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Background: The major histocompatibility complex class I-related chain A (MICA) molecules play a pivotal role in the modulation of anti-tumor immune responses. A polymorphic change from methionine (Met) to valine (Val) at amino acid position 129 of the alpha 2 heavy-chain categorize MICA alleles into strong and weak binders for the NKG2D receptor. We investigated here whether MICA-129 alleles are associated with gastro-intestinal tract (GItract) carcinomas in Tunisian affected patients as compared to healthy controls (HC). Material and methods: 181 patients affected by colorectal cancer (CRC) and 61 patients affected by gastric cancer (GC) along with 203 healthy controls (HC) were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) procedure. Results: We found that the MICA-129 Val/Val genotype was statistically more prevalent in patients affected both by CRC and GC as compared to HC. After stratification with poor prognostic parameters, we observed that MICA- 129 Val/Val genotype is significantly associated with advanced tumor extension (T3-T4), lymph node metastasis (N+), and distance metastasis (M+). In both cases, the MICA-129 Val/Val genotype seems to behave as a risk genotype and a poor prognostic biomarker in our population. Conclusion: Our findings suggest a potential tumor escape possibly due to an inability to activate NK cells and/ or to stimulate specific T lymphocytes subsets particularly active in the GI-tract.

MICAMICA-129 Met/Val Variant as Possible Biomarker of Diagnosis and Prognostic of Gastro-Intestinal Tract Carcinomas