Decreased H2B monoubiquitination and overexpression of ubiquitin-specific protease enzyme 22 in malignant colon carcinoma

Abstract

This study aimed to evaluate the expression of H2B monoubiquitination enzyme (uH2B) and ubiquitin-specific protease enzyme 22 (USP22) in colon carcinoma and establish a correlation between the expression of these enzymes and clinicopathological parameters. The modification levels of uH2B and USP22 in 20 noncancerous and 129 cancerous colon samples were studied by immunohistochemistry. We used a dual-rated semiquantitative method to classify the expression according to 3 levels and analyzed these results. uH2B was abundant in the normal colon epithelium, but its expression was decreased in colon cancers (P < .001); the uH2B modification level correlated with tumor differentiation (P < .001), lymph node metastasis (P = .017), distant metastasis (P = .036), and tumor stage (P = .039). The USP22 expression in colon carcinoma was higher than that in normal tissues (P = .007) and negatively correlated with the degree of differentiation (P = .006), invasion (P = .025), lymph node metastasis (P = .026), and tumor stage (P = .044). uH2B and USP22 expression negatively correlated (r = -0.401, P < .001). Patients with uH2B-negative and USP22-positive staining were found to have lower survival rates (30.737 ± 2.866 versus 51.667 ± 2.286 months, P < .001). Positive uH2B and negative USP22 expression remained a statistically significant prognostic indicator in a multivariate Cox regression analysis (hazard ratio, 2.557; 95% confidence interval, 1.043-6.269; P = .04). We conclude that uH2B displays differential staining patterns according to progressive stages of colon cancer, indicating that uH2B may play an important inhibitory role in carcinogenesis. Increased USP22 expression in colon cancer correlated with reduced uH2B expression, and this expression pattern may contribute to tumor progression.

Keywords: Colon carcinoma; Epigenetics; H2B monoubiqutination; Immunohistochemistry; USP22.