Mass spectrometry-based proteomics analyses of post-translational modifications and proteoforms in human pituitary adenomas

Pituitary adenoma (PA) is a common intracranial neoplasm, which affects the hypothalamus-pituitary-target organ axis systems, and is hazardous to human health. Post-translational modifications (PTMs), including phosphorylation, ubiquitination, nitration, and sumoylation, are vitally important in the PA pathogenesis. The large-scale analysis of PTMs could provide a global view of molecular mechanisms for PA. Proteoforms, which are used to define various protein structural and functional forms originated from the same gene, are the future direction of proteomics research. The global studies of different proteoforms and PTMs of hypophyseal hormones such as growth hormone (GH) and prolactin (PRL) and the proportion change of different GH proteoforms or PRL proteoforms in human pituitary tissue could provide new insights into the clinical value of pituitary hormones in PAs. Multiple quantitative proteomics methods, including mass spectrometry (MS)-based label-free and stable isotope-labeled strategies in combination with different PTM-peptide enrichment methods such as TiO2 enrichment of tryptic phosphopeptides and antibody enrichment of other PTM-peptides increase the feasibility for researchers to study PA proteomes. This article reviews the research status of PTMs and proteoforms in PAs, including the enrichment method, technical limitation, quantitative proteomics strategies, and the future perspectives, to achieve the goals of in-depth understanding its molecular pathogenesis, and discovering effective biomarkers and clinical therapeutic targets for predictive, preventive, and personalized treatment of PA patients.