丙酮酸激酶M2在人膀胱癌中的表达及其与临床参数和预后的相关性。
Expression of pyruvate kinase M2 in human bladder cancer and its correlation with clinical parameters and prognosis.
作者信息
Huang Changkun, Huang Zhichao, Bai Peiming, Luo Guangcheng, Zhao Xiaokun, Wang Xinjun
机构信息
Department of Urology, The Second Xiangya Hospital, Central South University, Changsha, People's Republic of China.
Department of Urology, Zhongshan Hospital, Xiamen University, Xiamen, People's Republic of China.
出版信息
Onco Targets Ther. 2018 Apr 11;11:2075-2082. doi: 10.2147/OTT.S152999. eCollection 2018.
BACKGROUND
Pyruvate kinase M2 (PKM2) is a key regulator of the Warburg effect and has critical functions in glycolysis, contributing to the Warburg effect, tumor growth, angiogenesis, cell division, metastasis, and apoptosis. The high expression of PKM2 in various solid tumors renders it a potential biomarker of tumorigenesis and tumor invasion, but the expression and role of PKM2 in bladder cancer have not been studied extensively.
PATIENTS AND METHODS
Western blot and immunohistochemistry (IHC) were used to measure the expression of PKM2, and quantitative real-time polymerase chain reaction (PCR) was performed to determine PKM2 mRNA levels. The relationships between PKM2 expression and clinicopathological parameters and prognosis were analyzed using the Kaplan-Meier plots and a Cox proportional hazards regression model.
RESULTS
Compared with paired adjacent normal bladder tissues, PKM2 mRNA and protein levels were found to be higher in urothelial carcinoma of the bladder (UCB) samples by real-time PCR and Western blot. By IHC, high expression of PKM2 was seen in 117 of 215 UCBs (54.4%) and in eight of 90 adjacent normal bladder tissues (8.9%). The expression of PKM2 was significantly associated with grade, stage, and lymph node status (<0.001). In the univariate survival analysis, a significant association between PKM2 expression and shorter patient survival was observed (<0.001). In different subsets of UCB patients, we found that PKM2 expression was a prognostic factor in patients with G2 (=0.009), G3 (<0.001), pTa/pTis (=0.006), pT1, pT2-4, and pN disease (<0.001). Importantly, PKM2 expression (=0.003), with tumor histological grade (<0.001), pT (<0.001), and pN status (=0.005), was a significant independent prognostic parameter in the multivariate analysis.
CONCLUSION
PKM2 protein and mRNA are upregulated in UCBs and may serve as molecular markers for a poor prognosis in patients with UCB.
背景
丙酮酸激酶M2（PKM2）是瓦伯格效应的关键调节因子，在糖酵解中具有关键作用，有助于瓦伯格效应、肿瘤生长、血管生成、细胞分裂、转移和凋亡。PKM2在各种实体瘤中的高表达使其成为肿瘤发生和肿瘤侵袭的潜在生物标志物，但PKM2在膀胱癌中的表达和作用尚未得到广泛研究。
患者与方法
采用蛋白质印迹法和免疫组织化学（IHC）检测PKM2的表达，并进行定量实时聚合酶链反应（PCR）以确定PKM2 mRNA水平。使用Kaplan-Meier曲线和Cox比例风险回归模型分析PKM2表达与临床病理参数及预后之间的关系。
结果
通过实时PCR和蛋白质印迹法发现，与配对的相邻正常膀胱组织相比，膀胱尿路上皮癌（UCB）样本中PKM2 mRNA和蛋白水平更高。通过免疫组织化学检测，215例UCB中有117例（54.4%）PKM2高表达，90例相邻正常膀胱组织中有8例（8.9%）PKM2高表达。PKM2的表达与分级、分期和淋巴结状态显著相关（<0.001）。在单因素生存分析中，观察到PKM2表达与患者较短生存期之间存在显著关联（<0.001）。在不同亚组的UCB患者中，我们发现PKM2表达是G2（=0.009）、G3（<0.001）、pTa/pTis（=0.006）、pT1、pT2 - 4和pN期疾病（<0.001）患者的预后因素。重要的是，在多因素分析中，PKM2表达（=0.003）与肿瘤组织学分级（<0.001）、pT（<0.001）和pN状态（=0.005）是显著的独立预后参数。
结论
PKM2蛋白和mRNA在UCB中上调，可能作为UCB患者预后不良的分子标志物。
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