Diagnosis of invasive non-functional pituitary adenomas using exosomal biomarkers

Background and aims: Incomplete surgical resection of invasive non-functional pituitary adenomas (NFPAs) produces a risk of the subsequent development of complications which will require treatment with powerful drugs and adjuvant radiotherapy. Materials and methods: The degree of invasiveness of NFPA can be established using biomarkers to help clinicians choose appropriate treatment for these patients. Results: This research explored transcriptomic and proteomic variations of non-invasive and invasive NFPAs, other forms of pituitary adenomas and evaluated exosomal genetic markers associated with these diseases. Increased expression of matrix metalloproteinase-1 (MMP1) and its formation in exosomes (exo-MMP1) were correlated with the characteristic invasiveness of NFPAs. Changes in the expression of MMP1 in the exosome was synchronized with transduction of NFPA cells. Enrichment of MMP1 stimulated migration, growth and angiogenesis in tumors through the protease-activated receptor-1 signaling pathway in cells. Conclusion: The results revealed that MMP1 activity has obligatory actions in promoting tumor invasion and angiogenesis, and that the exosome-mediated regulatory pathway for MMP1 may be a novel therapeutic target.