Background: Growing findings have demonstrated that interferon regulatory transcription factor (IRF) family members are linked to the progression of various cancers. However, the roles of IRFs in clear cell renal cell carcinoma (ccRCC) remain undefined. Herein, we conducted a comprehensive analysis using the bioinformatics method to evaluate the expression patterns, clinical significance, and regulation of IRFs-related mechanisms in patients with ccRCC.
Methods: Data from the Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGA), and Gene Expression Omnibus (GEO) databases were used for investigation comprehensively. Specifically, we carried out a series of analyses to identify the candidate IRF and to explore its potential action mechanisms using the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. What is more, we emphatically investigate the association of candidate IRF with tumor immunity in ccRCC through the CIBERSORT algorithm, TIMER and GEPIA databases.
Results: Herein, IRF3 was identified as candidate IRF, which was highly expressed in ccRCC, and its overexpression was significantly associated with worse clinical outcomes and adverse overall survival. Uni- and multi-variate Cox regression analysis demonstrated that IRF3 overexpression was an independent predictor of worse prognosis. Functional enrichment analysis showed that IRF3 might participate in several cancer-related biological processes and signaling pathways, thereby promoting the progression of ccRCC. Additionally, we found that IRF3 was remarkably associated with tumor-infiltrating immune cells (TIICs) and various immune-related genes.
Conclusion: Herein, we identified IRF3 from the IRF gene family members, which could serve as promising prognostic marker and therapeutic target in ccRCC.



中文翻译：

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IRF3的过表达预测透明细胞肾细胞癌的预后不良

背景：越来越多的研究结果表明，干扰素调节转录因子 (IRF) 家族成员与各种癌症的进展有关。然而，IRF 在透明细胞肾细胞癌 (ccRCC) 中的作用仍未明确。在此，我们使用生物信息学方法进行了综合分析，以评估 ccRCC 患者 IRFs 相关机制的表达模式、临床意义和调控。
方法：来自癌症基因组图谱 (TCGA)、国际癌症基因组联盟 (ICGA) 和基因表达综合 (GEO) 数据库的数据被用于综合调查。具体来说，我们进行了一系列分析，以确定候选 IRF，并使用基因本体 (GO) 和京都基因和基因组百科全书 (KEGG) 通路分析探索其潜在的作用机制。更重要的是，我们通过CIBERSORT算法、TIMER和GEPIA数据库重点研究候选IRF与ccRCC肿瘤免疫的关系。
结果：在此，IRF3 被确定为候选 IRF，在 ccRCC 中高度表达，其过表达与较差的临床结果和不良的总体生存率显着相关。单变量和多变量 Cox 回归分析表明 IRF3 过表达是预后较差的独立预测因子。功能富集分析表明，IRF3可能参与多种癌症相关的生物学过程和信号通路，从而促进ccRCC的进展。此外，我们发现 IRF3 与肿瘤浸润免疫细胞 (TIIC) 和各种免疫相关基因显着相关。
结论：在此，我们从 IRF 基因家族成员中鉴定出 IRF3，可作为 ccRCC 的有前景的预后标志物和治疗靶点。