p21-Activated kinase 4 predicts early recurrence and poor survival in patients with nonmetastatic clear cell renal cell carcinoma

Backgroundp21-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.MethodsPAK4 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.ResultsOverall, 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.ConclusionPAK4 expression is an independent adverse prognostic biomarker for recurrence and survival among patients with low-risk ccRCC after nephrectomy.