Integration of intratumoral RASSF10 expression and tumor-associated macrophages into the established clinical indicators better predicts the prognosis of clear cell renal cell carcinoma patients
Integration of intratumoral RASSF10 expression and tumor-associated macrophages into the established clinical indicators better predicts the prognosis of clear cell renal cell carcinoma patients
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将瘤内RASSF10表达和肿瘤相关巨噬细胞整合到既定的临床指标中可以更好地预测透明细胞肾细胞癌患者的预后
DOI：
10.1080/2162402x.2020.1736793
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发表时间：
2020-01-01
期刊：
影响因子：
7.2
通讯作者：
Cui, Xingang
中科院分区：
文献类型：
--
作者：
Wang, Chao;Hong, Tianyu;Cui, Xingang
摘要肾透明细胞癌（ccRCC）患者术后预后的评估是至关重要的。本研究确定了将肿瘤内RASSF 10表达和肿瘤相关巨噬细胞（TAMs）与ccRCC患者中既定的临床病理指标相结合的预后价值。在来自在线数据库和ccRCC细胞系的ccRCC患者数据中分析RASSF 10表达。采用两个独立的ccRCC患者队列，通过免疫组织化学（IHC）和统计分析来检查RASSF 10和其他标志物的预后价值。我们发现RASSF 10表达在TCGA数据集和三个独立机构的ccRCC标本中下调。RASSF 10表达与ccRCC的疾病进展和TAM浸润呈负相关。此外，在两个独立的ccRCC患者队列中，低RASSF 10表达和高TAM浸润预测了高TNM分期、SSGN评分、WHO/ISUP分级和不良预后。此外，RASSF 10、CD 68或CD 163、TNM分期和SSGN评分被确定为预测ccRCC患者预后的独立危险因素。时间依赖性c指数分析显示，RASSF 10和TAM的组合在ccRCC患者的术后预后中产生比单独产生的指数更高的指数，并且RASSF 10和TAM与TNM分期或SSIGN评分的整合在评估ccRCC患者的预后中实现了最佳的准确性。这些结果在随机化培训、验证和合并队列中得到了验证。总之，RASSF 10-TAM分类器和当前临床参数的组合在预测ccRCC患者的术后结果方面产生了上级准确性。
ABSTRACT A helpful evaluation system is crucial for the postoperative prognosis prediction of clear cell renal cell carcinoma (ccRCC) patients. This study determined the prognostic value of combining intratumoral RASSF10 expression and tumor-associated macrophages (TAMs) with the established clinicopathological indicators in ccRCC patients. RASSF10 expression was analyzed in ccRCC patient data from online databases and ccRCC cell lines. Two independent ccRCC patient cohorts were employed to examine the prognostic value of RASSF10 and other markers by immunohistochemistry (IHC) and statistical analyses. We found that RASSF10 expression was downregulated in ccRCC specimens from the TCGA datasets and three independent institutions. RASSF10 expression was negatively correlated with disease progression and TAM infiltration in ccRCC. In addition, low RASSF10 expression and high TAM infiltration predicted a high TNM stage, SSIGN score, WHO/ISUP grading, and a poor prognosis in two independent ccRCC patient cohorts. Moreover, RASSF10, CD68 or CD163, TNM stage, and SSIGN score were identified as independent risk factors in predicting ccRCC patients’ prognosis. Time-dependent c-index analyses revealed that the combination of RASSF10 and TAMs resulted in a higher index than that resulting from each alone in the postoperative prognosis of ccRCC patients, and the integration of RASSF10 and TAMs with the TNM stage or SSIGN score achieved the best accuracy in assessing the prognosis of ccRCC patients. These findings were validated in the randomized training, validation, and combined cohorts. Taken together, the combination of the RASSF10-TAM classifier and current clinical parameters yields superior accuracy in predicting the ccRCC patients’ postoperative outcome.