AARS1 Implicates Malignancy and Immune Infiltration in Head and Neck Squamous Cell Carcinoma, Serving as a Prognostic Predictor

ABSTRACT Background The aberrant expression of AARS1 has been linked to tumor progression in various cancers. However, its role and underlying mechanisms in head and neck squamous cell carcinoma (HNSCC) remain unclear. Methods We validated AARS1 expression using databases and cell lines. Prognostic significance was assessed via Kaplan–Meier and Cox analyses. CCK‐8, colony formation, wound healing, and flow cytometry evaluated the effects of AARS1 on HNSCC malignancy. Immune cell infiltration and immune checkpoint associations with AARS1 were analyzed using TIMER, CIBERSORT, MCPCOUNTER, and QUANTISEQ. Subsequently, histological staining and western blotting were performed to verify the identified relationship between AARS1 and immune suppression in HNSCC. Results AARS1 was significantly upregulated in HNSCC tissues and cell lines. High AARS1 expression predicted poor overall survival (OS), disease‐specific survival (DSS), and progression‐free interval (PFI). Silencing AARS1 inhibited cell proliferation, migration, and resistance to apoptosis. In the AARS1 high‐expression group, decreased CD8 + T cell infiltration was observed, along with increased expression of Siglec‐15 and ITPRIPL1. These findings suggest that AARS1 might contribute to immune evasion and tumor progression in HNSCC. Conclusion Elevated AARS1 expression correlates with poor prognosis, malignant behaviors, and immune infiltration in HNSCC, indicating that AARS1 may serve as a potential therapeutic target.