Oral squamous cell carcinoma (OSCC) represents one of the most common head and neck cancer that with dire prognosis due partly to the lack of reliable prognostic biomarker. Here, we aimed to develop a CpG site-based prognostic signature through which we could accurately predict overall survival (OS) of patients with OSCC. We obtained OSCC-related DNA methylation and gene expression data sets from the public accessible Gene Expression Omnibus. Correlations between methylation level of CpG sites and OS of patients with OSCC were assessed by univariate Cox regression analysis followed by robust likelihood-based survival analysis on those CpG sites with permutation P < 0.05 for further screening the optimal CpG sites for OSCC OS prediction based on the risk score formula that composed of the methylation level of optimal CpG sites weighted by their regression coefficients. Besides, differential expression genes (DEGs) and differential methylation genes (DMGs) in OSCC samples compared with normal samples were obtained and shared genes were considered as vital genes in OSCC tumorgenesis and progression. As a result, two CpG sites including cg17892178 and cg17378966 that located in NID2 and IDO1, respectively, were identified as the optimal prognostic signatures for OSCC OS. In addition, 12 overlapping genes between DEGs and DMGs that closely associated with inflammation or blood and tissue development-related biological processes were obtained. In conclusions, this study should provide valuable signatures for OSCC diagnosis and treatment. K E Y W O R D SDNA methylation, gene expression, oral squamous cell carcinoma, overall survival, prognosis
BackgroundThe etiopathogenesis of chronic spontaneous urticaria (CSU) has not been fully understood, and there has been extensive interest in the interaction between inflammatory dermatosis and pyroptosis. This study intends to investigate the molecular mechanism of pyroptosis-related genes in CSU via bioinformatic ways, aiming at identifying the potential key biomarker.MethodsGSE72540, the RNA expression profile dataset of CSU, was utilized as the training set, and GSE57178 as the validation set. Differently expressed pyroptosis-related genes (DEPRGs), GO, KEGG, and DO analyses were performed. The hub genes were explored by the protein–protein interaction analysis. Moreover, CIBERSORT was employed for estimating immune cell types and proportions. Then, we constructed a DEmRNA–miRNA–DElncRNA ceRNA network and a drug–gene interaction network. Finally, ELISA was used for gene expression analysis.ResultsWe recognized 17 DEPRGs, whose enrichment analyses showed that they were mostly enriched in inflammatory response and immunomodulation. Moreover, 5 hub genes (IL1B, TNF, and IRF1 are upregulated, HMGB1 and P2RX7 are downregulated) were identified via the PPI network and verified by a validation set. Then immune infiltration analysis displayed that compared with normal tissue, CSU owned a significantly higher proportion of mast cells activated, but a lower proportion of T cells CD4 naive and so on. Furthermore, IL1B was statistically and positively associated with mast cells activated in CSU, and SNHG3, the upstream factor of IL1B in the ceRNA we constructed, also related with mast cells in CSU. Further analysis exhibited that the protein subcellular localization of IL1B was extracellular, according with its intercellular regulation role; IL1B was significantly correlated with key immune checkpoints; and the NOD-like receptor signaling pathway was the mainly involved pathway of IL1B based on the couple databases. What is more, the result of ELISA of CSU patients was the same as the above analyses about IL1B. In addition, the drug–gene interaction network contained 15 potential therapeutic drugs targeting IL1B, and molecular docking might make this relationship viable.ConclusionIL1B and its related molecules might play a key role in the development of CSU and could be potential biomarkers in CSU.
Purpose This study was meant to analyze immune infiltration and construct a ceRNA network to explore the new therapeutic targets for atopic dermatitis (AD) through bioinformatics way. Patients and Methods We downloaded the AD patients’ RNA expression profile datasets (GSE63741, GSE124700) from the Gene Expression Omnibus (GEO) database, which were analyzed through the GEO2R. We explored the hub genes by the enrichment analysis and the protein–protein interaction (PPI) analysis. Moreover, we estimated immune cell types and their proportions by ImmucellAI. GSE121212 dataset validation was performed to verify the robustness of the hub genes. Then, a ceRNA network was constructed by the miRWalk, miRNet, miRDB, DIANA, TargetScan, and starbase database. Finally, gene expression analysis was performed by using RT-qPCR. Results In total, we detected 22 differentially expressed genes (DEGs), which contained 8 downregulated genes and 14 upregulated genes. There were 5 hub genes confirmed as key genes through PPI network analysis and the ROC curves. KEGG pathway analysis revealed that they were significantly enriched in the IL-17 signaling pathway and GO analysis showed mainly in the immune cell chemotaxis. The immune infiltration profiles were different between normal controls and AD, and each of the key genes (S100A7, S100A8, S100A9, and LCE3D) was significantly correlated with the main infiltration cell of AD. A lncRNA–miRNA–mRNA ceRNA network containing the key genes was constructed, and NEAT1 and XIST, the core of ceRNA network, were significantly overexpressing verified by RT-qPCR in AD patients. Conclusion Altogether, the key genes and their ceRNA network provided a novel perspective to the immunomodulation of AD, which may be potential and new therapeutic targets for AD.
Oral squamous cell carcinoma (OSCC) is an aggressive and common malignancy in the head and neck, characterized by poor prognosis and high incidence. This study aimed to investigate the role of long noncoding RNA TFAP2A-AS1 in OSCC. The competing endogenous RNA network of TFAP2A-AS1 was constructed by bioinformatics analysis. The expressions of miR-1297, TFAP2A-AS1, and TFAP2Awere measured by quantitative reverse transcription-polymerase chain reaction.The correlations of TFAP2A-AS1, miR-1297, and TFAP2A with clinicopathological characteristics of OSCC were assessed. RNA immunoprecipitation and dual-luciferase reporter assay were used to identify the target of miR-1297. Cell proliferation was measured by colony formation assay and [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium] assay. Transwell assay and wound healing assay were performed to assess cell movement. TFAP2A-AS1 and TFAP2A were upregulated in OSCC and their expression levels were positively correlated. The levels of TFAP2A-AS1, miR-1297, and TFAP2A were also associated with lymphatic metastasis and the tumor-node-metastasis (TNM) stage of OSCC patients. TFAP2A-AS1 acted as a miR-1297 sponge. OSCC cell growth and movement were inhibited by miR-1297.Changes in the miR-1297 expression abolished the effects of TFAP2A-AS1 on OSCC cells. Additionally, TFAP2A was a target of miR-1297. TFAP2A promoted OSCC cell growth and migration/invasion, indicating that TFAP2A mediated the effects of TFAP2A-AS1 and miR-1297. TFAP2A-AS1 exerts an oncogenic effect in OSCC via the TFAP2A-AS1/miR-1297/TFAP2A axis, which may provide new targets and strategies for OSCC treatments
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