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Reduced anoctamin 7(ANO7) expression is a strong and independent predictor of poor prognosis in prostate cancer

Cancer Biology & Medicine 2021年第1期18卷 245-255页

作者： Andreas Marx Lena Koopmann Doris Hoflmayer 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 Institute of Pathology Klinikum FurthFurth 90766Germany Institute of Pathology University Medical Center Hamburg-EppendorfHamburg 20246Germany Department of Urology University Medical Center Hamburg-EppendorfHamburg 20246Germany General Visceral and Thoracic Surgery Department and ClinicUniversity Medical Center Hamburg-EppendorfHamburg 20246Germany Martini-Clinic Prostate Cancer CenterUniversity Medical Center Hamburg-EppendorfHamburg 20246Germany Department of Urology Charité-Universit?tsmedizin BerlinBerlin 10117Germany

Objective:Anoctamin 7(ANO7)is a calcium2+-dependent chloride ion channel *** expression is restricted to prostate epithelial *** exact function is *** 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 ***:ANO7 was strongly expressed in normal prostate glandular cells but often less abundant in cancer ***7 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 *** 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 ***:These data identify reduced ANO7 protein expression as a strong and independent predictor of poor prognosis in ***7 measurement,either alone or in combination,might provide clinically useful prognostic information in PCa.

关键词： ANO7 immunohistochemistry prognosis prostate cancer

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