Integrated Transcriptomic and Immune Landscape Profiling Identifies CXCR2 and IL1RN as Key Immune-Related Downregulated Genes in Oral Squamous Cell Carcinoma.
Abstract
Background
Oral squamous cell carcinoma (OSCC) is among the most common head and neck cancers, representing about 90% of all cases. Despite advances in treatment, the prognosis remains poor, mainly owing to the complex immunosuppressive tumor microenvironment.
Methods
The GEO2R tool was used to screen differentially expressed genes (DEGs) in two GEO microarray datasets (GSE74530 and GSE37991). Genes meeting the criteria of adjusted P < 0.05 and |log2FC| ≥ 1 were considered significantly differentially expressed. Venn diagrams were constructed to illustrate the DEGs shared by the two datasets. Protein-protein interaction (PPI) networks were constructed by STRING and visualized in Cytoscape, and hub genes were identified according to centrality metrics. GEPIA was used to further validate hub gene expression. DAVID was used to perform functional enrichment analyses (GO and KEGG) with a significance threshold of P<0.05. The m6A-related regulation was analyzed by RM2Target, the interaction of transcription factors was predicted by TRRUST, and immune infiltration was analyzed by TIMER 2.0.
Results
We found 186 overlapping DEGs. PPI network analysis identified 40 hub genes, with CXCR2 and IL1RN prioritized due to their high network centrality and immune relevance. Both CXCR2 and IL1RN were significantly downregulated in tumor tissues compared with normal tissues. Validation by GEPIA and TCGA-HNSC data confirmed significant downregulation of both genes in tumor tissues. Immune infiltration analysis revealed that the up-regulation of CXCR2 and IL1RN was negatively correlated with the infiltration of key anti-tumor immune cells. NF-κB and STAT3 were identified as major regulators of these genes by transcription factor analysis.
Conclusion
Our comprehensive bioinformatics analysis identified CXCR2 and IL1RN as the immune-related hub genes that were consistently down-regulated in OSCC. These findings imply their potential involvement in tumor immune escape and identify them as promising candidates for prognostic biomarkers and immunotherapy targets. This deserves experimental validation.