James Buchanan Brady Urological Institute, Johns Hopkins Hospital, Baltimore, Maryland.
GenomeDx Biosciences, Vancouver, British Columbia, Canada.
J Urol. 2016 Nov;196(5):1436-1444. doi: 10.1016/j.juro.2016.05.092. Epub 2016 May 27.
Prostate cancer is clinically and molecularly heterogeneous. We determined the prognosis of men with ERG-ETS fusions and SPINK1 over expression.
Men were identified with intermediate or high risk localized prostate cancer treated with radical prostatectomy and no therapy before metastasis. A case-cohort design sampled a cohort (262) enriched with metastasis from the entire cohort and a cohort (213) enriched with metastasis from patients with biochemical recurrence. We analyzed transcriptomic profiles and subtyped tumors as m-ERG, m-ETS, m-SPINK1 or Triple Negative (m-ERG/m-ETS/m-SPINK1), and multivariable logistic regression analyses, Kaplan-Meier and multivariable Cox models were used to evaluate subtypes as predictors of clinical outcomes.
Overall 36%, 13%, 11% and 40% of prostate cancer was classified as m-ERG, m-ETS, m-SPINK1 and Triple Negative, respectively. Univariable analysis demonstrated that m-SPINK1 tumors were more common in African-American men (OR 5, 95% CI 1.6-16) but less commonly associated with positive surgical margins (OR 0.16, 95% CI 0.03-0.69) compared to the m-ERG group. Compared to the Triple Negative group, m-SPINK1 showed similar associations with race and surgical margins in univariable and multivariable analyses across the entire cohort. Survival analyses did not show significant differences among m-ERG, m-ETS and Triple Negative cases. m-SPINK1 independently predicted prostate cancer specific mortality after metastasis (HR 2.48, 95% CI 0.96-6.4) and biochemical recurrence (HR 3, 95% CI 1.1-8).
SPINK1 over expression is associated with prostate cancer specific mortality in at risk men with biochemical and clinical recurrence after prostatectomy. ERG-ETS alterations are not prognostic for outcome.
前列腺癌在临床上和分子上具有异质性。我们确定了 ERG-ETS 融合和 SPINK1 过表达的男性患者的预后。
我们鉴定了接受根治性前列腺切除术且在转移前未接受任何治疗的局部高危前列腺癌男性患者。采用病例队列设计,从整个队列中富集转移病例(262 例)和从生化复发患者中富集转移病例(213 例)构建队列。我们分析了转录组谱,并将肿瘤分为 m-ERG、m-ETS、m-SPINK1 或三重阴性(m-ERG/m-ETS/m-SPINK1),并进行多变量逻辑回归分析、Kaplan-Meier 和多变量 Cox 模型分析,评估亚型作为临床结局的预测因子。
总体而言,前列腺癌的 36%、13%、11%和 40%分别被归类为 m-ERG、m-ETS、m-SPINK1 和三重阴性。单变量分析表明,m-SPINK1 肿瘤在非裔美国男性中更为常见(OR 5,95%CI 1.6-16),但与阳性切缘的相关性较低(OR 0.16,95%CI 0.03-0.69),与 m-ERG 组相比。与三重阴性组相比,m-SPINK1 在整个队列的单变量和多变量分析中与种族和手术切缘的相关性相似。生存分析显示 m-ERG、m-ETS 和三重阴性病例之间无显著差异。m-SPINK1 独立预测前列腺癌特异性死亡率(HR 2.48,95%CI 0.96-6.4)和生化复发(HR 3,95%CI 1.1-8)。
在接受根治性前列腺切除术且在生化和临床复发后具有风险的男性中,SPINK1 过表达与前列腺癌特异性死亡率相关。ERG-ETS 改变与预后无关。