Systematic proteomic analysis of neuroimaging metrics identifies therapeutic targets for pituitary neuroendocrine

The relationship between proteomics and neuroimaging metrics (NIMs) is still not fully understood. By examining the specific proteins expressed in different NIMs, researchers can gain insights into how these NIMs contribute to pituitary neuroendocrine tumors (PitNETs), ultimately enabling the development of targeted interventions and treatments. We identified 15 significantly NIMs and 18 proteins that exhibit a noteworthy causal relationship with the risk of developing PitNETs by forward MR analysis. Additionally, 10 proteins and one distinct neuroimaging metric with PitNETs. Then, the MR results indicated the identification of 33 significant relationships, which connect proteins with NIMs across five distinct categories. Then, we discovered that NIMs are capable of mediating 63% of the inverse relationship observed between WNT3 and the phenotypic characteristics of PitNETs. The results also suggested that WNT3 was associated with hypothalamic function, pituitary function, thyroid function, adrenal function, and gonadal function. Additionally, WNT3 expression was higher in PitNETs and was verified in multiple datasets. This research effectively connects the roles of protein markers with the structures of the brain and the PitNETs that can affect it. By establishing this link, the study provides valuable insights that can help in understanding the complex mechanisms that contribute to PitNETs.