Prognostic and Clinicopathological Significance of MUC Family Members in Colorectal Cancer: A Systematic Review and Meta-Analysis

Abstract

Objective. To assess the association between MUC expression levels in colorectal cancer (CRC) tissues and prognosis and investigate the associations between MUC expression levels and CRC clinicopathological characteristics. Methods. The PubMed, Embase, Cochrane Library, and Web of Science databases were searched from inception through September 13, 2019, to identify studies investigating the association between MUC expression levels in CRC tissues and prognosis. Pooled hazard ratios (HRs) or odds ratio (ORs) with 95% confidence intervals (CIs) were used to evaluate associations between MUC expression levels and prognosis or clinicopathological characteristics, respectively. The heterogeneity between studies was assessed by the I2 values, whereas the likelihood of publication bias was assessed by Egger’s linear regression and Begg’s rank correlation test. Results. Among 33 included studies (n=6032 patients), there were no associations between combined MUC phenotype expression levels and overall survival (OS) or disease-free survival (DFS)/relapse-free survival (RFS) in patients with CRC. In subgroup analyses, the upregulated MUC1 expression (HR=1.50; 95% CI, 1.29–1.74; P<0.00001) was associated with poor OS. However, the upregulated MUC2 expression (HR=0.64; 95% CI, 0.52–0.79; P<0.00001) was associated with better OS. Furthermore, a high level of MUC1 expression (HR=1.99; 95% CI, 0.99–3.99; P=0.05) was associated with shorter DFS/RFS. However, patients with a low level of MUC2 tumors showed better DFS/RFS than patients with a high level of MUC2 tumors (HR=0.71; 95% CI, 0.49–1.04; P=0.08; P=0.0.009, I2=67%) and MUC5AC expression (HR=0.56; 95% CI, 0.38–0.82; P=0.003) was associated with longer DFS/RFS. In addition, a high level of MUC1 expression was associated with CRC in the rectum, deeper invasion, lymph node metastasis, distant metastasis, advanced tumor stage, and lymphatic invasion. A high level of MUC2 expression had a protective effect. High secretion of MUC5AC is associated with colon cancer compared with rectal cancer. Conclusion. The protein expression of MUC1 might be a poor biomarker in colorectal cancer and might play a role in tumor transformation and metastasis. However, the protein expression of MUC2 expression might have a protective effect. Furthermore, randomized controlled trials (RCTs) of large patients are needed to confirm the results.

Galectin‑9 suppresses the tumor growth of colon cancer in vitro and in vivo

“…Currently, CRC treatment is mainly based on surgical removal of tumor tissue, chemotherapy, and radiotherapy, with the recent addition of immunotherapy (34). However, the overall survival rate of advanced CRC patients remains poor (35). Thus, there is a strong demand for new therapeutic approaches to CRC therapy.…”

MUC1 and MUC5AC implication in Tunisian colorectal cancer patients

“…In literature, the high expression of MUC1 positively correlates with stage, metastasis, poor tumor differentiation, and worse long-term survival [10,[26][27][28][29].…”

Elevated MUC5AC expression is associated with mismatch repair deficiency and proximal tumor location but not with cancer progression in colon cancer

“…This is in the lower range of data from previous studies. A total of 23 studies have earlier analyzed MUC5AC expression in colorectal cancer (Table 5 ) and described MUC5AC expression to occur in 0–95% analyzing 22–649 cancers [ 11 , 12 , 15 – 35 ]. Likely reasons for discrepant results include the use of different antibodies, IHC protocols, and cut-off levels or scores to define MUC5AC positivity as well as the composition of the tumor cohorts.…”

“…However, multiple studies have provided evidence that MUC5AC expression may drive cancer aggressiveness in colorectal cancer cell lines and xenograft models [37][38][39]. The 11 studies analyzing the prognostic relevance of MUC5AC expression in colorectal cancer in cohorts of 35-649 patients have found divergent results [11,12,17,18,20,21,23,25,31,34,35].…”

“…MUC5AC is a secreted gel-forming mucin [ 6 , 7 ] expressed in normal mucus-producing cells of the stomach, the lung, and the uterine cervix [ 8 – 10 ] as well as in cancer cells of the ovarian, the pancreas, and the gastrointestinal tract [ 11 – 14 ]. MUC5AC expression was earlier described to occur in 0–95% of colorectal cancers in studies analyzing 22–649 cancers [ 11 , 12 , 15 – 35 ], and it was shown to be linked to MSI or dMMR in studies analyzing 35–649 cancers [ 16 – 18 , 20 , 22 , 26 , 28 , 30 , 33 , 34 ]. Since MSI is linked to favorable prognosis in colorectal cancer [ 36 ], a favorable disease course could be expected in MUC5AC-positive cancers.…”