Diverse expression patterns of mucin 2 in colorectal cancer indicates its mechanism related to the intestinal mucosal barrier

Abstract

BACKGROUND Abnormal expression patterns of mucin 2 (MUC2) have been reported in a variety of malignant tumors and precancerous lesions. Reduced MUC2 expression in the intestinal mucosa, caused by various pathogenic factors, is related to mechanical dysfunction of the intestinal mucosa barrier and increased intestinal mucosal permeability. However, the relationship between MUC2 and the intestinal mucosal barrier in patients with colorectal cancer (CRC) is not clear. AIM To explore the relationship between MUC2 and intestinal mucosal barrier by characterizing the multiple expression patterns of MUC2 in CRC. METHODS Immunohistochemical staining was performed on intestinal tissue specimens from 100 CRC patients, including both cancer tissues and adjacent normal tissues. Enzyme-linked immunosorbent assays were performed on preoperative sera from 66 CRC patients and 20 normal sera to detect the serum levels of MUC2, diamine oxide (DAO), and D-lactate (D-LAC). The relationship between MUC2 expression and clinical parameters was calculated by the χ 2 test or Fisher’s exact test. Prognostic value of MUC2 was evaluated by Kaplan-Meier curve and log-rank tests. RESULTS Immunohistochemical staining of 100 CRC tissues showed that the expression of MUC2 in cancer tissues was lower than that in normal tissues (54% vs 79%, P < 0.05), and it was correlated with tumor-node-metastasis (TNM) stage and lymph node metastasis in CRC patients ( P < 0.05). However, the serum level of MUC2 in CRC patients was higher than that in normal controls, and was positively associated with serum levels of human DAO ( χ 2 = 3.957, P < 0.05) and D-LAC ( χ 2 = 7.236, P < 0.05), which are the biomarkers of the functional status of the intestinal mucosal barrier. And the serum level of MUC2 was correlated with TNM stage, tumor type, and distant metastasis in CRC patients ( P < 0.05). Kaplan-Meier curves showed that decreased MUC2 expression in CRC tissues predicted a poor survival. CONCLUSION MUC2 in tissues may play a protective role by participating in the intestinal mucosal barrier and can be used as an indicator to evaluate the prognosis of CRC patients.

An Increase in Mucin2 Expression Is Required for Colon Cancer Progression Mediated by L1

“…The intestinal mucus layer consists mainly of Mucin2, a major mucin synthesized and secreted by goblet cells [19][20][21]. It comprises most of the secreted mucinous proteins around the colon cancer tissue [22][23][24] and plays a crucial role in forming the mucinous layer around the normal colonic epithelium that protects it from pathogens and mechanical insults [25][26][27][28]. The altered expression of Mucin2 is often a characteristic feature of colon cancer progression [16,29,30].…”