已发表论文

在肾透明细胞癌中 ASIC1 表达的变化

 

Authors Li Y, Xu G, Huang K, Wang J, Zhang J, Liu J, Wang Z, Chen G
Received 19 April 2015
Accepted for publication 27 May 2015
Published 14 August 2015 Volume 2015:8 Pages 2121—2127
DOI http://dx.doi.org/10.2147/OTT.S86927
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 4
Editor who approved publication:  Professor Daniele Santini


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 (<0.05). The staining density measurement showed that the expression of ASIC1 was significantly decreased in stage I (=0.037), stage II (=0.026), and stage III (=0.026), grades I–II CCRCC (=0.004), and CCRCC from male patients (=0.00002). However, no significant difference was observed for ASIC1 expression between CCRCC and normal tissue in patients with stage IV CCRCC (=0.236), patients with grades III–IV CCRCC (=0.314), and female patients (=0.095). Spearman correlations demonstrated that ASIC1 expression did not correlate to tumor stage (correlation coefficient [CC =0.168], =0.149) and the age of patients (CC -0.147, =0.688) but showed a positive correlation to higher tumor grades (CC =0.270, =0.018).
Conclusion: 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.
Keywords: ASIC1, biomarkers, clear cell renal cell carcinoma