regulatory networks, we performed transcription factor analyses. Certain GCNs were clearly associated with specific transcriptional regulators and known tumor biological functions. To validate our results, we further analysed the GCNs in bulk RNA datasets as well as on a protein level. We were able to identify neuronal gene expression patterns that were associated with worse survival across certain tumor entities.The results suggest that brain metastases and extracranial tumors have multiple biologically relevant mechanisms of interaction with the nervous system. These analyses are the foundation for further validation and clinical translation.