Department of Urology, Shanghai Fourth People's Hospital affiliated to Tongji University School of Medicine, Shanghai, China.
The First Clinical Medical College of Nanjing Medical University, Nanjing, China.
Cancer Med. 2020 Jun;9(12):4310-4323. doi: 10.1002/cam4.2983. Epub 2020 Apr 20.
Emerging evidence has highlighted that the immune and stromal cells formed the majority of tumor microenvironment (TME) which are served as important roles in tumor progression. In our study, we aimed to screen vital prognostic signature associated with TME in clear cell renal cell carcinoma (ccRCC). We obtained total 611 samples from TCGA database consisting of transcriptome profiles and clinical data. ESTIMATE algorithm was applied to estimate the infiltrating fractions of immune/stromal cells. We found that the immune scores revealed more prognostic significance in overall survival and positive associations with risk clinical factors than stromal scores. We carried out differential expression analysis between Immunescore and stromalscore groups to obtain the 72 intersect genes. Protein to protein interaction (PPI) network and functional analysis was performed to indicate potential altered pathways. Additionally, we further conducted multivariate Cox analysis to identify 12 hub genes associated highly with TME of ccRCC using a stepwise regression procedure. Accordingly, risk score was constructed from the multivariate Cox results and Receiver Operating Characteristic (ROC) curve was used to assess the predictive value (AUC = 0.781). The ccRCC patients with high risk scores suffered poor survival outcomes than that with low risk scores. In the validation cohort from GSE53757, TNFSF13B, CASP5, and GJB6 correlated positively with tumor stages, while FREM1 negatively correlated with tumor stages. Importantly, we further observed that TNFSF13B, CASP5 and XCR1 showed the remarkable correlations with tumor-infiltrating immune cells. Taken together, our research identified specific signatures that related to the infiltration of stromal and immune cells in TME of ccRCC using the transciptome profiles, which reached a comprehensive understanding of tumor microenvironment in ccRCC.
新出现的证据强调了免疫细胞和基质细胞构成了肿瘤微环境（TME）的大部分，它们在肿瘤进展中起着重要作用。在我们的研究中，我们旨在筛选与透明细胞肾细胞癌（ccRCC）TME 相关的重要预后特征。我们从 TCGA 数据库中获得了总共 611 个样本，其中包括转录组谱和临床数据。ESTIMATE 算法被用来估计免疫/基质细胞的浸润分数。我们发现，免疫评分在总生存率方面显示出更具预后意义，并且与风险临床因素呈正相关，而基质评分则不然。我们对 Immunescore 和 stromalscore 组之间进行了差异表达分析，以获得 72 个交集基因。进行蛋白质相互作用（PPI）网络和功能分析以指示潜在改变的途径。此外，我们使用逐步回归程序，通过多变量 Cox 分析进一步确定与 ccRCC TME 高度相关的 12 个枢纽基因。相应地，从多变量 Cox 结果构建风险评分，并使用接收器操作特征（ROC）曲线评估预测价值（AUC=0.781）。风险评分较高的 ccRCC 患者的生存结果比风险评分较低的患者差。在来自 GSE53757 的验证队列中，TNFSF13B、CASP5 和 GJB6 与肿瘤分期呈正相关，而 FREM1 与肿瘤分期呈负相关。重要的是，我们进一步观察到 TNFSF13B、CASP5 和 XCR1 与肿瘤浸润免疫细胞呈显著相关。总之，我们使用转录组谱研究确定了与 ccRCC TME 中基质和免疫细胞浸润相关的特定特征，从而全面了解了 ccRCC 中的肿瘤微环境。
