Gankyrin is a Novel Biomarker for Disease Progression and Prognosis of Patients with Renal Cell Carcinoma

Abstract

Background: In the clinic, how to stratify renal cell carcinoma (RCC) patients with different risks and to accurately predict their prognostic outcome remains a crucial issue. There is a lack of relevant and reliable biomarkers. In this study, we examined the expression and prognostic value of gankyrin in RCC patients. Methods: The expression of gankyrin in RCC specimens was examined in public database, and validated in specimens in our institution. The clinical practice of gankyrin (or combined with other current clinical parameters) in RCC patients was evaluated in two independent cohorts of RCC patients. Findings: Analyses based on public TCGA, GEO and ONCOMINE databases revealed that gankyrin expression was up-regulated in RCC specimens, which was also confirmed in RCC patients from two independent cohorts. In addition, high gankyrin expression positively associated with disease progression, metastasis and sunitinib-resistance of RCC patients. Kaplan-Meier analysis revealed that patients with higher gankyrin expression presented worse prognosis of RCC patients in the two cohorts. Gankyrin served as an independent prognostic factor for RCC patients even after multivariable adjustment by clinical variables. Furthermore, time-dependent AUC and Harrell's c-index analysis both presented that the incorporation of the gankyrin classifier into the current clinical prognostic parameters such as TNM stage, Furman nuclear grade or SSIGN score achieves a greater accuracy than without it in predicting prognosis of RCC patients. All these results were confirmed in randomized training and validation sets from the above two cohorts of patients. Interpretation: Gankyrin can serve as a reliable biomarker for disease progression and for prognosis of RCC patients. Combining gankyrin with the current clinical parameters may help clinical management for RCC patients. Funding Statement: This work was supported by National Natural Science Foundation of China (No. 81773154, 81772747 and 81301861), Shanghai Natural Science Foundation of China (No. 13ZR1450700), the Shanghai Medical Guidance (Chinese and Western Medicine) Science and Technology Support Project (No. 17411960200) and Outstanding Leaders Training Program of Pudong Health Bureau of Shanghai (No.PWR12016-05). Declaration of Interests: The authors declare no potential conflicts of interest. Ethics Approval Statement: The present study was followed the reporting recommendations for tumor marker prognostic studies (REMARK), and was approved by the institutional ethical review boards from all hospitals, and written informed consent was obtained from all patients.