Previous studies have shown the prognostic value of PAK1 expression in different tumor patients, including nonmetastatic renal cell carcinoma. In this study, we explored the prognostic and drug predictive value of PAK1 expression in metastatic renal cell carcinoma (mRCC) patients treated with tyrosine kinase inhibitors (TKIs).
We retrospectively enrolled 138 mRCC patients treated with TKIs from a single institution from 2005 to 2014. Analyses were based on 111 patients who met our inclusion criteria. The validation set enrolled 538 RCC patients from The Cancer Genome Atlas Kidney Renal Clear Cell Carcinoma cohort (TCGA KIRC) between 1998 and 2013 in North America. PAK1 expression was assessed by immunohistochemistry (IHC) on tissue microarrays.
High PAK1 expression was associated with short overall survival (OS) (P < 0.001) and progression-free survival (PFS) (P = 0.008). Multivariate analyses further indicated that PAK1 expression was an independent prognostic factor for OS (hazard ratio 3.301 [95% confidence interval 2.579-10.899], P < 0.001) and PFS (hazard ratio 3.108 [95% confidence interval 1.795-5.381], P < 0.001). Subgroup analyses suggested that PAK1 was more significant in patients with the intermediate risk group of Heng risk criteria (OS, P = 0.004). Of note, patients treated with Sunitinib showed improved outcome in the low PAK1 subgroup (OS, P = 0.002; PFS, P = 0.013). Finally, relationship was found between PAK1 expression and natural killer cell-mediated cytotoxicity according to gene profile investigation.
High PAK1 expression predicted dismal prognosis in mRCC patients treated with TKIs. Besides, PAK1 was a potential predictor for TKIs treatments.
Urologic oncology. 2019 Dec 27 [Epub ahead of print]
Yang Qu, Zhiyuan Lin, Yu Qi, Yangyang Qi, Yifan Chen, Quan Zhou, Han Zeng, Zheng Liu, Zewei Wang, Jiajun Wang, Yuan Chang, Qi Bai, Yu Xia, Yiwei Wang, Yu Zhu, Le Xu, Lingli Chen, Peipei Zhang, Weijuan Zhang, Bo Dai, Li Liu, Jiejie Xu, Jianming Guo
Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China., Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, China., Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China., Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China., Department of Urology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China., Department of Urology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China., Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China., Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China., Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China. Electronic address: .