p21‐activated kinase 1 predicts recurrence and survival in patients with non‐metastatic clear cell renal cell carcinoma

Abstract

Objectives: To estimate the impact of p21-activated kinase 1 expression on recurrence and survival of patients with non-metastatic clear cell renal cell carcinoma after surgical resection. Methods: We retrospectively enrolled 254 patients (187 in the training cohort and 67 in the validation cohort) with non-metastatic clear cell renal cell carcinoma undergoing nephrectomy at a single institution. Clinicopathological features, overall survival and recurrence-free survival were recorded. p21-activated kinase 1 intensities were assessed by immunohistochemistry of patients' specimens. The Kaplan-Meier method was applied to compare survival curves. Cox regression models were used to analyze the impact of prognostic factors on overall survival and recurrence-free survival. The concordance index was calculated to assess predictive accuracy. Results: In both cohorts, elevated p21-activated kinase 1 expression in tumor tissues positively correlated with advanced T stage and Fuhrman grade. High p21-activated kinase 1 expression indicated poor survival and early recurrence of patients with non-metastatic clear cell renal cell carcinoma, especially with early T1-2 stage disease. After backward elimination, p21-activated kinase 1 expression was identified as an independent adverse prognostic factor for survival and recurrence. The predictive accuracy of the traditional University of California Integrated Staging System and Mayo Clinic stage, size, grade and necrosis prognostic models was improved when p21-activated kinase 1 expression was added. Conclusions: Elevated expression of p21-activated kinase 1 seems to be an independent adverse prognostic biomarker for recurrence and survival in patients with non-metastatic clear cell renal cell carcinoma after nephrectomy.

Tumor necrosis as a prognostic variable for the clinical outcome in patients with renal cell carcinoma: a systematic review and meta-analysis

“…Although several pathologic parameters, including lymphatic vessel invasion [45], tumor fat invasion [26] and primary tumor size [43], provide independent prognostic information, the likely outcome for an individual patient remains uncertain. The TNM stage and Fuhrman grade system are the most widely used approaches for RCC; however, there have been many recent suggestions for modifications based on survival trends in large case series [46]. Additionally, RCC is a highly heterogeneous disease with different clinical presentations and characteristics that remain somewhat unpredictable [47].…”

Overexpression of PAK1 Correlates with Aberrant Expression of EMT Markers and Poor Prognosis in Non-Small Cell Lung Cancer

“…PAK1 is over-expressed in various malignancies such as ovarian, breast, lung, and bladder cancers, and is closely associated with tumor invasion20, 21. The PAK1 expression level is positively correlated with tumor progression, metastases, and poor prognosis of specific carcinomas20, 22, 23. The inhibition of PAK1 expression or disruption of its function may significantly inhibit cancer cell proliferation and metastasis18, 19, 24, 25.…”

Editorial Comment to p21‐activated kinase 1 predicts recurrence and survival in patients with non‐metastatic clear cell renal cell carcinoma

“…In this issue of the International Journal of Urology , Zhu et al . reported the results of a single institutional retrospective study of East Asian patients with localized clear cell RCC that was designed to determine the outcomes of patients with this disease and the prognostic factors . Zhu et al .…”

“…examined p21‐activated kinase 1 (PAK1), which is a serine/threonine kinase that orchestrates cytoskeletal remodeling and cell motility. PAK1 has been shown to play various oncogenic roles in promoting cell proliferation, regulating apoptosis and accelerating mitotic abnormalities, all of which result in tumor formation and invasiveness . They showed that high PAK1 expression indicated poor survival and early disease recurrence in patients with non‐metastatic clear cell RCC, particularly those with early T1–2 stage disease.…”

“…The prognostic factor of patients after local surgery for non‐metastatic RCC is an important issue for future research. As described in the study by Zhu et al ., none of the trials carried out during the cytokine era showed clinical benefit in the adjuvant setting . However, based on the efficacies in the metastatic setting, various trials using tyrosine kinase inhibitors have been proposed as adjuvant therapy for high‐risk non‐metastatic RCC after surgery with radical intent.…”