Exploring Prognostic Immune Microenvironment-Related Genes in Head and Neck Squamous Cell Carcinoma from the TCGA Database.

Abstract

Purpose: Head and neck squamous cell carcinoma (HNSCC) has a high rate of local and distant metastases. In tumor tissues, the interaction between tumor cells and the tumor microenvironment (TME) is closely related to cancer development and prognosis. Therefore, screening for TME-related genes in HNSCC is crucial for understanding metastatic patterns. Methods: Our research relied mainly on a novel algorithm called Estimation of STromal and Immune cells in MAlignant Tumors using Expression data (ESTIMATE). Fragments Per Kilobase of exon model per Million mapped fragments (FPKM) data and HNSCC clinical data were obtained from the TCGA database, and the purity of HNSCC tissue and the features of stromal and immune cell infiltration were determined. Furthermore, differentially expressed genes (DEGs) were screened based on immune, stromal, and ESTIMATE scores, and their protein-protein interaction (PPI) networks and ClueGO functions were evaluated. Finally, the expression profiles of DEGs related to immunity in HNSCC were determined. Differential gene expression was verified in the highly invasive oral cancer cell lines (SCC-25, CAL-27, and FaDu) and oral cancer tissues. Results: Our analysis found that both the immune and ESTIMATE scores were significantly associated with the prognosis of HNSCC. Moreover, cross-validation using the Venn algorithm revealed that 433 genes were significantly upregulated, and 394 genes were significantly downregulated. All DEGs were associated with both ESTIMATE and immune scores. The enrichment of cytokine-cytokine receptor interactions and chemokine signaling pathways was observed using pathway enrichment analyses. We initially screened 25 genes after analyzing the key sub-networks of the PPI network. Survival analysis revealed the significance of CCR4, CXCR3, P2RY14, CCR2, CCR8, and CCL19 in relation to survival and their association with immune infiltration-related metastasis in HNSCC. Conclusions: The expression profiles of relevant TME-related genes were screened following stromal and immune cell scoring using ESTIMATE, and DEGs associated with survival were identified. These TME-related gene markers offer valuable utility as both prognostic indicators and markers denoting metastatic traits in HNSCC.