HRA003588
(Controlled Access)
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Pituitary neuroendocrine tumor (PitNET) is one of the most common intracranial tumors. Here, we performed the largest integrative genomics, transcriptomics, proteomics, and phosphoproteomics analysis reported to date in a cohort of 200 PitNET patients. Genomics data indicated that GNAS copy number gain can serve as a reliable diagnostic marker for hyperproliferation of the PIT1 lineage. Proteomics-based classification of PitNETs identified 7 clusters, among which, tumors overexpressing epithelial-mesenchymal transition (EMT) markers clustered into a more invasive subgroup. Further analysis identified potential therapeutic targets, including CDK6, TWIST1, EGFR, and VEGFR2, for different clusters. Immune subtyping to explore the potential for application of immunotherapy in PitNET identified an association between alterations in the JAK1-STAT1-PDL1 axis and immune exhaustion and between changes in the JAK3-STAT6-FOS/JUN axis and immune infiltration. |