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The type I interferon (IFN-I) response is a critical component of the immune defense against various viral pathogens, triggering the expression of hundreds of interferon-stimulated genes (ISGs). These ISGs encode proteins with diverse antiviral functions, targeting various stages of viral replication and restricting infection spread. Beyond their antiviral functions, ISGs and associated immune metabolites have emerged as promising broad-spectrum biomarkers that can differentiate viral infections from other conditions. This review provides an overview of the diagnostic potential of ISGs at transcript and protein levels, as well as their immune metabolites. We focus on their clinical applications and the sensitivity and specificity of these biomarkers through receiver operating characteristic (ROC) analysis. We highlight the need for further research to facilitate the effective translation of these biomarkers into clinical practice. [ABSTRACT FROM AUTHOR]

Abstract This study aimed to investigate the expression levels and clinical implications of interferon α inducible protein 27 (IFI27) and the N6-methyladenosine (m6A) regulator Alkylation repair homolog 5 (ALKBH5) in head and neck squamous cell carcinoma (HNSCC). We employed bioinformatics methods to analyze the differential expression of IFI27 in HNSCC and its prognostic implications. Additionally, we explored the pathways and mechanisms associated with its enrichment. Immunohistochemistry (IHC) was used to detect the expression of IFI27 protein in HNSCC and adjacent normal tissues. IFI27 expression was significantly up-regulated in HNSCC (P

ABSTRACT Background Chemo‐resistance is a major obstacle to the treatment of esophageal squamous cell carcinoma (ESCC). Interferon alpha‐inducible protein 27 (IFI27) has been reported to be associated with ESCC progression. This study is designed to explore the role and mechanism of IFI27 in the cisplatin (DDP) resistance of ESCC. Methods IFI27 and Ubiquitin‐specific peptidase 18 (USP18) levels were detected by real‐time quantitative polymerase chain reaction (RT‐qPCR). IFI27, multidrug resistance‐associated protein 1 (MRP1), USP18, and Homeobox A5 (HOXA5) protein levels were determined using western blot. DDP resistance, cell viability, proliferation, apoptosis, invasion, and migration were assessed using MTT, EdU, flow cytometry, transwell, and wound healing. Interaction between USP18 and IFI27 was verified using Co‐immunoprecipitation (CoIP) assay. Binding between HOXA5 and USP18 promoter was predicted by JASPAR and validated using Chromatin immunoprecipitation (ChIP) and dual‐luciferase reporter assays. Results IFI27 was upregulated in DDP‐resistant ESCC tissues and cells. IFI27 knockdown repressed DDP resistance, cell proliferation, invasion, migration, and induced cell apoptosis in vitro. Mechanistically, USP18 induced the deubiquitination of IFI27 and prevented its degradation. Furthermore, HOXA5 was a transcription factor of USP18 and activated the transcriptional activity of USP18 via binding to its promoter region. Conclusion USP18 transcriptionally mediated by HOXA5 could promote cell malignant behaviors and DDP resistance through deubiquitinating IFI27, providing a promising therapeutic target for ESCC treatment.

IFI27, an interferon (IFN)-stimulated gene, is emerging as a crucial player in immune responses across various species, with significant implications for precision medicine. Commonly found among the most upregulated genes in infections, cancers, as well as inflammatory and autoimmune disorders, IFI27 is ready to be trialed in clinical practice for certain indications, and holds promise as an immunomodulatory target. We hypothesize that IFI27 plays a dual role, typically supporting immune defense but sometimes contributing to disease progression, which might render it a putative biomarker for diagnosis, prognosis, and treatment response. We advocate for focused research on IFI27 to unlock its potential in precision medicine and to contribute to a unifying framework of its mechanisms in the immune response. Our viewpoint is supported by numerous studies highlighting IFI27's involvement across various conditions and the possibilities for clinical application., Competing Interests: Declaration of interests The authors have no conflicts of interest to disclose., (Copyright © 2025 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Dysregulation of m6A modification has emerged as a vital factor in the development of esophageal squamous cell carcinoma (ESCC). Here, we sought to explore the critical role of m6A methylation mediated by the m6A methyltransferase METTL3 in ESCC. Protein expression analysis was performed by immunohistochemistry and immunoblot assays. The mRNA levels of METTL3 and IFI27 were detected by quantitative PCR. Cell sphere formation potential, migration, invasiveness, apoptosis, proliferation and viability were assessed by standard sphere formation, wound healing, transwell, flow cytometry, EdU and CCK-8 assays, respectively. The impact of METTL3 or IGF2BP2 on IFI27 mRNA was evaluated by methylated RNA immunoprecipitation (MeRIP), RIP or mRNA stability analysis. Xenograft assays were used to detect the in vivo function of METTL3. Elevated levels of METTL3 were observed in ESCC tumors and cells, and these increased levels were associated with the declined prognosis of ESCC. MELLT3 depletion impeded ESCC cell growth, invasiveness, migration, and sphere formation, and induced cell apoptosis in vitro. Elevated IFI27 expression was positively correlated with METTL3 levels in ESCC. Moreover, METTL3 mediated m6A methylation of IFI27 mRNA to stabilize the mRNA. The m6A reader IGF2BP2 also affected m6A methylation and expression of IFI27 mRNA. Additionally, IFI27 re-expression had a counteracting impact on the effects of METTL3 deficiency on in vitro ESCC cell behaviors and in vivo KYSE30 xenograft growth. Our findings demonstrate that METTL3-mediated IFI27 mRNA m6A methylation drives ESCC development through an IGF2BP2-dependent mechanism. Blocking the METTL3/IFI27 axis may be effective for preventing ESCC., (© 2025 Wiley Periodicals LLC.)

Neuroblastoma (NB) is a prevalent extracranial malignant neuroendocrine tumor in children, originating from the sympathetic nervous system. This study aims to investigate new therapeutic targets for NB. The differentially expressed genes were screened by analyzing the GSE35133 and GSE90689 datasets. Hub genes were identified by constructing a protein-protein interaction network. The diagnostic value of the hub genes was assessed through the analysis of receiver operating characteristic (ROC) curves and the expression, prognosis, and immune infiltration of IFI27 in pan-cancer were analyzed on the online website Sangerbox. The hub gene expression levels were validated by performing real-time reverse transcriptase-polymerase chain reaction. The functions of IFI27 in NB were investigated by Cell Counting Kit-8, 5-ethynyl-2'-deoxyuridine, wound healing, and Transwell assays. Six candidate genes (IFI27, TNFSF10, IFI44, DDX58, HIST1H1C, and HIST1H1E) were identified as potential diagnostic biomarkers for NB. The expression levels of IFI27, TNFSF10, IFI44, and DDX58 were significantly decreased, while HIST1H1C and HIST1H1E were elevated. Notably, IFI27 displayed correlations with prognosis and immune infiltration in multiple tumors. In vitro, functional assays demonstrated that the knockdown of IFI27 promoted the proliferation, migration, and invasion of U251 cells. Conversely, in SK-N-AS cells, IFI27 overexpression inhibited cell proliferation, migration, and invasion. IFI27 was lowly expressed in NB and participated in the progression of NB, which provides a new insight into the pathogenic mechanism and novel therapeutic strategy for NB., Competing Interests: Declarations. Competing Interests: The authors declare no competing interests. Ethical approval: Not applicable. Consent for publication: Not applicable. Consent to participate: Not applicable., (© 2025. The Author(s), under exclusive licence to Springer Nature B.V.)