Li Yan, Xu Guoxiong, Huang Kai, Wang Jun, Zhang Jihong, Liu Jikai, Wang Zhanyu, Chen Gang
Department of Urology, Fudan University, Shanghai, People's Republic of China.
Central Laboratory, Jinshan Hospital, Fudan University, Shanghai, People's Republic of China.
Onco Targets Ther. 2015 Aug 14;8:2121-7. doi: 10.2147/OTT.S86927. eCollection 2015.
Acidic extracellular pH is a major feature of tumor tissue. Acid-sensing ion channels (ASICs) represent an H(+)-gated subgroup of the degenerin/epithelial Na(+) channel family and are activated by acidic microenvironment. Little is known about the expression and clinical significance of ASICs in solid tumors. The purpose of this study was to examine the expression of ASIC1 in human clear cell renal cell carcinoma (CCRCC) and to determine if the expression of ASIC1 is associated with clinicopathological features.
The expression of ASIC1 in CCRCC tissues at the mRNA and protein levels was determined by real-time quantitative polymerase chain reaction and Western blot analysis, respectively. A tissue microarray was used to assess the expression of ASIC1 protein in tumor tissue and matched adjacent normal tissues from 75 patients with CCRCC.
ASIC1 expression was detected in normal renal and CCRCC samples. The expressions of ASIC1 protein and mRNA were significantly decreased in the CCRCC tissues compared with matched normal renal tissues (P<0.05). The staining density measurement showed that the expression of ASIC1 was significantly decreased in stage I (P=0.037), stage II (P=0.026), and stage III (P=0.026), grades I-II CCRCC (P=0.004), and CCRCC from male patients (P=0.00002). However, no significant difference was observed for ASIC1 expression between CCRCC and normal tissue in patients with stage IV CCRCC (P=0.236), patients with grades III-IV CCRCC (P=0.314), and female patients (P=0.095). Spearman correlations demonstrated that ASIC1 expression did not correlate to tumor stage (correlation coefficient [CC =0.168], P=0.149) and the age of patients (CC -0.147, P=0.688) but showed a positive correlation to higher tumor grades (CC =0.270, P=0.018).
ASIC1 is downregulated in CCRCC. ASIC1 expression may be potentially used as a novel biomarker and even a CCRCC therapeutic target. Further efforts will be made to clarify the mechanism of ASIC1 in occurrence, progression, and metastasis of CCRCC.
细胞外酸性pH值是肿瘤组织的一个主要特征。酸敏感离子通道（ASICs）是退化素/上皮钠通道家族的一个H⁺门控亚组，可被酸性微环境激活。关于ASICs在实体瘤中的表达及临床意义知之甚少。本研究旨在检测ASIC1在人透明细胞肾细胞癌（CCRCC）中的表达，并确定ASIC1的表达是否与临床病理特征相关。
分别通过实时定量聚合酶链反应和蛋白质印迹分析测定CCRCC组织中ASIC1在mRNA和蛋白质水平的表达。使用组织芯片评估75例CCRCC患者肿瘤组织及配对的相邻正常组织中ASIC1蛋白的表达。
在正常肾组织和CCRCC样本中均检测到ASIC1表达。与配对的正常肾组织相比，CCRCC组织中ASIC1蛋白和mRNA的表达显著降低（P<0.05）。染色密度测量显示，在Ⅰ期（P=0.037）、Ⅱ期（P=0.026）和Ⅲ期（P=0.026）、Ⅰ - Ⅱ级CCRCC（P=0.004）以及男性患者的CCRCC（P=0.00002）中，ASIC1的表达显著降低。然而，在Ⅳ期CCRCC患者（P=0.236）、Ⅲ - Ⅳ级CCRCC患者（P=0.314）和女性患者（P=0.095）的CCRCC与正常组织之间，未观察到ASIC1表达的显著差异。Spearman相关性分析表明，ASIC1表达与肿瘤分期（相关系数[CC]=0.168，P=0.149）和患者年龄（CC=-0.147，P=0.688）无关，但与较高的肿瘤分级呈正相关（CC=0.270，P=0.018）。
ASIC1在CCRCC中表达下调。ASIC1表达可能潜在地用作一种新型生物标志物，甚至是CCRCC的治疗靶点。将进一步努力阐明ASIC1在CCRCC发生、发展和转移中的机制。
