CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题：EZH2-regulated immune risk score prognostic model predicts outcome of clear cell renal cell carcinoma.
EZH2-regulated immune risk score prognostic model predicts outcome of clear cell renal cell carcinoma.
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EZH2 调控的免疫风险评分预后模型是一个独立的预后因素，具有良好的准确性和可预测性，可为临床领域提供实验数据。
zeste同源物2增强子（EZH2）在肿瘤微环境（TME）中发挥重要作用，并且EZH2在塑造CD8+ T细胞命运和功能的表观遗传景观中起作用，尤其侧重于癌症。在这里，EZH2高表达总是导致CD8+ T细胞浸润减少。然而，据报道，透明细胞肾细胞癌（ccRCC）是一种“热”肿瘤，却矛盾地具有高EZH2表达。我们的目标是构建一个EZH2调控的免疫风险评分预后模型来预测ccRCC结局，并为临床EZH2抑制剂在免疫治疗中微调T细胞反应提供前景。
我们下载并分析了癌症基因组图谱（TCGA）、癌细胞系百科全书（CCLE）、TISIDB数据库和WebGestalt，用于ccRCC患者、EZH2相关TIL（肿瘤浸润淋巴细胞）和免疫调节因子。下载了R包“limma”、“BiocManager”和“preprocessCore”等，以准备CIBERSORT文件、免疫细胞热图、多变量Cox模型和生存分析。EZH2调控的免疫风险模型的预后能力通过在R studio中的受试者工作特征（ROC）和曲线下面积（AUC）分析进行计算。
EZH2在ccRCC中高表达并与不良预后相关。然而，EZH2高表达与“冷”肿瘤无关。在EZH2显著调控的49个免疫调节因子中，森林图显示26个免疫调节因子特征与总生存期独立相关。EZH2调控的免疫风险评分预后模型是一个独立预后因素（AUC=0.816），尤其是在与ccRCC临床病理参数联合用于总生存期预测时。
The enhancer of zeste homolog 2 (EZH2) plays an important role in the tumor microenvironment (TME), and EZH2 in shaping the epigenetic landscape of CD8 + T cell fate and function, with a particular emphasis on cancer. Here, high EZH2 expression always leads to less CD8 + T cell infiltration. However, clear cell renal cell carcinoma (ccRCC) is reportedly a "hot" tumor, with contradictory high EZH2 expression. Our goal was to construct a EZH2-regulated immune risk score prognostic model to predict ccRCC outcomes, and provide a prospect of clinical EZH2 inhibitors in fine-tuning T cell responses with immune therapy.
We downloaded and analyzed The Cancer Genome Atlas (TCGA), Cancer Cell Line Encyclopedia (CCLE), TISIDB database, and WebGestalt for ccRCC patients, EZH2-related tumor-infiltrating lymphocytes and immunomodulators. R packages "limma", "BiocManager", and "preprocessCore", etc. were downloaded to prepare CIBERSORT files, immune cells heatmap, multivariable Cox model and survival analysis. The EZH2-regulated immune risk model's prognostic ability was calculated by receiver operating characteristic (ROC) and area under the curve (AUC) analyses in R studio.
EZH2 was highly expressed and related to poor outcome in ccRCC. However, high-expression EZH2 was not related to a "cool" tumor. Of the 49 immunomodulators significantly regulated by EZH2, forest plot showed 26 immunomodulators signatures independently associated with overall survival. The EZH2-regulated immune-risk score prognostic model was an independent prognostic factor (AUC =0.816), especially combined with clinicopathologic parameters in ccRCC overall survival prediction.
The EZH2-regulated immune-risk score prognostic model was an independent prognostic factor, with good accuracy and predictability, and could provide experimental data to the clinical area.
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