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Comprehensive insights on pivotal prognostic signature involved in clear cell renal cell carcinoma microenvironment using the ESTIMATE algorithm

机译:使用ESTIMATE算法全面了解透明细胞肾细胞癌微环境所涉及的关键预后标志

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摘要

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 , 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.
机译:越来越多的证据表明,免疫细胞和基质细胞构成了肿瘤微环境(TME)的大部分,在肿瘤的进展中起着重要的作用。在我们的研究中,我们旨在筛选与TME相关的在透明细胞肾细胞癌(ccRCC)中重要的预后标志。我们从TCGA数据库中获得了总共611个样本,其中包括转录组概况和临床数据。采用ESTIMATE算法估计免疫/基质细胞的浸润率。我们发现,免疫评分比基质评分在总体生存率和与危险临床因素的正相关性方面显示出更多的预后意义。我们在Immunescore和stromalscore组之间进行了差异表达分析,以获得72个交叉基因。进行蛋白质间相互作用(PPI)网络和功能分析,以表明可能改变的途径。此外,我们进一步进行了多变量Cox分析,使用逐步回归程序鉴定了与ccRCC的TME高度相关的12个中心基因。因此,从多元Cox结果构建风险评分,并使用接收者操作特征(ROC)曲线评估预测值(AUC = 0.781)。高风险评分的ccRCC患者的生存结局比低风险评分的患者差。在来自的验证队列中,TNFSF13B,CASP5和GJB6与肿瘤阶段呈正相关,而FREM1与肿瘤阶段呈负相关。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显示出显着相关性。综上所述,我们的研究使用转录组图谱鉴定了与ccRCC TME中基质细胞和免疫细胞浸润有关的特定特征,从而对ccRCC中的肿瘤微环境有了全面的了解。

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