Jin Yan, Zhou Hong, Gong Lei, Xia Jiazeng, Yu Guanzhen, Chen Yigang
Department of Gastroenterology, Wuxi Second Hospital, Nanjing Medical University Jiangsu, People's Republic of China.
Department of General Surgery, Wuxi Second Hospital, Nanjing Medical University Jiangsu, People's Republic of China.
Int J Clin Exp Pathol. 2017 Nov 1;10(11):10802-10811. eCollection 2017.
UCH-L1 has been implicated to playing a potential role in cancer development and progression. However, UCH-L1's role in hilar cholangiocarcinoma remains unclear.
The function of UCH-L1 in hilar cholangiocarcinoma was evaluated using human tissues, molecular and cell biology, and animal models, and its prognostic significance was determined according to its impact on patient survival.
In the present study, UCH-L1 was overexpressed in 62.1% of patients with primary hilar cholangiocarcinoma. Overexpression of UCH-L1 is associated with large tumor size, advanced tumor stage, lymph node metastasis, advanced TNM stage, and high CA19-9 levels, and is also correlated with poor survival rates. Silencing of UCH-L1 inhibited proliferation, colony formation of hilar cholangiocarcinoma cells in vitro and suppressed tumor growth of hilar cholangiocarcinoma cells in vivo. We also observed that silencing of UCH-L1 decreased the phosphorylation level of Akt and PCNA in the xenograft experiments.
Taken together, these findings suggest that UCH-L1 functions as an oncogene in the development and progression of hilar cholangiocarcinoma. UCH-L1 can serve as an independent prognostic factor and maybe a potential therapeutic target for patients with hilar cholangiocarcinoma.
泛素羧基末端水解酶L1(UCH-L1)被认为在癌症的发生和发展中发挥潜在作用。然而,UCH-L1在肝门部胆管癌中的作用仍不清楚。
利用人体组织、分子和细胞生物学以及动物模型评估UCH-L1在肝门部胆管癌中的功能,并根据其对患者生存的影响确定其预后意义。
在本研究中,62.1%的原发性肝门部胆管癌患者中UCH-L1过表达。UCH-L1的过表达与肿瘤体积大、肿瘤分期晚、淋巴结转移、TNM分期晚以及CA19-9水平高相关,也与生存率低相关。沉默UCH-L1可抑制肝门部胆管癌细胞的增殖、体外集落形成,并在体内抑制肝门部胆管癌细胞的生长。我们还观察到,在异种移植实验中,沉默UCH-L1可降低Akt和增殖细胞核抗原(PCNA)的磷酸化水平。
综上所述,这些发现表明UCH-L1在肝门部胆管癌的发生和发展中起癌基因作用。UCH-L1可作为独立的预后因素,可能是肝门部胆管癌患者的潜在治疗靶点。