Zhao Peng, Zhang Pengfei, Hu Wei, Wang Hongyun, Yu Guoqiang, Wang Zhuang, Li Chuzhong, Bai Jiwei, Zhang Yazhuo
Department of Neurosurgery, Beijing Tian Tan Hospital, Capital Medical University, Beijing, China.
Department of Neurosurgery, Beijing Tian Tan Hospital, Capital Medical University, Beijing, China.
J Clin Neurosci. 2017 Sep;43:267-273. doi: 10.1016/j.jocn.2017.05.005. Epub 2017 Jun 7.
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.
预测垂体腺瘤(PA)的侵袭性或恶性行为仍然具有挑战性。细胞周期蛋白B1(CCNB1)在包括PA在内的各种肿瘤中均有异常表达。我们的研究旨在探讨其在PA侵袭性发展中的作用。通过综合分析评估CCNB1的表达。随后进行生物信息学分析以揭示CCNB1涉及的信号通路和上游转录调控因子。通过qRT-PCR验证CCNB1的mRNA表达。进行免疫组织化学分析以检测三组PA(非侵袭性、侵袭性和侵袭性-侵袭性)中CCNB1蛋白的表达。在本研究中,与正常垂体相比,PA中CCNB1上调。功能注释显示CCNB1主要参与p53信号通路和细胞周期,影响增殖并促进肿瘤发生。构建的转录调控网络包含CCNB1的22个上游转录因子。此外,该网络还提示了CCNB1与其他参与增殖的基因(BUB1、CDC25C和TTK)之间的相互作用。免疫组织化学显示PA中CCNB1染色呈阳性,且其表达随侵袭性增加而逐渐增强。总之,CCNB1的上调以及细胞周期中的其他调控分子可能在PA的病理过程中起作用,并且可能是PA侵袭性的一个指标。