Abstract
The interleukin-1 (IL-1) signaling pathway plays a crucial role in mediating inflammatory responses by activating immune cells, with implications for various pathologies. In oral squamous cell carcinoma (OSCC), the role of IL-1 receptor antagonist (IL-1RA) and its isoforms remains poorly understood, with evidence suggesting context-dependent variations in their function. This study aimed to evaluate the immunoexpression of IL-1 signaling pathway in OSCC tissues and correlate these findings with clinicopathological prognostic factors. Clinicopathological data, including patient age, sex, tumor size, lymph node involvement, histological grade, and tumor stage, were evaluated. Hematoxylin and eosin-stained sections were reviewed for differentiation grade, tumor budding, perineural invasion, and the presence of adequate tumor tissue in the invasive front. Non-dysplastic adjacent epithelium (NDAE) from the same samples served as the control. Immunohistochemical analysis was performed against IL-1α, IL-1β, IL-1R1 and IL-1RA; staining was evaluated using the total tissue expression of each marker obtained with an ImageJ segmentation plugin. This study analyzed 44 OSCC cases, with most tumors in advanced stages (63.6%) and a five-year overall survival (OS) rate of 54.4%. Immunohistochemical analysis showed significant overexpression of IL-1α, IL-1β, IL-1R1, and IL-1RA in OSCC compared to NDAE (p < 0.0001). High IL-1RA expression was associated with tumor recurrence (p = 0.030) and poorer OS (p = 0.018) and disease-specific survival (DSS) (p = 0.028). Multivariate analysis identified IL-1RA overexpression (p = 0.007) and lymph node metastasis (p = 0.002) as independent risk factors for poor OS. High IL-1RA expression is associated with features of OSCC progression and adverse clinical outcomes. Further studies are needed to elucidate the mechanistic roles of IL-1RA and other IL-1 family members in OSCC.