Linking the Defect of Gamma-Aminobutyric Acid Type A Receptor Subunit Delta Gene to the Microsatellite Instability in Colorectal Cancer

Abstract

Abstract Introduction: There is primitive data suggest the role of gamma-aminobutyric acid type A receptor subunit delta (GABRD) in the pathogenesis of colorectal cancer. This research aimed to investigate the role of GABRD in patients with microsatellite instability (MSI)-associated colorectal cancer. Materials and Methods: In total, 58 patients diagnosed with MSI-associated adenocarcinoma of colorectal cancer participated in this study. The level of GABRD expression in both cancerous and noncancerous colonic and rectal tissue was done first by immunohistochemistry and then confirmed by quantitative real-time polymerase chain reaction (PCR). In addition, GABRD expression level was correlated with other pathologic parameters of patients. Results: Overall, 72.41% of cases expressed a high level of GABRD at the genetic level, and 67.24% expressed GABRD at the protein level. Moreover, the adjacent normal tissue did not show specific expression of GABRD protein by immunohistochemical analysis. Also, this study demonstrates a significant correlation between GABRD expression to the advanced stages of MSI-associated adenocarcinoma of colorectal cancer. Conclusion: GABRD can be a new and important diagnostic marker in patients with MSI and can be targeted for the treatment of patients with colorectal cancer having MSI. Further studies with larger sample sizes and in vitro studies will be of great value to uncover the pathway by which this gene controls the defect in mismatch repair (MMR) genes.