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Alteration of ASIC1 expression in clear cell renal cell carcinoma.

Li Y, Xu G, Huang K, Wang J, Zhang J, Liu J, Wang Z, Chen G - Onco Targets Ther (2015)

Bottom Line: 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).

View Article: PubMed Central - PubMed

Affiliation: Department of Urology, Fudan University, Shanghai, People's Republic of China.

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).

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.

No MeSH data available.


Related in: MedlinePlus

ASIC1 mRNA expression in matched tumor and normal kidney samples.Notes: The expression level of ASIC1 mRNA was sixfold higher in the normal tissue than that in the tumor tissue. *Represents P<0.05 and n=8.Abbreviation: ASIC1, acid-sensing ion channel 1.
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f1-ott-8-2121: ASIC1 mRNA expression in matched tumor and normal kidney samples.Notes: The expression level of ASIC1 mRNA was sixfold higher in the normal tissue than that in the tumor tissue. *Represents P<0.05 and n=8.Abbreviation: ASIC1, acid-sensing ion channel 1.

Mentions: ASIC1 expression in tumor tissue was compared with ASIC1 expression in matched normal tissue samples and normalized to the expression of the housekeeping gene GAPDH. The results of qPCR showed that the expression of ASIC1 mRNA was significantly decreased in CCRCC compared with matched normal tissues (Figure 1, n=8, P<0.05). Subsequently, we examined the expression of ASIC1 protein in these tissues using Western blot analysis. The results showed a band migrating at 55 kDa for ASIC1. Densitometric analysis showed that ASIC1 protein expression was significantly decreased in the CCRCC tissues compared with matched normal tissue (Figure 2, n=8, P<0.05).


Alteration of ASIC1 expression in clear cell renal cell carcinoma.

Li Y, Xu G, Huang K, Wang J, Zhang J, Liu J, Wang Z, Chen G - Onco Targets Ther (2015)

ASIC1 mRNA expression in matched tumor and normal kidney samples.Notes: The expression level of ASIC1 mRNA was sixfold higher in the normal tissue than that in the tumor tissue. *Represents P<0.05 and n=8.Abbreviation: ASIC1, acid-sensing ion channel 1.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4542551&req=5

f1-ott-8-2121: ASIC1 mRNA expression in matched tumor and normal kidney samples.Notes: The expression level of ASIC1 mRNA was sixfold higher in the normal tissue than that in the tumor tissue. *Represents P<0.05 and n=8.Abbreviation: ASIC1, acid-sensing ion channel 1.
Mentions: ASIC1 expression in tumor tissue was compared with ASIC1 expression in matched normal tissue samples and normalized to the expression of the housekeeping gene GAPDH. The results of qPCR showed that the expression of ASIC1 mRNA was significantly decreased in CCRCC compared with matched normal tissues (Figure 1, n=8, P<0.05). Subsequently, we examined the expression of ASIC1 protein in these tissues using Western blot analysis. The results showed a band migrating at 55 kDa for ASIC1. Densitometric analysis showed that ASIC1 protein expression was significantly decreased in the CCRCC tissues compared with matched normal tissue (Figure 2, n=8, P<0.05).

Bottom Line: 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).

View Article: PubMed Central - PubMed

Affiliation: Department of Urology, Fudan University, Shanghai, People's Republic of China.

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).

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.

No MeSH data available.


Related in: MedlinePlus