Prognostic Significance of p21-activated Kinase 6 Expression in Patients with Clear Cell Renal Cell Carcinoma

To investigate prognostic values of intratumoral p21-activated kinase 6 (PAK6) expression in patients with clear cell renal cell carcinoma (ccRCC).

Immunohistochemistry in tissue microarray was used to evaluate the expression of PAK6 in 104 patients who had undergone nephrectomy at Zhongshan Hospital of Fudan University. Prognostic value and clinical outcomes were evaluated.

Intratumoral PAK6 expression was significantly lower than nontumoral tissues (P < 0.001). Moreover, low expression of PAK6 was associated with unfavorable overall survival (OS) (P = 0.001) and recurrence-free survival (RFS) (P = 0.001). In the subgroup of patients with tumor, node, metastasis classification system (TNM) stage I + II disease, those with low expression of PAK6 were prone to have poor OS (P = 0.014) and RFS (P = 0.037). Intratumoral PAK6 low expression was correlated with tumor size (P = 0.001) and TNM stage (P = 0.006), and was identified as an independent prognostic factor for OS (hazard ratio 4.109, P = 0.002) and RFS (hazard ratio 3.175, P = 0.002). Use of an extended TNM staging system with intratumoral PAK6 expression showed a better prognostic value for OS [area under the receiver operating characteristic curve (AUC) 0.790, P = 0.022] and RFS (AUC 0.769, P = 0.040). The c-index of a Cox-based model combined with Eastern Cooperative Oncology Group performance status, TNM stage, Fuhrman grade, and PAK6 was 0.83 for OS and 0.80 for RFS.

Intratumoral PAK6 could be a potential prognosticator for OS and RFS in ccRCC patients after nephrectomy. Further external validation and functional analysis should be pursued to assess its potential prognostic and therapeutic values for ccRCC patients.