Boolean analysis identifies CD38 as a biomarker of aggressive localized prostate cancer.
Boolean analysis identifies CD38 as a biomarker of aggressive localized prostate cancer.
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DOI：
10.18632/oncotarget.23973
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发表时间：
2018-01-19
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影响因子：
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通讯作者：
Brooks, James D
中科院分区：
文献类型：
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作者：
Sahoo, Debashis;Wei, Wei;Brooks, James D
近30年前，血清前列腺特异性抗原（PSA）检测的引入与局部疾病的显著转变和前列腺癌死亡率的降低有关。认识到PSA检测导致了前列腺癌的过度诊断和过度治疗，对其价值产生了相当大的争议，并促使人们努力确定预后生物标志物，以区分需要治疗的患者和可以观察到的患者。最近的研究表明，癌症是异质性的，并形成肿瘤细胞群的层次结构。我们开发了一种使用布尔逻辑识别与雄激素信号传导相关的前列腺癌分化状态的方法。使用基因表达数据，我们确定了两个标记物，CD 38和ARG 2，将前列腺癌分为三种分化状态。与最高分化组（CD 38 + ARG 2+）相比，具有CD 38-、ARG 2-表达模式的癌症（对应于未分化状态）的10年无复发生存率显著较低。我们在单个机构（斯坦福大学; n = 234）和多机构（Canary; n = 1326）队列中对这两种标志物进行了免疫组织化学（IHC）染色。在斯坦福大学队列中对CD 38和ARG 2进行的IHC染色表明，CD 38和ARG 2的联合表达具有预后意义。在Canary队列中，单变量分析显示，免疫组化检测的低CD 38蛋白表达与无复发生存期（RFS）、精囊浸润（SVI）、包膜外浸润（ECE）显著相关。在多变量分析中，ARG 2和CD 38 IHC染色结果与RFS、总生存期或校正其他因素（包括SVI、ECE、Gleason评分、术前PSA和手术切缘）后的疾病特异性生存期无关。
The introduction of serum Prostate Specific Antigen (PSA) testing nearly 30 years ago has been associated with a significant shift towards localized disease and decreased deaths due to prostate cancer. Recognition that PSA testing has caused over diagnosis and over treatment of prostate cancer has generated considerable controversy over its value, and has spurred efforts to identify prognostic biomarkers to distinguish patients who need treatment from those that can be observed. Recent studies show that cancer is heterogeneous and forms a hierarchy of tumor cell populations. We developed a method of identifying prostate cancer differentiation states related to androgen signaling using Boolean logic. Using gene expression data, we identified two markers, CD38 and ARG2, that group prostate cancer into three differentiation states. Cancers with CD38-, ARG2- expression patterns, corresponding to an undifferentiated state, had significantly lower 10-year recurrence-free survival compared to the most differentiated group (CD38+ARG2+). We carried out immunohistochemical (IHC) staining for these two markers in a single institution (Stanford; n = 234) and multi-institution (Canary; n = 1326) cohorts. IHC staining for CD38 and ARG2 in the Stanford cohort demonstrated that combined expression of CD38 and ARG2 was prognostic. In the Canary cohort, low CD38 protein expression by IHC was significantly associated with recurrence-free survival (RFS), seminal vesicle invasion (SVI), extra-capsular extension (ECE) in univariable analysis. In multivariable analysis, ARG2 and CD38 IHC staining results were not independently associated with RFS, overall survival, or disease-specific survival after adjusting for other factors including SVI, ECE, Gleason score, pre-operative PSA, and surgical margins.