Chao Wang1,2,3, TianYu Hong1, Yuning Wang1, Guang Peng4,5,6, Yongwei Yu7, Jing Zhang1, Dong Zhuo8, Jingcun Zheng9, Xiaojing Ma10, Xingang Cui11,12. 1. Department of Urinary Surgery, Gongli Hospital, The Second Military Medical University (Naval Medical University), 219 Miaopu Road, Shanghai, 200135, China. 2. Shanghai Heath Commission Key Lab of Artificial Intelligence (AI)-Based Management of Inflammation and Chronic Diseases, Gongli Hospital, The Second Military Medical University (Naval Medical University), 219 Miaopu Road, Shanghai, 200135, China. 3. Department of Urology, The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, 29 Xinglong Road, Changzhou, 213000, Jiangsu, China. 4. Department of Urinary Surgery, The Third Affiliated Hospital of Second Military Medical University (Eastern Hepatobiliary Surgery Hospital), 700 North Moyu Road, Shanghai, 201805, China. 5. Department of Urology, Joint Logistic Support Force No. 925 Hospital of PLA, 67 Yellow River Road, Guiyang, 550009, Guizhou, China. 6. Department of Orthopedic, Joint Logistic Support Force No. 925 Hospital of PLA, 67 Yellow River Road, Guiyang, 550009, Guizhou, China. 7. Department of Pathology, Changhai Hospital, Second Military Medical University (Naval Medical University), 168 Changhai Road, Shanghai, 200438, China. 8. Department of Microbiology and Immunology, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY, 10065-4805, USA. whzhuo2008@sina.com. 9. Department of Urinary Surgery, Gongli Hospital, The Second Military Medical University (Naval Medical University), 219 Miaopu Road, Shanghai, 200135, China. zhengjingc@sina.com. 10. Department of Urology, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), No. 2 West Zheshan RD, Wuhu, Anhui, 241000, China. xim2002@med.cornell.edu. 11. Department of Urinary Surgery, Gongli Hospital, The Second Military Medical University (Naval Medical University), 219 Miaopu Road, Shanghai, 200135, China. cuixingang@smmu.edu.cn. 12. Department of Urinary Surgery, The Third Affiliated Hospital of Second Military Medical University (Eastern Hepatobiliary Surgery Hospital), 700 North Moyu Road, Shanghai, 201805, China. cuixingang@smmu.edu.cn.
Abstract
PURPOSE: Identification of reliable postoperative indicators for accurately evaluating prognosis of clear cell renal cell carcinoma (ccRCC) patients remains an important clinical issue. This study determined the prognostic value of UBR5 expression in ccRCC patients by combining with CD163+ tumor-associated macrophages (TAMs) and the established clinical parameters. METHODS: The expression of UBR5 was analyzed in ccRCC patients from TCGA databases. A total of 310 ccRCC patients were randomly divided into the training and validation cohorts at a 3:2 or 1:1 ratio, and immunohistochemistry (IHC) and statistical analyses were performed to examine the prognostic value of UBR5 and CD163+ TAMs. RESULTS: UBR5 expression was commonly downregulated in human ccRCC specimens, which was associated with TNM stage, SSIGN, WHO/ISUP Grading and poor prognosis of ccRCC patients. In addition, UBR5 expression was negatively correlated with CD163 expression (a TAM marker) in ccRCC tissues, and combining expressions of UBR5 and CD163 better predicted worse overall survival and progression-free survival of ccRCC patients. Even after multivariable adjustment, UBR5, CD163, TNM stage and SSIGN appeared to be independent risk factors. By time-dependent c-index analysis, the integration of intratumoral UBR5 and CD163 achieved higher c-index value than UBR5, CD163, TNM stage or SSIGN alone in predicting ccRCC patients' prognosis. Moreover, the incorporation of both UBR5 and CD163 into the clinical indicators TNM stage or SSIGN exhibited highest c-index value. CONCLUSIONS: Integrating intratumoral UBR5 and CD163+ TAMs with the current clinical parameters achieves better accuracy in predicting ccRCC patients' postoperative prognosis.
PURPOSE: Identification of reliable postoperative indicators for accurately evaluating prognosis of clear cell renal cell carcinoma (ccRCC) patients remains an important clinical issue. This study determined the prognostic value of UBR5 expression in ccRCC patients by combining with CD163+ tumor-associated macrophages (TAMs) and the established clinical parameters. METHODS: The expression of UBR5 was analyzed in ccRCC patients from TCGA databases. A total of 310 ccRCC patients were randomly divided into the training and validation cohorts at a 3:2 or 1:1 ratio, and immunohistochemistry (IHC) and statistical analyses were performed to examine the prognostic value of UBR5 and CD163+ TAMs. RESULTS:UBR5 expression was commonly downregulated in human ccRCC specimens, which was associated with TNM stage, SSIGN, WHO/ISUP Grading and poor prognosis of ccRCC patients. In addition, UBR5 expression was negatively correlated with CD163 expression (a TAM marker) in ccRCC tissues, and combining expressions of UBR5 and CD163 better predicted worse overall survival and progression-free survival of ccRCC patients. Even after multivariable adjustment, UBR5, CD163, TNM stage and SSIGN appeared to be independent risk factors. By time-dependent c-index analysis, the integration of intratumoral UBR5 and CD163 achieved higher c-index value than UBR5, CD163, TNM stage or SSIGN alone in predicting ccRCC patients' prognosis. Moreover, the incorporation of both UBR5 and CD163 into the clinical indicators TNM stage or SSIGN exhibited highest c-index value. CONCLUSIONS: Integrating intratumoral UBR5 and CD163+ TAMs with the current clinical parameters achieves better accuracy in predicting ccRCC patients' postoperative prognosis.
Authors: Kimberley Jones; Frank Vari; Colm Keane; Pauline Crooks; Jamie P Nourse; Louise A Seymour; David Gottlieb; David Ritchie; Devinder Gill; Maher K Gandhi Journal: Clin Cancer Res Date: 2012-12-05 Impact factor: 12.531
Authors: Piotr M Wierzbicki; Jakub Klacz; Anna Kotulak-Chrzaszcz; Agata Wronska; Marcin Stanislawowski; Agnieszka Rybarczyk; Aleksandra Ludziejewska; Zbigniew Kmiec; Marcin Matuszewski Journal: Int J Oncol Date: 2019-06-25 Impact factor: 5.650