First Department of Pathology, Medical School, Laiko Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece.
Hum Pathol. 2011 Oct;42(10):1545-53. doi: 10.1016/j.humpath.2010.12.018. Epub 2011 Apr 14.
Replication protein A is a single-stranded DNA-binding protein that is required for the stabilization of single-stranded DNA and identified in replication foci where members of cyclin-dependent kinases-cyclin complexes are also present. In this study, we investigated the expression of replication protein A1 and replication protein A2 subunits of replication protein A protein in correlation with cyclins D2 and D3 and nuclear factor κB expression and assessed their prognostic significance in 66 patients with astrocytomas. Statistically significant positive associations emerged between (a) replication protein A1 and replication protein A2 protein expression (P < .0001); (b) cyclins D2 and D3 expression (P < .0001); (c) replication protein A1, replication protein A2, and cyclins D2 and D3 expression and histologic grade (P = .0001 in all correlations); (d) replication protein A1 and cyclin D2 or D3 expression (P < .0001 in both relationships); and (e) replication protein A2 and cyclin D2 or D3 expression (P < .0001 in both relationships). Nuclear factor κB1/p50 expression was positively correlated with replication protein A1, replication protein A2, and cyclins D2 and D3 expression, although these relationships failed to retain statistical significance when they were adjusted for histologic grade. Replication protein A2 expression seemed to independently affect survival in grade IV (P = .005) as well as in the entire cohort (P = .006). None of the molecules under study seemed to influence survival in lower grades (II/III), either by univariate or by multivariate analysis. In conclusion, replication protein A1, replication protein A2, and cyclins D2 and D3 seem to have a parallel role in the promotion of cell cycle in astrocytic tumors being implicated in the malignant progression of these neoplasms. Moreover, replication protein A2 protein seems to be a useful prognostic indicator in patients with astrocytomas.
复制蛋白 A 是一种单链 DNA 结合蛋白，对于稳定单链 DNA 是必需的，并在复制焦点中被鉴定出来，在那里，细胞周期蛋白依赖性激酶-细胞周期蛋白复合物的成员也存在。在这项研究中，我们调查了复制蛋白 A 蛋白的复制蛋白 A1 和复制蛋白 A2 亚单位与细胞周期蛋白 D2 和 D3 的表达之间的相关性，并评估了它们在 66 例星形细胞瘤患者中的预后意义。（a）复制蛋白 A1 和复制蛋白 A2 蛋白表达之间存在显著的正相关关系（P <.0001）；（b）细胞周期蛋白 D2 和 D3 表达之间存在显著的正相关关系（P <.0001）；（c）复制蛋白 A1、复制蛋白 A2、细胞周期蛋白 D2 和 D3 表达与组织学分级之间存在显著的正相关关系（所有相关性中 P =.0001）；（d）复制蛋白 A1 与细胞周期蛋白 D2 或 D3 表达之间存在显著的正相关关系（在这两种关系中 P <.0001）；（e）复制蛋白 A2 与细胞周期蛋白 D2 或 D3 表达之间存在显著的正相关关系（在这两种关系中 P <.0001）。核因子 κB1/p50 的表达与复制蛋白 A1、复制蛋白 A2 和细胞周期蛋白 D2 和 D3 的表达呈正相关，尽管当它们被组织学分级调整时，这些关系未能保留统计学意义。复制蛋白 A2 表达似乎独立地影响 IV 级（P =.005）以及整个队列（P =.006）的生存。在较低的分级（II/III）中，没有一种研究的分子通过单变量或多变量分析影响生存。总之，复制蛋白 A1、复制蛋白 A2 和细胞周期蛋白 D2 和 D3 似乎在星形细胞瘤中促进细胞周期方面具有平行作用，参与了这些肿瘤的恶性进展。此外，复制蛋白 A2 蛋白似乎是星形细胞瘤患者的一个有用的预后指标。
