| Autor: |
Lai SW; Division of Hematology/Oncology, Department of Internal Medicine, Tri-service General Hospital, National Defense Medical Center, Taipei, Taiwan., Weng PW; Department of Orthopaedics, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.; Department of Orthopaedics, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan.; Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei, Taiwan., Yadav VK; Department of Medical Research, Taipei Medical University Shuang-Ho Hospital, Taipei, Taiwan., Pikatan NW; Department of Medical Research, Taipei Medical University Shuang-Ho Hospital, Taipei, Taiwan., Yeh CT; Department of Medical Research, Taipei Medical University Shuang-Ho Hospital, Taipei, Taiwan.; Continuing Education Program of Food Biotechnology Applications, College of Science and Engineering, National Taitung University, Taitung, Taiwan., Hsieh MS; Department of Dentistry, Taipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan.; School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei City, Taiwan., Chou CL; Division of Nephrology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.; Taipei Medical University-Research Center of Urology and Kidney, Taipei Medical University, Taipei, Taiwan.; Division of Nephrology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei, Taiwan.; Division of Nephrology, Department of Internal Medicine, Hsin Kuo Min Hospital, Taipei Medical University, Taoyuan City, Taiwan. |
| Abstrakt: |
Renal cell carcinoma (RCC) is the predominant form of malignant kidney cancer. Sunitinib, a primary treatment for advanced, inoperable, recurrent, or metastatic RCC, has shown effectiveness in some patients but is increasingly limited by drug resistance. Recently identified cuproptosis, a copper-ion-dependent form of programmed cell death, holds promise in combating cancer, particularly drug-resistant types. However, its effectiveness in treating drug resistant RCC remains to be determined. Exploring cuproptosis's regulatory mechanisms could enhance RCC treatment strategies. Our analysis of data from the GEO and TCGA databases showed that the cuproptosis-related gene DBT is markedly under expressed in RCC tissues, correlating with worse prognosis and disease progression. In our study, we investigated copper CRGs in ccRCC, noting substantial expression differences, particularly in advanced-stage tumors. We established a connection between CRG expression levels and patient survival, positioning CRGs as potential therapeutic targets for ccRCC. In drug resistant RCC cases, we found distinct expression patterns for DBT and GLS CRGs, linked to treatment resistance. Our experiments demonstrated that increasing DBT expression significantly reduces RCC cell growth and spread, underscoring its potential as a therapeutic target. This research sheds new light on the role of CRGs in ccRCC and their impact on drug resistance. |
