Integrated Analysis of OX40/OX40L Genetic Variants and Circulating Soluble Immune Checkpoint Markers in Laryngeal Cancer Recurrence

Abstract

Objective: Laryngeal cancer is an aggressive malignancy in which immune regulatory mechanisms play a critical role in tumor progression and recurrence. The OX40/OX40L axis, a member of the tumor necrosis factor superfamily, has been implicated in immune modulation however, its genetic and soluble profiles in laryngeal cancer remain insufficiently characterized. Beyond cancer susceptibility, the clinical relevance of OX40/OX40L alterations in recurrence biology remains poorly understood.\Materials and Methods: In this study, we investigated the distribution of OX40 rs17568 and OX40L rs1234313 polymorphisms and evaluated their association with serum soluble OX40 (sOX40) and OX40L (sOX40L) levels in 80 patients with laryngeal cancer and 111 healthy controls. Genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR--RFLP), and soluble protein levels were quantified by enzyme-linked immunosorbent assay (ELISA).\Results: No significant differences in serum sOX40 or sOX40L levels were observed between patients and controls. While OX40 rs17568 genotype distributions were comparable between groups, a significant difference was detected for OX40L rs1234313, with homozygous genotypes (AA and GG) being more frequent in laryngeal cancer patients (p=0.007). Although genotype distributions were not associated with clinicopathological parameters, circulating sOX40 levels were significantly higher in patients with disease recurrence than in those without recurrence (p=0.008).\Conclusion: The findings suggest that alterations in the OX40/OX40L axis may be associated with immune dysregulation during disease progression rather than cancer initiation in laryngeal cancer. Particularly, elevated circulating sOX40 levels were associated with disease recurrence. Given the cross-sectional and exploratory nature of the study, these findings should be interpreted with caution and require validation in larger prospective cohorts.