Department of Urology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing 100730, China
Xinhua Qiao
National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China
Ting Xie
National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China
Wenbin Cai
Tianjin Key Laboratory of Metabolic Diseases, Collaborative Innovation Center of Tianjin for Medical Epigenetics, Center for Cardiovascular Diseases, Research Center of Basic Medical Sciences, Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin 300070, China
Xu Zhang
Tianjin Key Laboratory of Metabolic Diseases, Collaborative Innovation Center of Tianjin for Medical Epigenetics, Center for Cardiovascular Diseases, Research Center of Basic Medical Sciences, Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin 300070, China
Chang Chen
National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China
Yaoguang Zhang
Department of Urology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing 100730, China
Clear cell renal cell carcinoma (ccRCC) is a malignant tumor originating from proximal tubular epithelial cells, and despite extensive research efforts, its redox homeostasis characteristics and protein S-nitrosylation (or S-nitrosation) (SNO) modification remain largely undefined. This serves as a reminder that the aforementioned features demand a comprehensive inspection. We collected tumor samples and paracancerous normal samples from five patients with early-stage ccRCC (T1N0M0) for proteomic, SNO-proteome, and redox-targeted metabolic analyses. The localization and functional properties of SNO proteins in ccRCC tumors and paracancerous normal tissues were elucidated for the first time. Several highly useful ccRCC-associated SNO proteins were further identified. Metabolic reprogramming, redox homeostasis reprogramming, and tumorigenic alterations are the three major characteristics of early-stage ccRCC. Peroxidative damage caused by rapid proliferation coupled with an increased redox buffering capacity and the antioxidant pool is a major mode of redox homeostasis reprogramming. NADPH and NADP+, which were identified from redox species, are both effective biomarkers and promising therapeutic targets. According to our findings, SNO protein signatures and redox homeostasis reprogramming are valuable for understanding the pathogenesis of ccRCC and identifying novel topics that should be seriously considered for the diagnosis and precise therapy of ccRCC.
