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Development and validation of a prognostic model incorporating tumor thrombus grading for nonmetastatic clear cell renal cell carcinoma with tumor thrombus: A multicohort study

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单位: [1]Department of Urology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China [2]Department of Urology, Jinling Hospital, Jinling School of Clinical Medicine, Nanjing Medical University, Nanjing, Jiangsu, China [3]Department of Pathology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China [4]Department of Health Statistics, Naval Medical University, Shanghai, China [5]Department of Urology, Changhai Hospital, Naval Medical University, Shanghai, China [6]Department of Urology, Qilu Hospital of Shandong University, Jinan, Shandong, China [7]Department of Pathomorphology, Medical University of Gdańsk, Gdańsk, Poland [8]Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University Shanghai, Shanghai, China [9]Department of Pathology, Changhai Hospital,NavalMedical University, Shanghai, China [10]Department of Urology, Daping Hospital, Army Medical University, Chongqing, China [11]Department of Pathology, Qilu Hospital of Shandong University, Jinan, Shandong, China [12]Department of Urology,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,Hubei,China [13]Department of Pathology, Drum Tower Hospital, Clinical School of Medical College, Nanjing University, Nanjing, Jiangsu, China [14]Department of Urology, Drum Tower Hospital, Clinical School of Medical College, Nanjing University, Nanjing, Jiangsu, China [15]Department of Pathology, Zhongda Hospital, Southeast University, Nanjing, Jiangsu, China [16]Department of Urology, Zhongda Hospital, Southeast University, Nanjing, Jiangsu, China [17]Department of Urology, Xiangya Hospital, Central South University, Changsha, Hunan, China [18]Department of Urology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China [19]Department of Urology, Huashan Hospital, Fudan University, Shanghai, China [20]Department of Urology, Affiliated Yantai Yuhuangding Hospital, Qingdao University, Yantai, Shandong, China [21]Department of Pathology, Affiliated Yantai Yuhuangding Hospital, Qingdao University, Yantai, Shandong, China [22]Department of Urology, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China [23]Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China [24]Department of Urology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China [25]Department of Urology, Urology Research Institute, The First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian, China [26]Department of Urology, Anhui Provincial Hospital, The First Hospital of the University of Science and Technology of China, Hefei, Anhui, China [27]Department of Urology, Shanghai East Hospital, Tongji University, Shanghai, China [28]Department of Pathology, Shanghai East Hospital, Tongji University, Shanghai, China [29]Department of Urology, Xijing Hospital, Fourth Military Medical University, Xi’an, Shanxi, China [30]Department of Pathology, Xijing Hospital, Fourth Military Medical University, Xi’an, Shanxi, China [31]Department of Medical Oncology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China [32]Clinic of General, Oncological and Functional Urology, Medical University of Warsaw,Warsaw, Poland
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关键词: clear cell renal cell carcinoma pathological grading prognostic model risk stratification

摘要:
There is significant variability with respect to the prognosis of nonmetastatic clear cell renal cell carcinoma (ccRCC) patients with venous tumor thrombus (VTT). By applying multiregion whole-exome sequencing on normal-tumor-thrombus-metastasis quadruples from 33 ccRCC patients, we showed that metastases were mainly seeded by VTT (81.8%) rather than primary tumors (PTs). A total of 706 nonmetastatic ccRCC patients with VTT from three independent cohorts were included in this study. C-index analysis revealed that pathological grading of VTT outperformed other indicators in risk assessment (OS: 0.663 versus 0.501-0.610, 0.667 versus 0.544-0.651, and 0.719 versus 0.511-0.700 for Training, China-Validation, and Poland-Validation cohorts, respectively). We constructed a risk predicting model, TT-GPS score, based on four independent variables: VTT height, VTT grading, perinephric fat invasion, and sarcomatoid differentiation in PT. The TT-GPS score displayed better discriminatory ability (OS, c-index: 0.706-0.840, AUC: 0.788-0.874; DFS, c-index: 0.691-0.717, AUC: 0.771-0.789) than previously reported models in risk assessment. In conclusion, we identified for the first-time pathological grading of VTT as an unheeded prognostic factor. By incorporating VTT grading, the TT-GPS score is a promising prognostic tool in predicting the survival of nonmetastatic ccRCC patients with VTT.© 2023 The Authors. MedComm published by Sichuan International Medical Exchange & Promotion Association (SCIMEA) and John Wiley & Sons Australia, Ltd.

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大类 | 1 区 医学
小类 | 1 区 医学:研究与实验
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Q1 MEDICINE, RESEARCH & EXPERIMENTAL

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第一作者单位: [1]Department of Urology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China [2]Department of Urology, Jinling Hospital, Jinling School of Clinical Medicine, Nanjing Medical University, Nanjing, Jiangsu, China [*1]Department of Urology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, 305 East Zhongshan Road, Nanjing 210000, China
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通讯机构: [1]Department of Urology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China [2]Department of Urology, Jinling Hospital, Jinling School of Clinical Medicine, Nanjing Medical University, Nanjing, Jiangsu, China [5]Department of Urology, Changhai Hospital, Naval Medical University, Shanghai, China [*1]Department of Urology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, 305 East Zhongshan Road, Nanjing 210000, China [*2]Department of Urology, Changhai Hospital, Naval Medical University, 168 Changhai Road, Shanghai 200433, China
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