Protein expression trends of DNMT1 in gastrointestinal diseases: From benign to precancerous lesions to cancer

BACKGROUND: In recent years, the incidence of gastrointestinal (GI) cancer in China has increased annually. Early detection and appropriate therapy are considered to be the key to treat GI cancer. DNMT1 takes an active part in the advancement of GI cancer, which will change as the disease progresses. But its expression characteristics in the dynamic variations of GI carcinogenesis are still unclear. AIM: To investigate the expression characteristics of DNMT1 in different GI diseases. METHODS: We detected the expression of DNMT1 in 650 cases of different GI diseases by immunohistochemistry, including 90 cases of chronic superficial gastritis (CSG), 72 cases of atrophic gastritis with intestinal metaplasia (AG/GIM), 54 cases of low-grade intraepithelial neoplasia (GLIN), 66 cases of high-grade intraepithelial neoplasia (GHIN), 71 cases of early gastric cancer (EGC), 90 cases of normal intestinal mucosa (NIM), 54 cases of intestinal low-grade intraepithelial neoplasia (ILIN), 71 cases of intestinal high-grade intraepithelial neoplasia (IHIN), and 82 cases of early colorectal cancer (ECRC). RESULTS: In the CSG group, all cases showed weakly positive or negative expression of DNMT1. However, in other four groups (AG/GIM, GLIN, GHIN, and EGC), the positive expression rate gradually increased with the severity of the diseases; the negative or weakly positive cases accounted for 55.56% (40/72), 38.89% (21/54), 1.52% (1/66), and 1.41% (1/71), respectively. Besides, the moderately positive cases were 44.44% (32/72), 57.41% (31/54), 80.30% (53/66), and 43.66% (31/71), respectively. The strongly positive cases only existed in the GLIN (3.70%, 2/54), GHIN (18.18%, 12/66), and EGC (54.93%, 39/71) groups. The differences between any two groups were statistically significant (P < 0.05). Similarly, in the NIM group, cases with weakly positive expression of DNMT1 were predominant (91.11%, 82/90), and the rest were moderately positive cases (8.89%, 8/90). In the ILIN, IHIN, and ECRC groups, the rates of cases with weak or negative expression of DNMT1 were 46.30% (25/54), 12.68% (9/71), and 4.88% (4/82), respectively; with moderately positive expression were 53.70% (29/54), 71.83% (51/71), and 34.15% (28/82), respectively; and with strongly positive expression were 0.00% (0/54), 15.49% (11/71), and 60.98% (50/82), respectively. The differences between any two groups were also statistically significant (P < 0.05). CONCLUSION: The overexpression of DNMT1 protein could effectively predict early GI cancers and severe precancerous lesions, which may have potential clinical application value.