Opinion paperUpregulation of cyclin B1 plays potential roles in the invasiveness of pituitary adenomas

- CCNB1 was enhanced with the increased invasive degree in pituitary adenomas.
- CCNB1 was mainly involved in p53 signaling pathway and cell cycle.
- Interactions between CCNB1 and other genes implicated in tumor proliferation.
- Up-regulation of CCNB1 could be an indicator for invasiveness of pituitary adenomas.

Predicting aggressive or malignant behavior of pituitary adenomas (PAs) remains challenging. Aberrant expression of cyclin B1 (CCNB1) occurred in various tumors including PAs. Our study was aimed to explore its roles in the development of PAs aggressiveness. According to the integrated analysis, the expression of CCNB1 was evaluated. Following bioinformatics analysis was performed to uncover the pathways CCNB1 involved in and the upstream transcriptional regulation factors. The mRNA expression of CCNB1 was verified by qRT-PCR. Immunohistochemistry analysis was conducted to examine the expression of CCNB1 protein in three groups of PAs (non-invasive, invasive and aggressive-invasive). In this study, CCNB1 was up-regulated in PAs versus normal pituitary. Functional annotation revealed CCNB1 was mainly involved in p53 signaling pathway and cell cycle, which affected proliferation and contributed to tumorigenesis. The constructed transcriptional regulatory network contained 22 upstream transcriptional factors for CCNB1. Moreover, the network also suggested the interactions between CCNB1 and other genes implicated in proliferation (BUB1, CDC25C and TTK). Immunohistochemistry showed staining of CCNB1 was positive in PAs, and its expression was gradually enhanced with the increased invasiveness. In conclusion, up-regulation of CCNB1, together with other regulatory molecules in cell cycle, may play roles in the PAs pathology and could be an indicator for invasiveness of PAs.