Department of Urology, New York Presbyterian Hospital, Joan and Sanford I. Weill Medical College of Cornell University, New York, NY.
Department of Urology, New York Presbyterian Hospital, Joan and Sanford I. Weill Medical College of Cornell University, New York, NY; Institute for Computational Biomedicine, Joan and Sanford I. Weill Medical College of Cornell University, New York, NY.
Urol Oncol. 2020 May;38(5):418-422. doi: 10.1016/j.urolonc.2020.02.011. Epub 2020 Mar 17.
Speckle-type POZ protein (SPOP) mutation defines one of the dominant prostate cancer genomic subtypes, yet the impact of this mutation on clinical prognosis is unknown.
We defined SPOP mutation status either by DNA sequencing or by transcriptional signature in a pooled retrospective multi-institutional cohort, the Decipher retrospective cohort, the Decipher Genomics Resource Information Database prospective cohort, and The Cancer Genome Atlas. Kaplan-Meier survival analysis and multivariable Cox models were used to assess the independent impact of SPOP mutation on survival, biochemical recurrence and time to metastasis. The Decipher retrospective cohort was also used to assess the impact of the addition of SPOP mutation status to a model predicting adverse pathology at prostatectomy which was then validated in the Decipher prospective cohort.
A fixed-effect model incorporating results from multivariable Cox regression including 5,811 subjects demonstrated that SPOP mutation was associated with a lower rate of adverse pathology at radical prostatectomy (odds ratios 0.57, 95% confidence interval 0.34-0.93), independent of preoperative prostate-specific antigen, age, and pathologic Gleason score. SPOP was not associated with biochemical recurrence, metastasis-free survival, or cancer-specific survival independent of pathologic information. The addition of SPOP status to prognostic models reclassified a large proportion of patients with the mutation (55%) into a favorable risk group when used to predict adverse pathology.
While the clinical utility of delineating any single molecular alteration in prostate cancer remains unclear, these results illustrates the importance of genomic subtypes in prostate cancer behavior and potential role in prognostic tools.
斑点型 POZ 蛋白（SPOP）突变定义了其中一个主要的前列腺癌基因组亚型，但这种突变对临床预后的影响尚不清楚。
我们通过 DNA 测序或转录特征在一个回顾性多机构队列（Decipher 回顾性队列）、Decipher 基因组资源信息数据库前瞻性队列和癌症基因组图谱中定义 SPOP 突变状态。Kaplan-Meier 生存分析和多变量 Cox 模型用于评估 SPOP 突变对生存、生化复发和转移时间的独立影响。Decipher 回顾性队列还用于评估在预测前列腺切除术不良病理的模型中添加 SPOP 突变状态的影响，然后在 Decipher 前瞻性队列中进行验证。
一个包含 5811 名受试者的多变量 Cox 回归固定效应模型表明，SPOP 突变与前列腺癌根治性切除术时不良病理的发生率较低相关（比值比 0.57，95%置信区间 0.34-0.93），独立于术前前列腺特异性抗原、年龄和病理 Gleason 评分。SPOP 与生化复发、无转移生存或癌症特异性生存无关，独立于病理信息。当用于预测不良病理时，将 SPOP 状态添加到预后模型中可以将大部分突变患者（55%）重新分类为有利风险组。
虽然在前列腺癌中描述任何单一分子改变的临床应用尚不清楚，但这些结果说明了基因组亚型在前列腺癌行为中的重要性及其在预后工具中的潜在作用。
