ABSTRACT
Gastric cancer (GC) is a serious fatal cancer on a global scale because of its presentation at advanced stage. The expressions of vascular endothelial growth factor (VEGF), E-cadherin, and matrix metalloproteinases (MMPs) in other cancers have been reported. However, its expression and underlying mechanisms are little known in gastric cancer in Indian context. In this study, we detected mRNA expression of VEGF, E-cadherin, and MMPs (MMP-1, MMP-2, and MMP-9) in 73 gastric cancer tissues and 27 normal controls by reverse-transcriptase polymerase chain reaction (RT-PCR). Receiver operator characteristics analysis was done for determining the diagnostic utility of VEGF, MMPs and E-cadherin with respect to the sensitivity and specificity. The association of VEGF, MMPs, and E-cadherin expression with the clinicopathological characteristics and the prognosis was subsequently analyzed. The mRNA expression results showed that E-cadherin was significantly downregulated in 47.9% of GC in comparison to control. There was no change in VEGF expression observed in 90.4% GC cases. MMP-1, MMP-2, and MMP-9 were overexpressed in 13.7%, 28.8%, and 11% of GC, respectively, with significant change in MMP-2 (p ≤ 0.0001) and MMP-9 (p = 0.027) in comparison to control. Our results strengthen the necessity of more studies to elucidate the prophetic role of these genes in the development of gastric 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.
