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Combining UBR5 and CD163+ tumor-associated macrophages better predicts prognosis of clear cell renal cell carcinoma patients

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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.

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Acknowledgements

This work was supported by the Top-level Clinical Discipline Project of Shanghai Pudong (PWYgf2018-03), National Natural Science Foundation of China (Nos. 81773154, 81772747, 81974391), Shanghai Natural Science Foundation (20ZR1449600), Pudong New Area Science and technology development fund special fund for people’s livelihood Research (medical and health) (PKJ2019-Y19), the Program of Shanghai Academic/Technology Research Leader (No. 19XD1405100), the Shanghai “Rising Stars of Medical Talent” Youth Development Program: Outstanding Youth Medical Talents (Xin-gang Cui), Meng Chao Talent Training Program-Cultivation of Leading Talents Reserve (Xin-gang Cui), and the Shanghai Medical Guidance (Chinese and Western Medicine) Science and Technology Support Project (No. 17411960200). We thank Dr. Aiping Zhang (Department of Urinary Surgery, Gongli Hospital, Shanghai, China) for her assistance in providing the clinical samples of ccRCC patients. We also thank Shanghai BioGenius biotech. Co., Ltd (China) for his BioGenius Cloud Computing Service and bioinformatics analysis.

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Author notes

  1. Chao Wang, TianYu Hong, Yuning Wang, Guang Peng, and Yongwei Yu contributed equally to the study.

Authors and Affiliations

  1. Department of Urinary Surgery, Gongli Hospital, The Second Military Medical University (Naval Medical University), 219 Miaopu Road, Shanghai, 200135, China

    Chao Wang, TianYu Hong, Yuning Wang, Jing Zhang, Jingcun Zheng & Xingang Cui

  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

    Chao Wang

  3. Department of Urology, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, 29 Xinglong Road, Changzhou, 213000, Jiangsu, China

    Chao Wang

  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

    Guang Peng & Xingang Cui

  5. Department of Urology, Joint Logistic Support Force No. 925 Hospital of PLA, 67 Yellow River Road, Guiyang, 550009, Guizhou, China

    Guang Peng

  6. Department of Orthopedic, Joint Logistic Support Force No. 925 Hospital of PLA, 67 Yellow River Road, Guiyang, 550009, Guizhou, China

    Guang Peng

  7. Department of Pathology, Changhai Hospital, Second Military Medical University (Naval Medical University), 168 Changhai Road, Shanghai, 200438, China

    Yongwei Yu

  8. 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

    Xiaojing Ma

  9. Department of Microbiology and Immunology, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY, 10065-4805, USA

    Dong Zhuo

Authors
  1. Chao Wang
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  2. TianYu Hong
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  3. Yuning Wang
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  4. Guang Peng
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  5. Yongwei Yu
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  6. Jing Zhang
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  7. Dong Zhuo
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  8. Jingcun Zheng
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  9. Xiaojing Ma
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  10. Xingang Cui
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Contributions

Chao Wang, Dong Zhuo, Jingcun Zheng, Xiaojing Ma and Xingang Cui designed the study; Chao Wang wrote the manuscript; Chao Wang, TianYu Hong, Guang Peng, Yuning Wang and Yongwei Yu analyzed the data, performed the experiments and statistical analysis; Jing Zhang provided the ccRCC patient samples; and Zhuo Dong, Jingcun Zheng, Xiaojing Ma and Xingang Cui supervised the study and reviewed the manuscript.

Corresponding authors

Correspondence to Dong Zhuo, Jingcun Zheng, Xiaojing Ma or Xingang Cui.

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All authors have no conflicts of interest to disclose. All authors have contributed significantly, and all authors are in agreement with the content of the manuscript.

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Wang, C., Hong, T., Wang, Y. et al. Combining UBR5 and CD163+ tumor-associated macrophages better predicts prognosis of clear cell renal cell carcinoma patients. Cancer Immunol Immunother 70, 2925–2935 (2021). https://doi.org/10.1007/s00262-021-02885-9

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  • DOI: https://doi.org/10.1007/s00262-021-02885-9

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