Loss of Expression of AZGP1 Is Associated With Worse Clinical Outcomes in a Multi-Institutional Radical Prostatectomy Cohort.
Loss of Expression of AZGP1 Is Associated With Worse Clinical Outcomes in a Multi-Institutional Radical Prostatectomy Cohort.
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DOI：
10.1002/pros.23225
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发表时间：
2016-11
期刊：
影响因子：
--
通讯作者：
Fazli L
中科院分区：
文献类型：
--
作者：
Brooks JD;Wei W;Pollack JR;West RB;Shin JH;Sunwoo JB;Hawley SJ;Auman H;Newcomb LF;Simko J;Hurtado-Coll A;Troyer DA;Carroll PR;Gleave ME;Lin DW;Nelson PS;Thompson IM;True LD;McKenney JK;Feng Z;Fazli L
考虑到前列腺癌侵袭性的临床测量中固有的不确定性，需要经过临床验证的组织生物标记物。我们测试了免疫组织化学检测的α-2-糖蛋白1和锌结合蛋白(AZGP1)水平以及RNA原位杂交(RISH)检测的RNA表达是否独立于临床和病理参数预测前列腺癌根治术后复发。AZGP1、IHC和RISH在一个大型多机构组织微阵列资源上进行，包括1275名男性，平均随访5年。用Kappa分析评估IHC和RISH表达水平之间的关系。用卡方检验和Wilcoxon秩和检验来检验与临床和病理参数的相关性。用单变量和多变量Cox比例风险模型和Log-ranch检验评估与预后的关系。单因素分析显示，AZGP1蛋白表达缺失或弱表达与前列腺癌根治术后无复发生存期(RFS)、疾病特异性生存期和总生存期相关。多变量分析显示，AZGP1蛋白表达与术前血清PSA水平、手术切缘状况、精囊侵犯、包膜外侵犯和Gleason评分一起预测RFS。同样，在单变量和多变量分析中，RISH的AZGP1RNA表达缺失或低表达预示着前列腺切除术后RFS的恶化。在我们设计严谨的大型验证队列中，AZGP1表达缺失可独立于临床和病理变量预测前列腺癌根治术后的RFS。
Given the uncertainties inherent in clinical measures of prostate cancer aggressiveness, clinically validated tissue biomarkers are needed. We tested whether Alpha-2-Glycoprotein 1, Zinc-Binding (AZGP1) protein levels, measured by immunohistochemistry, and RNA expression, by RNA in situ hybridization (RISH), predict recurrence after radical prostatectomy independent of clinical and pathological parameters. AZGP1 IHC and RISH were performed on a large multi-institutional tissue microarray resource including 1275 men with 5 year median follow-up. The relationship between IHC and RISH expression levels was assessed using the Kappa analysis. Associations with clinical and pathological parameters were tested by the Chi-square test and the Wilcoxon rank sum test. Relationships with outcome were assessed with univariable and multivariable Cox proportional hazards models and the Log-rank test. Absent or weak expression of AZGP1 protein was associated with worse recurrence free survival (RFS), disease specific survival and overall survival after radical prostatectomy in univariable analysis. AZGP1 protein expression, along with pre-operative serum PSA levels, surgical margin status, seminal vesicle invasion, extracapsular extension and Gleason score predicted RFS on multivariable analysis. Similarly, absent or low AZGP1 RNA expression by RISH predicted worse RFS after prostatectomy in univariable and multivariable analysis. In our large, rigorously designed validation cohort, loss of AZGP1 expression predicts RFS after radical prostatectomy independent of clinical and pathological variables.
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