A novel m7G regulator‐based methylation patterns in head and neck squamous cell carcinoma

Abstract

AbstractAbnormal RNA N7‐methylguanosine (m7G) modification is known to contribute to effects on tumor occurrence and development. Nevertheless, the mechanisms of its function in immunoregulation, tumor microenvironment (TME) modulation, and tumor promotion remain largely unknown. A series of computer‐aided bioinformatic analyses were conducted based on transcriptomic, single‐cell sequence, and spatial transcriptomic data to determine the m7G modification patterns in head and neck squamous cell carcinoma (HNSCC). Consensus clustering approach was employed according to the expressions of 33 m7G regulators. ESTIMATE, CIBERSORT, and single sample gene set enrichment analysis algorithms were adopted to investigate the immune cell infiltration features. A prognostic model named m7Gscore was established. Seurat, SingleR, and Monocle2 were used to analyze the single‐cell sequence profiling. STUtility was used to integrate multiple spatial transcriptomic datasets. Quantitative reverse transcription polymerase chain reaction, transwell, and wound‐healing assay were performed to verify the oncogenes. Here, three different m7G modification patterns were highlighted in HNSCC patients, which were also related to various clinical manifestations and three representative immunophenotypes: immune‐excluded, immune‐desert, and inflamed, separately. Patients with lower m7Gscore were highlighted by higher immune cell infiltrations, better overall survival rates, lesser tumor mutation burden (TMB), lower sensitivities to target inhibitors therapies, and better immunotherapeutic response. Moreover, DCPS, EIF4E, EIF4E2, LSM1, NCBP2, NUDT1, and NUDT5 were identified to play critical roles in T‐cell differentiation. Knockdown of LSM1/NUDT5 could restrain the malignancy of HNSCC cells. Collectively, quantitative assessment of m7G modification patterns in individual HNSCC patients could contribute to identifying more efficient immunotherapeutic approaches and improve the clinical outcome of HNSCC.