title: Alteration of ASIC1 expression in clear cell renal cell carcinoma.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors: Department of Urology, Fudan University, Shanghai, People's Republic of China.
authors: Yan
authors: Y
authors: Li
authors: Central Laboratory, Jinshan Hospital, Fudan University, Shanghai, People's Republic of China.
authors: Guoxiong
authors: G
authors: Xu
authors: Department of Urology, Fudan University, Shanghai, People's Republic of China.
authors: Kai
authors: K
authors: Huang
authors: Department of Urology, Shanghai First People's Hospital, Medical College of Shanghai Jiao Tong University, Shanghai, People's Republic of China.
authors: Jun
authors: J
authors: Wang
authors: Central Laboratory, Jinshan Hospital, Fudan University, Shanghai, People's Republic of China.
authors: Jihong
authors: J
authors: Zhang
authors: Department of Urology, Fudan University, Shanghai, People's Republic of China.
authors: Jikai
authors: J
authors: Liu
authors: Department of Urology, Fudan University, Shanghai, People's Republic of China.
authors: Zhanyu
authors: Z
authors: Wang
authors: Department of Urology, Fudan University, Shanghai, People's Republic of China.
authors: Gang
authors: G
authors: Chen
keywords: ASIC1; biomarkers; clear cell renal cell carcinoma