Wei Wei, Wang Minggang, Li Yunglong, Meng Qinggui, Tang Yong, Lu Haoyuan, Yu Wenchao, Cheng Qiwei, Li You, Xu Long, Jian Shaojun, Wu Yuexian, Yi Xianlin, Xie Keji
Department of Radiology, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
Department of Urology, Affiliated Hospital of Qinghai University, Xining, Qinghai 810016, P.R. China.
Oncol Lett. 2018 Jul;16(1):775-784. doi: 10.3892/ol.2018.8715. Epub 2018 May 16.
The objective of the present study was to explore the association between muscarinic cholinergic signaling and urothelial bladder tumors. Possible associations among overactive bladder (OAB) symptoms and bladder tumors were retrospectively investigated using a multicenter Chinese database with prospectively collected data since 2010. Firstly, it was demonstrated that OAB symptoms, such as urgency, were more severe in patients with invasive bladder cancer and were associated with a reduced prognosis. Following this, muscarinic cholinergic receptor 3 (M3R) expression in urothelium was determined to be lower in invasive cancer tissue than in adjacent non-cancerous tissue, yet M3R upregulation was associated with a reduced progression free survival (PFS) time. Additionally, it was also demonstrated that muscarinic cholinergic receptor 2 (M2R) was upregulated in the sub-urothelium, and this was also associated with a reduced PFS time. Furthermore, it was determined that cholinesterase and acetylcholinesterase were lower in invasive cancer than in non-invasive cancer. In conclusion, the results indicated that M3R expression was downregulated in invasive bladder cancer, which may have a role as a protective anti-oncogene, in contrast to its oncogenic role in numerous other cancer types. Therefore, muscarinic cholinergic signaling may be a novel therapeutic target for treating bladder cancer.
本研究的目的是探讨毒蕈碱胆碱能信号与膀胱尿路上皮肿瘤之间的关联。使用一个自2010年起前瞻性收集数据的多中心中国数据库，对膀胱过度活动症（OAB）症状与膀胱肿瘤之间可能的关联进行了回顾性研究。首先，研究表明，尿急等OAB症状在浸润性膀胱癌患者中更为严重，且与预后不良相关。在此之后，研究确定浸润性癌组织中尿路上皮的毒蕈碱胆碱能受体3（M3R）表达低于相邻的非癌组织，但M3R上调与无进展生存期（PFS）缩短相关。此外，研究还表明，膀胱黏膜下层的毒蕈碱胆碱能受体2（M2R）上调，这也与PFS缩短相关。此外，研究确定浸润性癌中的胆碱酯酶和乙酰胆碱酯酶低于非浸润性癌。总之，结果表明浸润性膀胱癌中M3R表达下调，这可能具有保护性抗癌基因的作用，与其在许多其他癌症类型中的致癌作用相反。因此，毒蕈碱胆碱能信号可能是治疗膀胱癌的一个新的治疗靶点。
