RT Journal Article
SR Electronic
T1 Reduced anoctamin 7 (ANO7) expression is a strong and independent predictor of poor prognosis in prostate cancer
JF Cancer Biology and Medicine
JO Cancer Biol Med
FD China Anti-Cancer Association
SP 245
OP 255
DO 10.20892/j.issn.2095-3941.2019.0324
VO 18
IS 1
A1 Andreas Marx
A1 Lena Koopmann
A1 Doris Höflmayer
A1 Franziska Büscheck
A1 Claudia Hube-Magg
A1 Stefan Steurer
A1 Till Eichenauer
A1 Till S. Clauditz
A1 Waldemar Wilczak
A1 Ronald Simon
A1 Guido Sauter
A1 Jakob R. Izbicki
A1 Hartwig Huland
A1 Hans Heinzer
A1 Markus Graefen
A1 Alexander Haese
A1 Thorsten Schlomm
A1 Christian Bernreuther
A1 Patrick Lebok
A1 Sarah Bonk
YR 2021
UL http://www.cancerbiomed.org/content/18/1/245.abstract
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.