Overexpression of IRF3 Predicts Poor Prognosis in Clear Cell Renal Cell Carcinoma

Abstract

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.

The Role of Apoptotic Genes and Protein-Protein Interactions in Triple-negative Breast Cancer

“…According to previous studies, IRF3 induced apoptosis in BC cells (71), and IRF3 signaling is essential for triggering apoptosis in hormone-sensitive prostate cancer cells by activating intrinsic and extrinsic apoptotic pathways (72). On the other hand, clear cell renal cell carcinoma abundantly expressed IRF3, and its overexpression was strongly associated with worse clinical outcomes and overall adverse survival (73). Increasing proapoptotic protein expression in BC cells increases cytoplasmic NR4A1 and contributes to the process of apoptosis (74).…”

Statin prevents cancer development in chronic inflammation by blocking interleukin 33 expression

“…Accordingly, TBK1 inhibitors have tumor inhibitory effects associated with improved sensitivity to immunotherapy in several cancer types, including melanoma and liver cancer 59,60,62 . Moreover, activated TBK1-IRF3 signaling leads to the induction of angiogenesis factors, which is associated with poor prognosis in several cancers, including pancreatic cancer 57,[63][64][65] . Our ndings demonstrate that IL-33 is a target of TBK1-IRF3 signaling in cancer-prone tissues.…”

Identification of ZDHHC1 as a Pyroptosis Inducer and Potential Target in the Establishment of Pyroptosis-Related Signature in Localized Prostate Cancer

“…Recent findings hint at a potential mechanism of IRF1 targeting macrophage pyroptosis and inflammation in ACS and AS by promoting m6A modifications. Through comprehensive bioinformatics, Wu et al [46] confirm IRF3 as a putative prognostic biomarker and therapeutic target for ccRCC. IRF3 is a key YAP activator, implying that its pharmacological targeting with a small compound inhibitor can elicit broadened antitumor effects against YAP-driven human cancers [47].…”