Identification of biomarkers related to neutrophil mitochondrial dysfunction in oral squamous cell carcinoma based on single-cell and bulk RNA sequencing

Oral squamous cell carcinoma (OSCC) is a common malignant tumor of the head and neck. Tumor-associated neutrophils are recruited to tumor lesions upon tumor stimulation and drive OSCC progression, yet the functional characteristics of neutrophils and the specific role of mitochondrial metabolism in the development and progression of OSCC remain unclear. Through single-cell RNA sequencing (scRNA-seq), mitochondria-related key neutrophil subpopulations were identified in OSCC. Based on key neutrophil subpopulations, key genes associated with mitochondria were subsequently screened via differential expression analysis. Survival analysis was performed for these key genes, and their expression was validated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Subsequently, the potential molecular mechanisms of biomarker were revealed by enrichment analysis and immune infiltration analysis. In this study, neutrophils were divided into 4 cell subpopulations, among which the emNeu subpopulation exhibited the highest MRGs score and was thus defined as key neutrophil subpopulation. Low expression of mitochondrial-related genes ATP6V1E1, COX5A, HADHB, and SKA2 was significantly associated with better survival probability. Among these, the expression pattern of ATP6V1E1 was consistent with the results of bioinformatics analysis, which were significantly up-regulated in OSCC. Therefore, ATP6V1E1 was identified as potential biomarker of OSCC. Enrichment analysis demonstrated that ATP6V1E1 participates in the progression of OSCC through energy metabolism, cell proliferation, and lipid metabolism. Immune infiltration analysis revealed neutrophils were significantly downregulated in the high-expression of ATP6V1E1 patients. In summary, this study confirmed that emNeu were the key neutrophil subpopulations in OSCC, and identified ATP6V1E1 as potential biomarker for OSCC.