Reduced anoctamin 7 (ANO7) expression is a strong and independent predictor of poor prognosis in prostate cancer
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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.
in: CANCER BIOL MED, Jahrgang 18, Nr. 1, 15.02.2021, S. 245-255.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Reduced anoctamin 7 (ANO7) expression is a strong and independent predictor of poor prognosis in prostate cancer
AU - Marx, Andreas
AU - Koopmann, Lena
AU - Höflmayer, Doris
AU - Büscheck, Franziska
AU - Hube-Magg, Claudia
AU - Steurer, Stefan
AU - Eichenauer, Till
AU - Clauditz, Till S
AU - Wilczak, Waldemar
AU - Simon, Ronald
AU - Sauter, Guido
AU - Izbicki, Jakob R
AU - Huland, Hartwig
AU - Heinzer, Hans
AU - Graefen, Markus
AU - Haese, Alexander
AU - Schlomm, Thorsten
AU - Bernreuther, Christian
AU - Lebok, Patrick
AU - Bonk, Sarah
N1 - Copyright: © 2021, Cancer Biology & Medicine.
PY - 2021/2/15
Y1 - 2021/2/15
N2 - Objective: Anoctamin 7 (ANO7) is a calcium2+-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.
AB - Objective: Anoctamin 7 (ANO7) is a calcium2+-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.
U2 - 10.20892/j.issn.2095-3941.2019.0324
DO - 10.20892/j.issn.2095-3941.2019.0324
M3 - SCORING: Journal article
C2 - 33628598
VL - 18
SP - 245
EP - 255
JO - CANCER BIOL MED
JF - CANCER BIOL MED
SN - 2095-3941
IS - 1
ER -