Associations of high-resolution-typing-defined MICA and MICB polymorphisms, and the levels of soluble MICA and MICB with Oral Squamous Cell Carcinoma in Bulgarian patients.

BACKGROUND Oral Squamous Cell Carcinoma (OSCC) is a malignancy characterized by an aggressive tumor growth and significant mortality. Clarifying mechanisms responsible for immunomodulation are among the main challenges for the development of personalized approaches for management of patients with OSCC. The aim of the present study was to analyze the relevance of MICA and MICB to OSCC pathogenesis focusing on allele polymorphisms and the levels of soluble MICA and MICB molecules. MATERIALS AND METHODS 73 patients diagnosed with OSCC and 149 healthy controls from the Bulgarian population were included in the study. MICA and MICB polymorphism was analyzed at allelic level using Next Generation Sequencing. Serum levels of soluble MICA and MICB molecules were measured by ELISA. RESULTS Our results show significant protective association with MICB*002:01, while relatively rare alleles MICB*018, *019 and *020 were observed with statistically significant increased frequency in OSCC patients compared to controls. Additionally, a predisposing association was observed for MICA*008:01-MICB*019 haplotype. A correlation analysis between functionally relevant MICA polymorphisms and sMICA showed that homozygosity for MICA-A5.1 or 129Val in OSCC patients was associated with significantly higher serum levels of sMICA. . CONCLUSION This is the first study showing significant associations between MICB alleles and OSCC and suggesting the possible role of MICB in immunosurveillance in OSCC development. Observed correlations between the levels of soluble MICA molecules and functionally relevant polymorphisms might represent a further step towards a better understanding of molecular mechanisms of OSCC and developing strategies for therapeutic targeting harnessing effective immunosurveillance.