Dopamine and cyclic‐AMP activated phosphoprotein Mr32kDa (DARPP‐32) is a central signalling protein in neurotransmission. Following DARPP‐32 phosphorylation by protein kinase A (PKA), DARPP‐32 becomes a potent protein phosphatase 1 (PP1) inhibitor. DARPP‐32 can itself inhibit PKA following DARPP‐32 phosphorylation by cyclin‐dependent kinase 5 (Cdk5). Increasing evidence indicates a role for DARPP‐32 and its associated signalling pathways in cancer; however, its role in ovarian cancer remains unclear. Using immunohistochemistry, expression of DARPP‐32, PP1 and Cdk5 was determined in a large cohort of primary tumours from ovarian cancer patients (n = 428, 445 and 434 respectively) to evaluate associations between clinical outcome and clinicopathological criteria. Low cytoplasmic and nuclear DARPP‐32 expression was associated with shorter patient overall survival and progression‐free survival (P  = .001, .001, .004 and .037 respectively). Low nuclear and cytoplasmic DARPP‐32 expression remained significantly associated with overall survival in multivariate Cox regression (P  = .045, hazard ratio (HR) = 0.734, 95% confidence interval (CI) = 0.542‐0.993 and P  = .001, HR = 0.494, 95% CI = 0.325‐0.749, respectively). High cytoplasmic and nuclear PP1 expression was associated with shorter patient overall survival and high cytoplasmic PP1 expression with shorter progression‐free survival (P  = .005, .033, and .037, respectively). High Cdk5 expression was associated with shorter progression‐free survival (P  = .006). These data suggest a role for DARPP‐32 and associated signalling kinases as prognostic markers with clinical utility in ovarian cancer.

中文翻译：

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多巴胺和 cAMP 调节的磷蛋白 32kDa (DARPP-32)、蛋白磷酸酶-1 和细胞周期蛋白依赖性激酶 5 在卵巢癌中的表达。

多巴胺和环 AMP 激活的磷蛋白 Mr32kDa (DARPP-32) 是神经传递中的中枢信号蛋白。在 DARPP-32 被蛋白激酶 A (PKA) 磷酸化后，DARPP-32 成为一种有效的蛋白磷酸酶 1 (PP1) 抑制剂。在 DARPP-32 被细胞周期蛋白依赖性激酶 5 (Cdk5) 磷酸化后，DARPP-32 本身可以抑制 PKA。越来越多的证据表明 DARPP-32 及其相关信号通路在癌症中的作用；然而，其在卵巢癌中的作用仍不清楚。使用免疫组织化学，在来自卵巢癌患者（n = 428、445 和 434）的一大群原发性肿瘤中测定 DARPP-32、PP1 和 Cdk5 的表达，以评估临床结果和临床病理标准之间的关联。P  = .001、.001、.004 和 .037）。在多变量 Cox 回归中，低核和细胞质 DARPP-32 表达仍然与总生存期显着相关（P  = .045，风险比 (HR) = 0.734，95% 置信区间 (CI) = 0.542-0.993 和P  = .001，HR = 0.494, 95% CI = 0.325-0.749，分别）。高细胞质和细胞核 PP1 表达与较短的患者总生存期和高细胞质 PP1 表达与较短的无进展生存期相关（分别为P  = .005、.033 和 .037）。Cdk5 高表达与较短的无进展生存期相关（P = .006）。这些数据表明 DARPP-32 和相关信号激酶作为具有临床实用性的卵巢癌预后标志物的作用。