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The invasive characteristic of nonfunctional pituitary adenoma (NFPA) is an important clinical problem without a clear molecular mechanism, which severely challenges its treatment strategy. Clarification of the proteomic alterations between invasive and non-invasive NFPAs is the key step for in-depth understanding of its mechanisms and discovering reliably invasive biomarkers. Two-dimensional gel electrophoresis (2DGE)-based comparative proteomics was carried out between four invasive and four non-invasive NFPAs. A total of 64 upregulated protein-spots and 39 downregulated protein-spots were identified among 24 (invasive n = 12; non-invasive n = 12) 2DGE maps (ca. 1200 spots/gel). Mass spectrometry identified 30 upregulated proteins and 27 downregulated proteins between invasive and noninvasive NFPAs. Those 57 differentially expressed proteins are involved in multiple biological functions, including oxidative stress, mitochondrial dysfunction, MAPK signaling alteration, proteolysis abnormality, CDK-C signaling, amyloid processing, and TR/RXR activation. These findings provide important clues to insights into molecular mechanisms of invasive NFPAs and to discovery of effective biomarkers for effective treatment of invasive NFPA patients.

Invasiveness-Related Proteomic Variations and Molecular Network Changes in Human Nonfunctional Pituitary Adenomas