Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China.
Center for Evidence-Based and Translational Medicine, Zhongnan Hospital of Wuhan University, Wuhan, China.
J Cell Mol Med. 2021 Apr;25(7):3258-3271. doi: 10.1111/jcmm.16395. Epub 2021 Feb 19.
The immunophenotype of bladder cancer plays a pivotal role in the prognosis of cancer, but the effect of different epigenetic factors on different immunophenotypes in bladder tumours remains unclear. This study used multi-omics data analysis to provide molecular basis support for different immune phenotypes. Unsupervised cluster analysis revealed distinct subclusters with higher (subcluster B2) or lower cytotoxic immune phenotypes (subcluster A1) related to PD-L1 and IFNG expression. Mutational landscape analyses showed that the mutation level of TP53 in subcluster B1 was highest than other subclusters, and subcluster B1 had a lower frequency of concurrent mutation than subcluster A2. A total of 2364 differentially expressed genes were identified between subclusters A2 and B1, and the main functions of the up-regulated genes in subcluster B1 were enriched in the activation of T cells and other related pathways. We found that STAT1 was a key gene in a gene regulatory network related to immune phenotypes in bladder cancer. Finally, we constructed a prognostic prediction model by LASSO Cox regression which could distinguish high-risk and low-risk cases significantly. In conclusion, the present study addressed a field synopsis between genetic and epigenetic events in immune phenotypes of bladder cancer.
膀胱癌的免疫表型在癌症预后中起着关键作用,但不同表观遗传因素对膀胱癌不同免疫表型的影响尚不清楚。本研究使用多组学数据分析为不同免疫表型提供分子基础支持。无监督聚类分析揭示了具有更高细胞毒性免疫表型(亚群 B2)或更低细胞毒性免疫表型(亚群 A1)的不同亚群,与 PD-L1 和 IFNG 表达相关。突变景观分析表明,亚群 B1 中 TP53 的突变水平高于其他亚群,且亚群 B1 中同时发生突变的频率低于亚群 A2。在亚群 A2 和 B1 之间鉴定出 2364 个差异表达基因,亚群 B1 中上调基因的主要功能富集在 T 细胞激活和其他相关途径中。我们发现 STAT1 是膀胱癌免疫表型相关基因调控网络中的关键基因。最后,我们通过 LASSO Cox 回归构建了一个预后预测模型,能够显著区分高风险和低风险病例。总之,本研究解决了膀胱癌免疫表型中遗传和表观遗传事件之间的领域综述。