Clinical implications of the MHC class I chain-related A (MICA) variants in gastric adenocarcinoma.


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Karen Toledo, Carolina Ribeiro, María Andrea Canals, Patricio González, Valentina Garate, Ricardo Armisen, Maria Carmen Molina

Abstract

Background

Gastric adenocarcinoma (GA) epithelial cells express the MICA protein, a ligand to NKG2D receptor that triggers natural killer (NK) cells effector functions for early tumor elimination. The MICA gene is highly polymorphic, originating alleles that encode protein variants with a controversial role in cancer. The main goal of this work is to investigate the clinical significance of the MICA variants in GA.  

Method

We included 37 patients over 18 years with GA from Gastroenterology Surgery Department at Salvador Hospital, Metropolitana Region, Chile and 50 healthy volunteers over 18 years without prior gastrointestinal diseases or some type of cancer. We obtained a blood sample to extract genomic DNA.  To identify the MICA alleles, we analyzed the samples by PCR-Sequencing based typing (PCR-SBT).

Results

The analysis of MICA gene sequence allowed to identify both 13 MICA-sequence and 5 MICA-STR alleles in the studied population. The results showed that allele frequencies of MICA were different in GA patients in comparison to healthy volunteers (p=0.024). We identified that the most frequent allele both in patients as volunteers was the MICA*002 allele (STR-A9), which was followed by the MICA*008 allele (STR-A5.1). We found that the MICA*009 allele frequency was significantly higher in patients than healthy volunteers (p=0.007) with a OR: 5.11  (95% CI: 1.39-18.74,  p=0.014).  The regression analysis indicated that the presence of MICA*009 increases the average probability of gastric cancer in 39% (95% CI: 0.10-0.68).  According the survival analysis,  MICA*002/002 and MICA*002/004 patients showed a higher survival than MICA*002/008 patients (p=0.014) and MICA*002/009 (p=0.040). 

Conclusion

In conclusion, our findings suggest that the presence of MICA*009 increases the probability of GA, and MICA*002 patients would have a better survival. The studying of MICA alleles is crucial to explain the immune-evasion mechanisms and improve the therapies.  

Impact statement

These findings could be useful to the evaluation of risk and prognosis of GA and personalize the therapy.