Prognostic Value of MUC2 Expression in Colorectal Cancer: A Systematic Review and Meta-Analysis

Abstract

Background The reliability of MUC2 as a prognostic marker in colorectal cancer (CRC) is controversial. This study evaluated the association between MUC2 expression levels in CRC tissues and prognosis. Methods The PubMed, Web of Science, Embase, Cochrane Library, China Biology Medicine disc (CBMdisc), Wanfang Database, and China National Knowledge Infrastructure (CNKI) databases were searched to identify studies exploring the relationship between MUC2 expression in CRC tissues and overall survival (OS). Pooled hazard ratios (HRs) and risk ratios (RRs) with 95% confidence intervals (CIs) were used to evaluate the associations between MUC2 expression levels and prognosis and MUC2 expression levels and CRC clinicopathological characteristics, respectively. Results The meta-analysis included 11 studies (2619 patients). Low MUC2 expression level was significantly associated with poor OS (HR, 1.67; 95% CI, 1.43–1.94; P < 0.00001) and disease-free survival (DFS)/recurrence-free survival (RFS) (HR, 1.60; 95% CI, 1.21–2.12; P = 0.001) in patients with CRC. Low MUC2 expression level was associated with advanced TNM stage (RR, 1.42; 95% CI, 1.26–1.60; P < 0.00001), lymph node metastasis (RR, 1.41; 95% CI, 1.25–1.60; P < 0.00001), lymphatic invasion (RR,1.64; 95% CI, 1.26–2.12; P = 0.0002), rectal tumor site (RR, 1.26; 95% CI, 1.09–1.46; P = 0.001), and large tumor size (RR,1.32; 95% CI, 1.02–1.70; P = 0.03). There were no associations between low MUC2 expression level and gender, histological grade, depth of invasion, and distant metastasis. Conclusion The low levels of MUC2 in CRC tissues are poor prognostic factor independent of stage or other well-recognized markers of later-stage disease. Large well-designed cohort studies are required to validate MUC2 as a biomarker for poor prognosis in CRC.

The Diverse Roles of the Mucin Gene Cluster Located on Chromosome 11p15.5 in Colorectal Cancer

“…Moreover, transcription factors also play different roles in the regulation of MUC gene expression. For example, the Notch/Hath1 axis transcriptionally regulates the expression of MUC6 and MUC5AC genes (Li et al, 2018), while the transcription factors Sp1, SOX9, and CDX2 can participate in the transcriptional regulation of many MUC genes, including MUC2 (Sakai et al, 2005). Furthermore, mutations of tumor suppressor genes, such as p53 and RAS, are involved in the regulation of MUC genes located on chromosome 11p15.5 (Ookawa et al, 2002).…”

“…Correlation analysis of MUC expression and clinicopathological parameters of patients with CRC found that MUC2 and MUC5AC were correlated with tumor stage, lymph node metastasis and prognosis of patients, and could be used as biomarkers to evaluate the prognosis of patients (Li et al, 2018), while the overexpression of MUC5B in CRC cells seemed to be related to degree of malignancy (Walsh et al, 2013), and increased expression of MUC6 was associated with malignancy and poor prognosis in CRC cells (Betge et al, 2016). Based on the current findings, the detection of MUC expression in CRC patients will benefit patients in the following aspects.…”

“…By analyzing the relationship between MUC2 expression and clinicopathological parameters in patients with colorectal cancer, Li et al (2018) found that MUC2 expression was negatively correlated with TNM stage and lymphatic metastasis, but positively associated with survival. However, in the Finland population, Elzagheid et al (2013) reported the correlation of MUC2 expression with the location of the tumor, recurrence, and prognosis of CRC.…”

Mucins and their receptors in chronic lung disease

“…MUC6 expression is also reduced in gastric cancers and is an independent predictor for malignant progression . MUC2 is the major structural component of colonic mucosa and has been associated with colorectal cancer, where its reduced expression results in increased inflammation and promotes IL‐6‐induced epithelial to mesenchymal transition …”

“…70 MUC2 is the major structural component of colonic mucosa and has been associated with colorectal cancer, where its reduced expression results in increased inflammation and promotes IL-6-induced epithelial to mesenchymal transition. 71 The CA125 antigen is a well-recognised marker for ovarian cancer and corresponds to the cleaved extracellular TR region of MUC16. Mutations of MUC16 have also been associated with air pollution-related lung cancer.…”