Affiliations: [a] Department of Urology, Drum Tower Hospital, Medical School of Nanjing University, Institute of Urology, Nanjing University, Nanjing, Jiangsu, China | [b] Department of Urology, Peking University Third Hospital, Beijing, China | [c] Department of Pathology, Drum Tower Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China
Correspondence:
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Corresponding authors: Hongqian Guo and Xiaozhi Zhao, Department of Urology, Drum Tower Hospital, Medical School of Nanjing University, Institute of Urology, Nanjing University, Nanjing, Jiangsu, China. E-mail: dr.ghq@nju.edu.cnanddr.zxz@hotmail.com.
Note: [1] These authors contributed equally to this study.
Abstract: Postoperative recurrence for papillary renal cell carcinoma (PRCC) remains a tough problem in clinic. Previous studies have shown that general control nonderepressible kinase 2 (GCN2) was critically involved in tumour development. However, its function and clinical significance in renal cancer remain unknown. In this study, we investigated the role of GCN2 in PRCC. GCN2 silencing suppressed the viability and proliferation, promoted apoptosis of renal cancer cells. We found that the protein level of GCN2 was increased in PRCC tissues. Immunohistochemistry was performed in 84 patients with PRCC to explore the association of GCN2 level with clinical significance. High GCN2 protein level was observed to be significantly correlated with adverse clinicopathological parameters, such as larger tumor size, higher TNM stage, higher Fuhurman Grade, and lymph node metastasis. We evaluated patient outcomes according to various clinical parameters as well as GCN2 expression by Kaplan-Meier curves. Multivariate analysis revealed that GCN2 overexpression can be a predictive factor correlated with reduced OS and PFS of postoperative PRCC patients. Collectively, GCN2 is potentially to play crucial roles in PRCC progression, and its overexpression may be used to predict poor prognosis and promising therapeutic strategy for PRCC patients.
