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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 immunohistochemistry.Notes: (A) Normal renal tissue with prominent ASIC1 expression. (B–D) ASIC1 expression in CCRCC with high- (B), intermediate- (C), and low- (D) staining density, respectively.Abbreviations: ASIC1, acid-sensing ion channel 1; CCRCC, clear cell renal cell carcinoma.
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f3-ott-8-2121: ASIC1 immunohistochemistry.Notes: (A) Normal renal tissue with prominent ASIC1 expression. (B–D) ASIC1 expression in CCRCC with high- (B), intermediate- (C), and low- (D) staining density, respectively.Abbreviations: ASIC1, acid-sensing ion channel 1; CCRCC, clear cell renal cell carcinoma.

Mentions: To analyze ASIC1 as a valuable diagnostic tissue marker for CCRCC, we performed tissue-microarray based on immunohistochemical analysis and performed a statistical analysis of the immunohistochemical ASIC1 protein expression. CCRCC tissues and matched adjacent normal tissues from 75 patients were included in this study. The clinicopathological characteristics of the study population and the ASIC1 staining intensity in different groups are depicted in Table 1. The mean age of patients was 57.5 (range 34–82). Figure 3 shows representative examples of the expression of ASIC1 in human CCRCC and normal renal tissues. Of the 75 renal carcinomas, 30 cases (40.0%) were weakly positive, 14 cases (18.7%) showed a moderate ASIC1 expression, and 31 cases (41.3%) were strongly positive. Of adjacent normal tissues, 20 cases (26.7%) were weakly positive, 15 cases (20%) showed a moderate ASIC1 expression, and 40 cases (53.3%) were strongly positive. CCRCC tissues showed a downregulation of ASIC1 in 68% of the cases. 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=0.0004). 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). In Spearman correlations, ASIC1 expression did not correlate to tumor stage (CC =0.168, P=0.149) and age of patients (CC =−0.147, P=0.688) but showed a positive correlation to higher tumor grades (CC =0.270, P=0.018).


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 immunohistochemistry.Notes: (A) Normal renal tissue with prominent ASIC1 expression. (B–D) ASIC1 expression in CCRCC with high- (B), intermediate- (C), and low- (D) staining density, respectively.Abbreviations: ASIC1, acid-sensing ion channel 1; CCRCC, clear cell renal cell carcinoma.
© Copyright Policy
Related In: Results  -  Collection

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

f3-ott-8-2121: ASIC1 immunohistochemistry.Notes: (A) Normal renal tissue with prominent ASIC1 expression. (B–D) ASIC1 expression in CCRCC with high- (B), intermediate- (C), and low- (D) staining density, respectively.Abbreviations: ASIC1, acid-sensing ion channel 1; CCRCC, clear cell renal cell carcinoma.
Mentions: To analyze ASIC1 as a valuable diagnostic tissue marker for CCRCC, we performed tissue-microarray based on immunohistochemical analysis and performed a statistical analysis of the immunohistochemical ASIC1 protein expression. CCRCC tissues and matched adjacent normal tissues from 75 patients were included in this study. The clinicopathological characteristics of the study population and the ASIC1 staining intensity in different groups are depicted in Table 1. The mean age of patients was 57.5 (range 34–82). Figure 3 shows representative examples of the expression of ASIC1 in human CCRCC and normal renal tissues. Of the 75 renal carcinomas, 30 cases (40.0%) were weakly positive, 14 cases (18.7%) showed a moderate ASIC1 expression, and 31 cases (41.3%) were strongly positive. Of adjacent normal tissues, 20 cases (26.7%) were weakly positive, 15 cases (20%) showed a moderate ASIC1 expression, and 40 cases (53.3%) were strongly positive. CCRCC tissues showed a downregulation of ASIC1 in 68% of the cases. 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=0.0004). 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). In Spearman correlations, ASIC1 expression did not correlate to tumor stage (CC =0.168, P=0.149) and age of patients (CC =−0.147, P=0.688) but showed a positive correlation to higher tumor grades (CC =0.270, P=0.018).

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