PDF(Pubmed)
Abstract：
Immune-related enhancer RNAs (eRNAs) have garnered significant attention in cancer metabolism research, yet their specific roles in ccRCC have remained elusive.
We retrieved eRNA expression profiles from TCGA database and identified immune-related eRNAs (IREs) by assessing their co-expression with immune genes. Utilizing consensus clustering, we organized these IREs into two distinct clusters. The construction of an IREs signature was accomplished through the LASSO and multivariate Cox analysis. Furthermore, we performed Cell Counting Kit-8 and clonogenic assays to assess changes in the proliferative capacity of Caki-1 and 769-P cells.
The existence of two clusters of immune-related eRNAs in ccRCC, each with distinctive prognostic and immunological attributes. Cluster B exhibited immunosuppressive properties and displayed a positive correlation with immunosuppressive cells. Functional enrichment analysis unveiled their involvement in several tumor-promoting pathways, metabolic pathways and immune pathways. The IREs signature demonstrated its potential to accurately predict patient immune and prognostic characteristics. AC003092.1, an eRNA strongly associated with patient survival, emerged as a potential oncogene significantly linked to adverse prognosis and the presence of immunosuppressive cells and checkpoints in ccRCC patients. Notably, AC003092.1 displayed marked upregulation in ccRCC tissues and cell lines, and its knockdown substantially inhibited the proliferation of Caki-1 and 769-P cells.
We established a robust predictive model that played a vital role in determining the prognosis, clinicopathological characteristics and immune cell infiltration patterns of ccRCC patients. IRE, particularly AC003092.1, which was strongly associated with survival, hold promise as novel immunotherapeutic targets for ccRCC.
We retrieved eRNA expression profiles from TCGA database and identified immune-related eRNAs (IREs) by assessing their co-expression with immune genes. Utilizing consensus clustering, we organized these IREs into two distinct clusters. The construction of an IREs signature was accomplished through the LASSO and multivariate Cox analysis. Furthermore, we performed Cell Counting Kit-8 and clonogenic assays to assess changes in the proliferative capacity of Caki-1 and 769-P cells.
The existence of two clusters of immune-related eRNAs in ccRCC, each with distinctive prognostic and immunological attributes. Cluster B exhibited immunosuppressive properties and displayed a positive correlation with immunosuppressive cells. Functional enrichment analysis unveiled their involvement in several tumor-promoting pathways, metabolic pathways and immune pathways. The IREs signature demonstrated its potential to accurately predict patient immune and prognostic characteristics. AC003092.1, an eRNA strongly associated with patient survival, emerged as a potential oncogene significantly linked to adverse prognosis and the presence of immunosuppressive cells and checkpoints in ccRCC patients. Notably, AC003092.1 displayed marked upregulation in ccRCC tissues and cell lines, and its knockdown substantially inhibited the proliferation of Caki-1 and 769-P cells.
We established a robust predictive model that played a vital role in determining the prognosis, clinicopathological characteristics and immune cell infiltration patterns of ccRCC patients. IRE, particularly AC003092.1, which was strongly associated with survival, hold promise as novel immunotherapeutic targets for ccRCC.
摘要：
背景：免疫相关增强子RNA（eRNA）在癌症代谢研究中引起了广泛关注，然而，它们在ccRCC中的具体作用仍然难以捉摸。
方法：我们从TCGA数据库检索了eRNA表达谱，并通过评估其与免疫基因的共表达来鉴定免疫相关eRNA（IRE）。利用共识聚类，我们将这些IRE组织成两个不同的集群。通过LASSO和多变量Cox分析完成IRE特征的构建。此外，我们进行了细胞计数试剂盒-8和克隆形成试验,以评估Caki-1和769-P细胞增殖能力的变化.
结果：在ccRCC中存在两个免疫相关eRNAs簇，每个都具有独特的预后和免疫学属性。簇B表现出免疫抑制特性，并与免疫抑制细胞呈正相关。功能富集分析揭示了它们参与几种肿瘤促进途径，代谢途径和免疫途径。IRE签名证明了其准确预测患者免疫和预后特征的潜力。AC003092.1，一种与患者生存密切相关的eRNA，作为潜在的癌基因出现与ccRCC患者的不良预后以及免疫抑制细胞和检查点的存在显着相关。值得注意的是,AC003092.1在ccRCC组织和细胞系中显示出明显的上调，其敲除显著抑制Caki-1和769-P细胞的增殖。
结论：我们建立了一个稳健的预测模型，该模型在确定预后中起着至关重要的作用，ccRCC患者的临床病理特征和免疫细胞浸润模式。IRE,特别是AC003092.1，与生存率密切相关，有望成为ccRCC的新型免疫治疗靶点。
方法：我们从TCGA数据库检索了eRNA表达谱，并通过评估其与免疫基因的共表达来鉴定免疫相关eRNA（IRE）。利用共识聚类，我们将这些IRE组织成两个不同的集群。通过LASSO和多变量Cox分析完成IRE特征的构建。此外，我们进行了细胞计数试剂盒-8和克隆形成试验,以评估Caki-1和769-P细胞增殖能力的变化.
结果：在ccRCC中存在两个免疫相关eRNAs簇，每个都具有独特的预后和免疫学属性。簇B表现出免疫抑制特性，并与免疫抑制细胞呈正相关。功能富集分析揭示了它们参与几种肿瘤促进途径，代谢途径和免疫途径。IRE签名证明了其准确预测患者免疫和预后特征的潜力。AC003092.1，一种与患者生存密切相关的eRNA，作为潜在的癌基因出现与ccRCC患者的不良预后以及免疫抑制细胞和检查点的存在显着相关。值得注意的是,AC003092.1在ccRCC组织和细胞系中显示出明显的上调，其敲除显著抑制Caki-1和769-P细胞的增殖。
结论：我们建立了一个稳健的预测模型，该模型在确定预后中起着至关重要的作用，ccRCC患者的临床病理特征和免疫细胞浸润模式。IRE,特别是AC003092.1，与生存率密切相关，有望成为ccRCC的新型免疫治疗靶点。
