Xu Wen-Hao, Xu Yue, Wang Jun, Wan Fang-Ning, Wang Hong-Kai, Cao Da-Long, Shi Guo-Hai, Qu Yuan-Yuan, Zhang Hai-Liang, Ye Ding-Wei
Department of Urology, Fudan University Shanghai Cancer Center, Shanghai 200032, P.R. China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, P.R. China.
Aging (Albany NY). 2019 Sep 7;11(17):6999-7020. doi: 10.18632/aging.102233.
Growing evidence has highlighted the immune response as an important feature of carcinogenesis and therapeutic efficacy in clear cell renal cell carcinoma (ccRCC). This study categorized ccRCC cases into high and low score groups based on their immune/stromal scores generated by the ESTIMATE algorithm, and identified an association between these scores and prognosis. Differentially expressed tumor environment (TME)-related genes extracted from common upregulated components in immune and stromal scores were described using functional annotations and protein-protein interaction (PPI) networks. Most PPIs were selected for further prognostic investigation. Many additional previously neglected signatures, including , exhibited significant prognostic potential. In addition, multivariate Cox analysis indicated that and were the most significant prognostic signatures, and were closely related to immune infiltration in TCGA cohort. External prognostic validation of and was undertaken in 380 ccRCC cases from a real-world cohort. These findings indicate the relevance of monitoring and manipulation of the microenvironment for ccRCC prognosis and precision immunotherapy.
越来越多的证据表明，免疫反应是透明细胞肾细胞癌（ccRCC）致癌作用和治疗效果的一个重要特征。本研究根据ESTIMATE算法生成的免疫/基质评分将ccRCC病例分为高分和低分两组，并确定了这些评分与预后之间的关联。从免疫和基质评分中共同上调的成分中提取的差异表达肿瘤微环境（TME）相关基因，使用功能注释和蛋白质-蛋白质相互作用（PPI）网络进行描述。大多数PPI被选用于进一步的预后研究。许多其他先前被忽视的特征，包括 ，表现出显著的预后潜力。此外，多变量Cox分析表明， 和 是最显著的预后特征，并且与TCGA队列中的免疫浸润密切相关。在来自真实世界队列的380例ccRCC病例中对 和 进行了外部预后验证。这些发现表明监测和调控微环境对于ccRCC预后和精准免疫治疗的重要性。
