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Reduced anoctamin 7 (ANO7) expression is a strong and independent predictor of poor prognosis in prostate cancer
OBJECTIVE: Anoctamin 7 (ANO7) is a calcium(2+)-dependent chloride ion channel protein. Its expression is restricted to prostate epithelial cells. The exact function is unknown. This study aimed to analyze ANO7 expression and its clinical significance in prostate cancer (PCa). METHODS: ANO7 expressio...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Compuscript
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7877177/ https://www.ncbi.nlm.nih.gov/pubmed/33628598 http://dx.doi.org/10.20892/j.issn.2095-3941.2019.0324 |
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author | Marx, Andreas Koopmann, Lena Höflmayer, Doris Büscheck, Franziska Hube-Magg, Claudia Steurer, Stefan Eichenauer, Till Clauditz, Till S. Wilczak, Waldemar Simon, Ronald Sauter, Guido Izbicki, Jakob R. Huland, Hartwig Heinzer, Hans Graefen, Markus Haese, Alexander Schlomm, Thorsten Bernreuther, Christian Lebok, Patrick Bonk, Sarah |
author_facet | Marx, Andreas Koopmann, Lena Höflmayer, Doris Büscheck, Franziska Hube-Magg, Claudia Steurer, Stefan Eichenauer, Till Clauditz, Till S. Wilczak, Waldemar Simon, Ronald Sauter, Guido Izbicki, Jakob R. Huland, Hartwig Heinzer, Hans Graefen, Markus Haese, Alexander Schlomm, Thorsten Bernreuther, Christian Lebok, Patrick Bonk, Sarah |
author_sort | Marx, Andreas |
collection | PubMed |
description | OBJECTIVE: Anoctamin 7 (ANO7) is a calcium(2+)-dependent chloride ion channel protein. Its expression is restricted to prostate epithelial cells. The exact function is unknown. This study aimed to analyze ANO7 expression and its clinical significance in prostate cancer (PCa). METHODS: ANO7 expression was assessed by immunohistochemistry in 17,747 clinical PCa specimens. RESULTS: ANO7 was strongly expressed in normal prostate glandular cells but often less abundant in cancer cells. ANO7 staining was interpretable in 13,594 cancer tissues and considered strong in 34.4%, moderate in 48.7%, weak in 9.3%, and negative in 7.6%. Reduced staining was tightly linked to adverse tumor features [high classical and quantitative Gleason grade, lymph node metastasis, advanced tumor stage, high Ki67 labeling index, positive surgical margin, and early biochemical recurrence (P < 0.0001 each)]. The univariate Cox hazard ratio for prostate-specific antigen (PSA) recurrence after prostatectomy in patients with negative vs. strong ANO7 expression was 2.98 (95% confidence interval 2.61–3.38). The prognostic impact was independent of established pre- or postoperatively available parameters (P < 0.0001). Analysis of annotated molecular data showed that low ANO7 expression was linked to TMPRSS2:ERG fusions (P < 0.0001), elevated androgen receptor expression (P < 0.0001), as well as presence of 9 of 11 chromosomal deletions (P < 0.05 each). A particularly strong association of low ANO7 expression with phosphatase and tensin homolog (PTEN) deletion may indicate a functional relationship with the PTEN/AKT pathway. CONCLUSIONS: These data identify reduced ANO7 protein expression as a strong and independent predictor of poor prognosis in PCa. ANO7 measurement, either alone or in combination, might provide clinically useful prognostic information in PCa. |
format | Online Article Text |
id | pubmed-7877177 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Compuscript |
record_format | MEDLINE/PubMed |
spelling | pubmed-78771772021-02-23 Reduced anoctamin 7 (ANO7) expression is a strong and independent predictor of poor prognosis in prostate cancer Marx, Andreas Koopmann, Lena Höflmayer, Doris Büscheck, Franziska Hube-Magg, Claudia Steurer, Stefan Eichenauer, Till Clauditz, Till S. Wilczak, Waldemar Simon, Ronald Sauter, Guido Izbicki, Jakob R. Huland, Hartwig Heinzer, Hans Graefen, Markus Haese, Alexander Schlomm, Thorsten Bernreuther, Christian Lebok, Patrick Bonk, Sarah Cancer Biol Med Original Article OBJECTIVE: Anoctamin 7 (ANO7) is a calcium(2+)-dependent chloride ion channel protein. Its expression is restricted to prostate epithelial cells. The exact function is unknown. This study aimed to analyze ANO7 expression and its clinical significance in prostate cancer (PCa). METHODS: ANO7 expression was assessed by immunohistochemistry in 17,747 clinical PCa specimens. RESULTS: ANO7 was strongly expressed in normal prostate glandular cells but often less abundant in cancer cells. ANO7 staining was interpretable in 13,594 cancer tissues and considered strong in 34.4%, moderate in 48.7%, weak in 9.3%, and negative in 7.6%. Reduced staining was tightly linked to adverse tumor features [high classical and quantitative Gleason grade, lymph node metastasis, advanced tumor stage, high Ki67 labeling index, positive surgical margin, and early biochemical recurrence (P < 0.0001 each)]. The univariate Cox hazard ratio for prostate-specific antigen (PSA) recurrence after prostatectomy in patients with negative vs. strong ANO7 expression was 2.98 (95% confidence interval 2.61–3.38). The prognostic impact was independent of established pre- or postoperatively available parameters (P < 0.0001). Analysis of annotated molecular data showed that low ANO7 expression was linked to TMPRSS2:ERG fusions (P < 0.0001), elevated androgen receptor expression (P < 0.0001), as well as presence of 9 of 11 chromosomal deletions (P < 0.05 each). A particularly strong association of low ANO7 expression with phosphatase and tensin homolog (PTEN) deletion may indicate a functional relationship with the PTEN/AKT pathway. CONCLUSIONS: These data identify reduced ANO7 protein expression as a strong and independent predictor of poor prognosis in PCa. ANO7 measurement, either alone or in combination, might provide clinically useful prognostic information in PCa. Compuscript 2021-02-15 2021-02-15 /pmc/articles/PMC7877177/ /pubmed/33628598 http://dx.doi.org/10.20892/j.issn.2095-3941.2019.0324 Text en Copyright: © 2021, Cancer Biology & Medicine https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY) 4.0 (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Original Article Marx, Andreas Koopmann, Lena Höflmayer, Doris Büscheck, Franziska Hube-Magg, Claudia Steurer, Stefan Eichenauer, Till Clauditz, Till S. Wilczak, Waldemar Simon, Ronald Sauter, Guido Izbicki, Jakob R. Huland, Hartwig Heinzer, Hans Graefen, Markus Haese, Alexander Schlomm, Thorsten Bernreuther, Christian Lebok, Patrick Bonk, Sarah Reduced anoctamin 7 (ANO7) expression is a strong and independent predictor of poor prognosis in prostate cancer |
title | Reduced anoctamin 7 (ANO7) expression is a strong and independent predictor of poor prognosis in prostate cancer |
title_full | Reduced anoctamin 7 (ANO7) expression is a strong and independent predictor of poor prognosis in prostate cancer |
title_fullStr | Reduced anoctamin 7 (ANO7) expression is a strong and independent predictor of poor prognosis in prostate cancer |
title_full_unstemmed | Reduced anoctamin 7 (ANO7) expression is a strong and independent predictor of poor prognosis in prostate cancer |
title_short | Reduced anoctamin 7 (ANO7) expression is a strong and independent predictor of poor prognosis in prostate cancer |
title_sort | reduced anoctamin 7 (ano7) expression is a strong and independent predictor of poor prognosis in prostate cancer |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7877177/ https://www.ncbi.nlm.nih.gov/pubmed/33628598 http://dx.doi.org/10.20892/j.issn.2095-3941.2019.0324 |
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