Combining UBR5 and CD163+ tumor-associated macrophages better predicts prognosis of clear cell renal cell carcinoma patients
Combining UBR5 and CD163+ tumor-associated macrophages better predicts prognosis of clear cell renal cell carcinoma patients
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DOI：
10.1007/s00262-021-02885-9
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发表时间：
2021-03
期刊：
影响因子：
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通讯作者：
Chao Wang;Tian-yu Hong;Yuning Wang;G. Peng;Yongwei Yu;Jing Zhang;Dong Zhuo;Jing-cun Zheng;Xiaojing Ma;X. Cui
中科院分区：
文献类型：
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作者：
Chao Wang;Tian-yu Hong;Yuning Wang;G. Peng;Yongwei Yu;Jing Zhang;Dong Zhuo;Jing-cun Zheng;Xiaojing Ma;X. Cui
目的寻找可靠的术后指标准确评估肾透明细胞癌（ccRCC）患者的预后仍然是一个重要的临床问题。本研究通过结合CD 163+肿瘤相关巨噬细胞（TAMs）和建立的临床参数确定了UBR 5表达在ccRCC患者中的预后价值。结果UBR 5在人肾细胞癌组织中表达普遍下调，且与肾细胞癌的TNM分期、SSGN、WHO/ISUP分级及预后不良相关。此外，在ccRCC组织中，UBR 5表达与CD 163表达（TAM标志物）呈负相关，UBR 5和CD 163的联合表达更好地预测了ccRCC患者的总生存期和无进展生存期。多因素校正后，UBR 5、CD 163、TNM分期和SSGN仍为独立危险因素。通过时间依赖性c指数分析，在预测ccRCC患者的预后方面，肿瘤内UBR 5和CD 163的整合比UBR 5、CD 163、TNM分期或SSIGN单独获得更高的c指数值。此外，UBR 5和CD 163的掺入到临床指标TNM分期或SSIGN表现出最高的c-index value.ConclusionsIntegrating瘤内UBR 5和CD 163 + TAM与当前的临床参数在预测ccRCC患者的术后预后中具有更好的准确性。
PurposeIdentification 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.MethodsThe 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.ResultsUBR5 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.ConclusionsIntegrating intratumoral UBR5 and CD163+TAMs with the current clinical parameters achieves better accuracy in predicting ccRCC patients’ postoperative prognosis.