Reduced anoctamin 7 (ANO7) expression is a strong and independent predictor of poor prognosis in prostate cancer
Andreas H. Marx, Lena Koopmann, Doris Höflmayer, Franziska Büscheck, Claudia Hube‐Magg, Stefan Steurer, Till Eichenauer, Till S. Clauditz, Waldemar Wilczak, Ronald Simon, Guido Sauter, Jakob R. Izbicki, Hartwig Huland, Hans Heinzer, Markus Graefen, Alexander Haese, Thorsten Schlomm, Christian Bernreuther, Patrick Lebok, Sarah Bonk
Abstract
Objective: Anoctamin 7 (ANO7) is a calcium2+-dependent chloride ion channel protein. Its expression is restricted to prostateepithelial cells. The exact function is unknown. This study aimed to analyze ANO7 expression and its clinical significance in prostatecancer (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 stainingwas 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)]. Theunivariate Cox hazard ratio for prostate-specific antigen (PSA) recurrence after prostatectomy in patients with negative vs. strongANO7 expression was 2.98 (95% confidence interval 2.61–3.38). The prognostic impact was independent of established pre- orpostoperatively available parameters (P < 0.0001). Analysis of annotated molecular data showed that low ANO7 expression waslinked to TMPRSS2:ERG fusions (P < 0.0001), elevated androgen receptor expression (P < 0.0001), as well as presence of 9 of 11chromosomal deletions (P < 0.05 each). A particularly strong association of low ANO7 expression with phosphatase and tensinhomolog (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.