Integrated proteomic and metabolomic profiling reveals molecular signatures underlying invasiveness in...

Pituitary adenomas constitute 10 to 25% of intracranial tumors, rendering them one of the most prevalent types of brain tumors. While the majority of pituitary adenomas are benign, ~35% exhibit invasive behavior. Compared with their non-invasive counterparts, invasive pituitary adenomas are more challenging to manage, highlighting the need to elucidate their underlying pathogenesis. However, the molecular mechanisms driving the invasive behavior of these tumors remain incompletely understood. Thus, the present study employed an integrated proteomic and metabolomic approach to investigate the molecular features associated with tumor invasiveness in pituitary adenomas. The investigation was performed at the First Affiliated Hospital of Xiamen University (Xiamen, China). Fresh-frozen tumor specimens were collected from 16 patients diagnosed with clinically non-functioning pituitary adenomas. These samples were divided into two groups based on invasiveness: Invasive tumors (n=8; Knosp grade ≥2) and non-invasive tumors (n=8; Knosp grade <2). Using data-independent acquisition mass spectrometry (MS) in conjunction with liquid chromatography-MS/MS metabolomics analysis, differentially expressed proteins (DEPs) and differentially expressed metabolites (DEMs) were identified. Comparative analysis identified 614 DEPs, including 286 proteins that were upregulated and 328 that were downregulated in invasive tumors relative to non-invasive tumors. Additionally, 74 DEMs were found, comprising 42 increased and 32 decreased metabolites. Enrichment analysis of pathways revealed notable involvement of the cyclic adenosine monophosphate (cAMP) signaling cascade, pathways related to pathogenic Escherichia coli (E. coli) infection and the synaptic vesicle cycle. Integration of the proteomic and metabolomic data underscored consistent changes within these biological pathways. The present investigation represents a comprehensive effort to combine proteomic and metabolomic approaches to characterize the invasive phenotype of pituitary adenomas. The identification of enriched pathways associated with cAMP signaling, E. coli infection and synaptic vesicle cycling provides new mechanistic understanding and offers potential biomarkers or therapeutic targets for differentiating tumor aggressiveness.