EMT-Related Markers in Serum Exosomes are Potential Diagnostic Biomarkers for Invasive Pituitary Adenomas.

ABSTRACT

PURPOSE: Assessing the invasiveness of pituitary adenomas (PAs) is critical to making the best surgical and treatment plan. However, it is difficult to determine the invasiveness of pituitary adenomas based on current clinical methods, such as imaging and histological methods. The present article aims to investigate noninvasive methods to discover viable biomarkers for invasive pituitary adenomas and provide a basis for early intervention of pituitary adenomas. METHODS: E-cadherin, N-cadherin, Epcam, TGF-ß, Smad3, and Smad7 were detected in the tissues and exosomes in 10 cases of invasive PAs and 10 cases of noninvasive PAs by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR), Western blotting, and immunohistochemical analysis. RESULTS: Compared with that in the noninvasive group, the expression of N-cad in the exosomes of the invasive group was significantly increased, and the expression of E-cad and Epcam was reduced. In the invasive group, the expression levels of TGF-ß1 and Smad3 were reduced. These results were consistent across exosomes and groups. In further cell experiments, the EMT ratio in the SIS3 treatment group, and especially in the TGF-ß1 plus SIS3 treatment group (P <0.001), was significantly increased, and the EMT ratio was significantly lower when one-half the dose of TGF-ß and SIS3. CONCLUSION: The results indicate that EMT-related biomarkers in serum exosomes can be potentially used for assessing the invasiveness of pituitary adenoma.