Liu Weisi, Yang Yuanfeng, Liu Yidong, Liu Haiou, Zhang Weijuan, Xu Le, Zhu Yu, Xu Jiejie
Key Laboratory of Glycoconjugate Research, MOH, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Shanghai Medical College of Fudan University, Shanghai, P.R. China.
Department of Urology, Zhongshan Hospital, Shanghai Medical College of Fudan University, Shanghai, P.R. China.
Urol Oncol. 2015 May;33(5):205.e13-21. doi: 10.1016/j.urolonc.2015.01.024. Epub 2015 Mar 2.
p21-Activated kinase 4 (PAK4), a serine/threonine kinase implicated in the cytoskeleton organization to orchestrate cell morphology, adhesion, and motility, is associated with angiogenesis and vessel branching, which are important events in the progression of clear cell renal cell carcinoma (ccRCC). We investigated the effect of PAK4 expression on recurrence and survival among patients with nonmetastatic ccRCC following surgery.
PAK4 expression was assessed, using immunohistochemistry, in 376 patients with nonmetastatic ccRCC after nephrectomy, where data of 187 patients were obtained from 2013 to 2014 and of 189 patients were obtained from 2008. Kaplan-Meier and Cox regression analyses were used to associate PAK4 expression with overall survival and recurrence-free survival.
Overall, 41.2% and 36.5% of specimens exhibited high PAK4 expression in 2 cohorts. Patients with high PAK4 expression were prone to possess high Fuhrman grade and tumor necrosis. Moreover, high PAK4 intensity was significantly associated with poor overall survival and recurrence-free survival. PAK4 expression remained an independent adverse prognosticator after adjusting for other well-established factors. Furthermore, in subgroups stratified by Fuhrman grade or T category, patients with high PAK4 intensity had an increased risk of recurrence and death. After adjusting for age, high PAK4 expression was an adverse prognostic marker in subgroup of low Fuhrman grade and in subgroup of early T category.
PAK4 expression is an independent adverse prognostic biomarker for recurrence and survival among patients with low-risk ccRCC after nephrectomy.
p21激活激酶4（PAK4）是一种丝氨酸/苏氨酸激酶，参与细胞骨架组织以协调细胞形态、黏附和运动，与血管生成和血管分支相关，而血管生成和血管分支是透明细胞肾细胞癌（ccRCC）进展中的重要事件。我们研究了PAK4表达对非转移性ccRCC患者术后复发和生存的影响。
采用免疫组织化学方法评估376例肾切除术后非转移性ccRCC患者的PAK4表达，其中187例患者的数据于2013年至2014年获得，189例患者的数据于2008年获得。采用Kaplan-Meier和Cox回归分析将PAK4表达与总生存和无复发生存相关联。
总体而言，在2个队列中，分别有41.2%和36.5%的标本显示PAK4高表达。PAK4高表达的患者更容易具有高Fuhrman分级和肿瘤坏死。此外，PAK4高表达强度与较差的总生存和无复发生存显著相关。在调整其他已确立的因素后，PAK4表达仍然是一个独立的不良预后指标。此外，在按Fuhrman分级或T分期分层的亚组中，PAK4高表达强度的患者复发和死亡风险增加。在调整年龄后，PAK4高表达在低Fuhrman分级亚组和早期T分期亚组中是一个不良预后标志物。
PAK4表达是肾切除术后低风险ccRCC患者复发和生存的独立不良预后生物标志物。
