Weisi Liu1, Yuanfeng Yang2, Yidong Liu1, Haiou Liu1, Weijuan Zhang3, Le Xu2, Yu Zhu4, Jiejie Xu5. 1. 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. 2. Department of Urology, Zhongshan Hospital, Shanghai Medical College of Fudan University, Shanghai, P.R. China. 3. Department of Immunology, School of Basic Medical Sciences, Shanghai Medical College of Fudan University, Shanghai, P.R. China. 4. Department of Urology, Ninth People׳s Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, P.R. China. 5. 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. Electronic address: jjxufdu@fudan.edu.cn.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: PAK4 expression is an independent adverse prognostic biomarker for recurrence and survival among patients with low-risk ccRCC after nephrectomy.
BACKGROUND: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. METHODS: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. RESULTS: 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. CONCLUSION:PAK4 expression is an independent adverse prognostic biomarker for recurrence and survival among patients with low-risk ccRCC after nephrectomy.
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