Identification and Validation of m7G-Related Prognostic Signatures and Associated Regulatory Axis in Head and Neck Squamous Cell Carcinoma

Abstract

Abstract Background: N7-methylguanosine (m7G) methylation is a widespread modification in RNA, which is very important for various biological functions and is closely associated with the occurrence and development of cancer. However, the expression of m7G methylation-related genes (m7GRGs) in head and neck squamous cell carcinoma (HNSCC) and its correlation with prognosis remain unclear. Methods: In this study, the expression pattern and prognosis of m7GRGs in TCGA-HNSCC was discussed through a public database. The differentially expressed genes (DEGs) between high and low expression groups of m7GRGs were identified, and their functional enrichment was analyzed. The prognostic m7GRG expression in HNSCC was verified by real-time quantitative PCR(RT-qPCR). LASSO-Cox regression analysis was performed to construct a prognostic model and predictive nomogram. In addition, the relationship between the expression of prognostic m7GRGs in HNSCC and clinicopathological features, copy number variation (CNV), tumor microenvironment (TME), tumor mutation burden (TMB), microsatellite instability (MSI), ESTIMATE, mRNA stemness index (mRNAsi), and drug sensitivity was evaluated. Finally, the competitive endogenous RNA (ceRNA) regulatory network was constructed based on the expression level of prognostic m7GRGs. Results: m7GRGs were closely related to cell cycle, DNA replication and repair, and focal adhesion, among other factors. The gene mutation map of m7GRGs in HNSCC was summarized. Further, an HNSCC-related prognostic model including four prognostic biomarkers (EIF3D, EIF1, LARP1, and METTL1) was constructed. The verification of RT-qPCR data further confirmed the upregulated expression of prognostic m7GRGs in HNSCC. Prognostic m7GRGs were significantly correlated with tumor stage, grade, TMB, MSI, immune infiltration, mRNAsi, and drug sensitivity. Finally, the LINC00707/hsa-miR-30b-5p/LARP1 and SNHG16/hsa-miR-30b-5p/LARP1 regulatory axes of HNSCC were constructed. Conclusion: We found a significant correlation between the abnormal expression of m7GRGs and the prognosis of patients with HNSCC. We identified four m7GRGs prognostic models that can effectively evaluate the prognosis of patients with HNSCC, and these provide a basis for individualized treatment and immunotherapy decision-making in HNSCC patients.