Comprehensive analysis of the prognosis and biological significance for IFIT family in skin cutaneous melanoma

• Published in: International immunopharmacology 2021-12, Vol.101 (Pt A), p.108344-108344, Article 108344
• Main Authors: Jiang, Yuxiong, Zhang, Chen, Zhang, Jieping, Han, Dongxu, Shi, Xiujuan
• Format: Article
• Language: English
• Subjects: Adaptor Proteins, Signal Transducing - metabolism; Apoptosis; Apoptosis Regulatory Proteins - metabolism; Bioinformatics; Biomarkers; Biomarkers, Tumor - metabolism; Cancer; Cell cycle; Data analysis; Datasets; DNA Methylation; Gene Expression Regulation, Neoplastic; Humans; IFIT; Immune cell; Immune system; Interferon; Intracellular Signaling Peptides and Proteins - metabolism; Kaplan-Meier Estimate; Medical prognosis; Melanoma; Melanoma - diagnosis; Melanoma - metabolism; Melanoma - mortality; Mesenchyme; Microenvironments; MicroRNAs - metabolism; mRNA; N6-methyladenosine; Neoplasm Proteins - metabolism; Pax8 protein; Prognosis; Prognostic; Proportional Hazards Models; Regression analysis; Risk analysis; Risk factors; RNA, Long Noncoding - metabolism; RNA-Binding Proteins - metabolism; Sensitivity analysis; Skin; Skin - metabolism; skin cutaneous melanoma (SKCM); Skin Neoplasms - diagnosis; Skin Neoplasms - metabolism; Skin Neoplasms - mortality; Survival; Survival Analysis; TCGA; Transcriptome; Tumors
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2021.108344

•A first bioinformatics analysis of IFITs.•All four members of the IFIT family are dysregulated in SKCM.•The link between IFIT1/2/3/5 and 24 types of immune cells.•IFIT family can serve as diagnostic and prognostic markers of SKCM.•The key PAX8-AS1/Z83843.1-miR-92a-3p-IFIT2 axis is established. Interferon-induced protein with tetratricopeptide repeats (IFITs) genes, consisting of four members named IFIT1, IFIT2, IFIT3 and IFIT5, are involved in the progression of multiple cancer types, but their roles in skin cutaneous melanoma (SKCM) are still largely unknown. The TCGA-SKCM dataset, GSE15605 dataset and GSE100508 dataset were obtained in our study, and multiple online databases were used for data analysis and visualization, including GEPIA, GSCALite, MethSurv, DAVID, starBase and TIMER database. The mRNA expressing levels of all the four members included in IFIT family were elevated in SKCM tissues. In addition, ROC curve showed that the combined IFITs had a higher tumor prediction performance. Kaplan-Meier survival analysis revealed that the low expression of IFIT1/2/3/5 was associated with poor overall survival (OS) and disease-specific survival (DSS) in SKCM patients. Moreover, univariate and multivariate Cox regression analysis suggested that the low expression of IFIT2/3/5 was an independent risk factor for the prognosis of SKCM patients. Besides, cancer pathway activity analysis certified that the IFITs were involved in the apoptosis pathways, epithelial-mesenchymal transition (EMT) and cell cycle. Furthermore, drug sensitivity analysis indicated that the high expression of IFIT1/2/3 was sensitive to dasatinib drug. Additionally, the expressing levels of IFITs were found to be positively correlated with the level of immune cell infiltrates, immune biomarkers and m6A regulators. Finally, using bioinformatics analysis, we predicted that PAX8-AS1/Z83843.1-miR-92a-3p-IFIT2 axis might play crucial roles in the development and progression of SKCM. This study explored the prognostic values and biological significance of the IFITs in SKCM microenvironment. IFITs may serve as novel biomarkers for the diagnosis and prognosis of melanoma and potential immunotherapeutic targets.