Revealing the complexities of the pituitary tumor microenvironment via single cell and spatial transcriptomic sequencing (Nr. lzp-2025/1-0304)

Pituitary neuroendocrine tumors (PitNETs) are the most common intracranial tumors, yet they rarely metastasize. Pituitary tissue exhibits plasticity, but the mechanisms that prevent cancer development are unclear. This study will use spatial transcriptomics and in vitro cell experiments to investigate SF1-line PitNETs, ​​cell line models, and cancer cells. Objectives: 1) to identify spatial features that prevent malignancy by analyzing cell interactions, cell types, and pituitary plasticity; 2) to investigate the clinical applicability of markers from spatial transcriptomics data of gonadotropic PitNETs by comparing PitNETs with other tumors, searching for new therapeutic targets, and functionally investigating recent findings in the literature. 3) Perform integrated data analysis by linking spatial cell distribution to tumor cell composition and identifying clinical group, lineage and PitNET-specific localizations, biomarkers and common trends compared to other groups as well as reference data including PitNET, cancer and other neuroendocrine tumors, and take into account genetic background in this analysis. Functional experiments will use RNantisense A to investigate the role of genes recently identified in the literature and validate the novel findings of this project to advance the understanding of therapeutic targets for SF1 lineage PitNET. The project aims to uncover PitNET biology, improve treatments and provide information to other cancer research.