Expression of UDP-glucuronosyltransferase 1A, nuclear factor erythroid-E2-related factor 2 and Kelch-like ECH-associated protein 1 in colonic mucosa, adenoma and adenocarcinoma tissue

Abstract

We investigated the expression of UDP-glucuronosyl- transferase 1A (UGT1A), nuclear factor erythroid-E2-related factor 2 (Nrf2) and Kelch-like ECH-associated protein 1 (Keap1) in normal colonic mucosa, adenoma tissue and adenocarcinoma tissue, to analyze the correlation between their expression and the clinicopathological features of adenocarcinoma and their roles in colonic carcinogenesis. Using immunohistochemical analysis, we investigated the expression of UGT1A, Nrf2 and Keap1 in normal colonic mucosa (n=24), adenoma tissue (n=30) and adenocarcinoma tissue (n=77). We found that the positive rate of UGT1A was 83.3% in normal colonic mucosa, 80.0% in adenoma tissue and significantly lower, 53.2%, in adenocarcinoma tissue (normal colonic vs. adenoma tissue, P=0.071; normal colonic vs. adenocarcinoma tissue, P=0.023; adenoma vs. adenocarcinoma tissue, P=0.019). The expression levels of Nrf2 were high in adenoma and adenocarcinoma tissues, with positive rates of 70.0 and 87.0%, respectively, but were significantly lower in normal colonic tissue, with a positive rate of 41.7% (normal colonic vs. adenoma tissue, P=0.000; normal colonic vs. adenocarcinoma tissue, P=0.000; adenoma vs. adenocarcinoma tissue, P=0.000). The positive rate of Keap1 was 54.2% in normal mucosa, 70.0% in adenoma tissue and 61.0% in adenocarcinoma tissue (normal colonic mucosa vs. adenoma tissue, P=0.200; normal colonic vs. adenocarcinoma tissue, P=0.040; adenoma vs. adenocarcinoma, P=0.002). In addition, there was no correlation between the expression of Nrf2/Keap1 in adenoma and adenocarcinoma tissues (r=0.067, P=0.723; r=0.042, P=0.715, respectively). The results suggest that decreased expression of UGT1A and the dysregulation of the Nrf2/Keap1 system may be related to colonic carcinogenesis.