Gankyrin is a novel biomarker for disease progression and prognosis of patients with renal cell carcinomaResearch in context
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. In this study, we assessed the expression and prognostic value of gankyrin in RCC patients. Methods: The expression of ganky...
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Elsevier
2019-01-01
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Series: | EBioMedicine |
Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396418305826 |
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Article |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Chao Wang Yan Li Chuan-min Chu Xiang-min Zhang Jie Ma Hai Huang Yu-ning Wang Tian-yu Hong Jing Zhang Xiu-wu Pan Jing-cun Zheng Ning Jiang Chuan-yi Hu Xiaojing Ma Ying-hao Sun Xin-gang Cui |
spellingShingle |
Chao Wang Yan Li Chuan-min Chu Xiang-min Zhang Jie Ma Hai Huang Yu-ning Wang Tian-yu Hong Jing Zhang Xiu-wu Pan Jing-cun Zheng Ning Jiang Chuan-yi Hu Xiaojing Ma Ying-hao Sun Xin-gang Cui Gankyrin is a novel biomarker for disease progression and prognosis of patients with renal cell carcinomaResearch in context EBioMedicine |
author_facet |
Chao Wang Yan Li Chuan-min Chu Xiang-min Zhang Jie Ma Hai Huang Yu-ning Wang Tian-yu Hong Jing Zhang Xiu-wu Pan Jing-cun Zheng Ning Jiang Chuan-yi Hu Xiaojing Ma Ying-hao Sun Xin-gang Cui |
author_sort |
Chao Wang |
title |
Gankyrin is a novel biomarker for disease progression and prognosis of patients with renal cell carcinomaResearch in context |
title_short |
Gankyrin is a novel biomarker for disease progression and prognosis of patients with renal cell carcinomaResearch in context |
title_full |
Gankyrin is a novel biomarker for disease progression and prognosis of patients with renal cell carcinomaResearch in context |
title_fullStr |
Gankyrin is a novel biomarker for disease progression and prognosis of patients with renal cell carcinomaResearch in context |
title_full_unstemmed |
Gankyrin is a novel biomarker for disease progression and prognosis of patients with renal cell carcinomaResearch in context |
title_sort |
gankyrin is a novel biomarker for disease progression and prognosis of patients with renal cell carcinomaresearch in context |
publisher |
Elsevier |
series |
EBioMedicine |
issn |
2352-3964 |
publishDate |
2019-01-01 |
description |
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. In this study, we assessed the expression and prognostic value of gankyrin in RCC patients. Methods: The expression of gankyrin was examined in public databases and validated in specimens from two independent centers. The clinical practice and disease correlation of gankyrin in RCC were evaluated in RCC patients, various cell lines and an orthotopic RCC model. Findings: Upregulation of gankyrin expression in RCC was corroborated in two independent cohorts. High gankyrin expression positively associated with disease progression and metastasis of RCC patients. A positive correlation between gankyrin and sunitinib-resistance was also observed in RCC cell lines and in an orthotopic RCC model. 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. Time-dependent AUC and Harrell's c-index analysis presented that the incorporation of the gankyrin classifier into the current clinical prognostic parameters such as TNM stage, Fuhrman nuclear grade or SSIGN score achieved a greater accuracy than without it in predicting prognosis of RCC patients. All results were confirmed in randomized training and validation sets from the two patient cohorts. 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 patient management. Fund: National Natural Science Foundation of China (No. 81773154, 81772747 and 81301861), Medical Discipline Construction Project of Pudong New Area Commission of Health and Family Planning (PWYgf2018-03), the Shanghai Medical Guidance (Chinese and Western Medicine) Science and Technology Support Project (No. 17411960200), Outstanding Leaders Training Program of Pudong Health Bureau of Shanghai (No. PWR12016-05) Keywords: Renal cell carcinoma, Gankyrin, Prognosis, Disease progression |
url |
http://www.sciencedirect.com/science/article/pii/S2352396418305826 |
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doaj-a6d47c85d1dd4022a3505470146e2bab2020-11-25T01:44:33ZengElsevierEBioMedicine2352-39642019-01-0139255264Gankyrin is a novel biomarker for disease progression and prognosis of patients with renal cell carcinomaResearch in contextChao Wang0Yan Li1Chuan-min Chu2Xiang-min Zhang3Jie Ma4Hai Huang5Yu-ning Wang6Tian-yu Hong7Jing Zhang8Xiu-wu Pan9Jing-cun Zheng10Ning Jiang11Chuan-yi Hu12Xiaojing Ma13Ying-hao Sun14Xin-gang Cui15Department of Urinary Surgery, Gongli Hospital, Second Military Medical University (Naval Medical University), 219 Miaopu Road, Shanghai 200135, China; Department of Urology, Changhai Hospital, Second Military Medical University (Naval Medical University), 168 Changhai Road, Shanghai 200438, ChinaNingxia Medical University, Yinchuan, Ningxia 750004, China; Department of Urinary Surgery, Gongli Hospital, Second Military Medical University (Naval Medical University), 219 Miaopu Road, Shanghai 200135, ChinaDepartment of Urinary Surgery, The Third Affiliated Hospital of Second Military Medical University (Eastern Hepatobiliary Surgery Hospital), 700 North Moyu Road, Shanghai 201805, China; Department of Urinary Surgery, Gongli Hospital, Second Military Medical University (Naval Medical University), 219 Miaopu Road, Shanghai 200135, ChinaDepartment of Urinary Surgery, Gongli Hospital, Second Military Medical University (Naval Medical University), 219 Miaopu Road, Shanghai 200135, ChinaDepartment of Urinary Surgery, Gongli Hospital, Second Military Medical University (Naval Medical University), 219 Miaopu Road, Shanghai 200135, ChinaDepartment of Urinary Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197 Ruijin Road No. 2, Shanghai 200025, ChinaDepartment of Urinary Surgery, Gongli Hospital, Second Military Medical University (Naval Medical University), 219 Miaopu Road, Shanghai 200135, China; Ningxia Medical University, Yinchuan, Ningxia 750004, ChinaDepartment of Urinary Surgery, Gongli Hospital, Second Military Medical University (Naval Medical University), 219 Miaopu Road, Shanghai 200135, China; Ningxia Medical University, Yinchuan, Ningxia 750004, ChinaDepartment of Urinary Surgery, Gongli Hospital, Second Military Medical University (Naval Medical University), 219 Miaopu Road, Shanghai 200135, ChinaDepartment of Urinary Surgery, The Third Affiliated Hospital of Second Military Medical University (Eastern Hepatobiliary Surgery Hospital), 700 North Moyu Road, Shanghai 201805, ChinaDepartment of Urinary Surgery, Gongli Hospital, Second Military Medical University (Naval Medical University), 219 Miaopu Road, Shanghai 200135, ChinaDepartment of Urinary Surgery, Gongli Hospital, Second Military Medical University (Naval Medical University), 219 Miaopu Road, Shanghai 200135, ChinaDepartment of Urinary Surgery, Gongli Hospital, Second Military Medical University (Naval Medical University), 219 Miaopu Road, Shanghai 200135, China; Correspondence to: C.Y. Hu, Department of Urinary Surgery, Gongli Hospital, Second Military Medical University, 219 Miaopu Road, Shanghai 200135, China.Department of Microbiology and Immunology, Weill Medical College of Cornell University, 1300 York Avenue, New York 10065-4805, NY, United States.; Correspondence to: X. Ma: Department of Microbiology and Immunology, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10065-4805, United StatesDepartment of Urology, Changhai Hospital, Second Military Medical University (Naval Medical University), 168 Changhai Road, Shanghai 200438, China; Correspondence to: Y.H. Sun, Department of Urology, Changhai Hospital, Second Military Medical University, 168 Changhai Road, Shanghai 200438, China.Department of Urinary Surgery, Gongli Hospital, Second Military Medical University (Naval Medical University), 219 Miaopu Road, Shanghai 200135, China; Department of Urinary Surgery, The Third Affiliated Hospital of Second Military Medical University (Eastern Hepatobiliary Surgery Hospital), 700 North Moyu Road, Shanghai 201805, China; Correspondence to: X.G. Cui, Department of Urinary Surgery, Gongli Hospital, Second Military Medical University, 219 Miaopu Road, Shanghai 200135, China.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. In this study, we assessed the expression and prognostic value of gankyrin in RCC patients. Methods: The expression of gankyrin was examined in public databases and validated in specimens from two independent centers. The clinical practice and disease correlation of gankyrin in RCC were evaluated in RCC patients, various cell lines and an orthotopic RCC model. Findings: Upregulation of gankyrin expression in RCC was corroborated in two independent cohorts. High gankyrin expression positively associated with disease progression and metastasis of RCC patients. A positive correlation between gankyrin and sunitinib-resistance was also observed in RCC cell lines and in an orthotopic RCC model. 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. Time-dependent AUC and Harrell's c-index analysis presented that the incorporation of the gankyrin classifier into the current clinical prognostic parameters such as TNM stage, Fuhrman nuclear grade or SSIGN score achieved a greater accuracy than without it in predicting prognosis of RCC patients. All results were confirmed in randomized training and validation sets from the two patient cohorts. 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 patient management. Fund: National Natural Science Foundation of China (No. 81773154, 81772747 and 81301861), Medical Discipline Construction Project of Pudong New Area Commission of Health and Family Planning (PWYgf2018-03), the Shanghai Medical Guidance (Chinese and Western Medicine) Science and Technology Support Project (No. 17411960200), Outstanding Leaders Training Program of Pudong Health Bureau of Shanghai (No. PWR12016-05) Keywords: Renal cell carcinoma, Gankyrin, Prognosis, Disease progressionhttp://www.sciencedirect.com/science/article/pii/S2352396418305826 |