Expression analysis of aryl hydrocarbon receptor repressor (AHRR) gene in gallbladder cancer

Abstract

Background: The aryl hydrocarbon receptor repressor (AHRR), a member of the growing superfamily, is a basic helix-loop-helix/PerAHR nuclear translocator (ARNT)-Sim (bHLH-PAS) protein. AHRR has been proposed to function as a putative new tumor suppressor gene based on studies in multiple types of human cancers. This current study aims to investigate AHHR expression and its prognostic significance in gallbladder cancer. Methods: The study includes 48 gallbladder cancer and 34 chronic cholecystitis cases as controls. The expression level of AHRR was analyzed by using semi-quantitative PCR and immunohistochemical staining. The results were correlated with different clinical parameters. Results: We demonstrate that the expression of AHRR is significantly down-regulated in gallbladder cancer tissue samples as compared to that in chronic cholecystitis tissue samples by reverse transcriptase PCR (RT-PCR) ( P = 0.017) and immunohistochemistry analysis ( P = 0.002). Interestingly, our RT-PCR data revealed that AHRR mRNA expression is frequently down-regulated (45.8%; 22/48) in cases as compared to 14.7% (5/34) in controls. Similarly, immunohistochemical analysis data show significant down-regulation of AHRR expression in 77.1% (37/48) of gallbladder cancer cases than 44.1% (15/34) in controls ( P < 0.017). Reduced mRNA and protein expression is significantly associated with advanced T-stage ( P = 0.001), histological differentiation ( P = 0.001), and tumors with nodal metastasis ( P = 0.001). Decreased expression of AHRR is significantly associated with poor prognosis in gallbladder cancer patients. Conclusion: In conclusion, the present study suggests that low AHRR expression may be critical in gallbladder cancer development. Our data suggests that AHRR may act as a tumor suppressor gene and its expression profile may be useful as a diagnostic marker in gallbladder cancer.

AhRR methylation contributes to disease progression in urothelial bladder cancer

“…In this study, we found that muscle-invasiveness is significantly associated with higher AhRR percent methylation, hence a higher repression of its transcription. This is supported in the literature, where AhRR is suggested to play a key role in tumor suppression and the fact that the expression of AhRR is downregulated in various cancer tissues [39][40][41][42]. AhRR repression may contribute to aggressive tumorigenic phenotype, including increased migration and invasiveness, and reduced apoptosis in cancer cells [41].…”