The Mucin Family of Proteins: Candidates as Potential Biomarkers for Colon Cancer

Abstract

Mucins (MUC1-MUC24) are a family of glycoproteins involved in cell signaling and barrier protection. They have been implicated in the progression of numerous malignancies including gastric, pancreatic, ovarian, breast, and lung cancer. Mucins have also been extensively studied with respect to colorectal cancer. They have been found to have diverse expression profiles amongst the normal colon, benign hyperplastic polyps, pre-malignant polyps, and colon cancers. Those expressed in the normal colon include MUC2, MUC3, MUC4, MUC11, MUC12, MUC13, MUC15 (at low levels), and MUC21. Whereas MUC5, MUC6, MUC16, and MUC20 are absent from the normal colon and are expressed in colorectal cancers. MUC1, MUC2, MUC4, MUC5AC, and MUC6 are currently the most widely covered in the literature regarding their role in the progression from normal colonic tissue to cancer.

Keywords: adenocarcinoma; adenoma; adenomatous polyps; colorectal cancer; hyperplastic polyps; mucinous carcinoma; mucins; prognostics; serrated polyps.

Figure 3

Orthotopic model of LS174T labeled with MUC4-IR800 reported by Turner et al., The American Journal of Surgery 2022, reprinted with permission [81]. (A) Bright light image of an LS174T tumor growing from the cecum. (B) Fluorescence imaging of MUC4-IR800 brightly labelling a cecal tumor. Yellow arrows: tumor. Scale: 1 cm.

Figure 4

IHC of MUC5AC and MUC5B from Krishn et al., Cancer Letters 2016, reprinted with permission [61]. (A) No MUC5AC staining was present within the normal colon. (B–D) Increased MUC5AC expression was seen in hyperplastic polyps, adenomas, and adenocarcinoma. (E) No MUC5B staining was seen within the normal colon. (F–H) Rare instances of MUC5B expression were seen in hyperplastic polyps, adenomas, and adenocarcinoma.

Figure 1

Immunohistochemistry of MUC2 from Wang et al., Oncology Letters 2017, reprinted with permission [56]. (A) Cytoplasmic MUC2 staining in normal colon. (B) Minimal to no staining within carcinoma. Magnification 200x.

Figure 2

IHC of MUC4 from Shanmugam et al., Cancer 2010, reprinted with permission [78]. (A) MUC4 staining was noted in crypts of the normal colon. (B) Strong cytoplasmic staining within CRC. (C) Weak staining of CRC compared to adjacent normal tissue. Thin arrows—normal colonic epithelium; thick arrows—CRC. Scale: (A) 200 μm; (B) 600 μm; (C) 200 μm.

Figure 5

IHC of MUC16 and MUC16 from Streppel et al., Human Pathology 2012, reprinted with permission [111]. (A) No MUC16 staining was seen in an adenoma with low-grade dysplasia. (B) Focal and (C) Diffuse MUC16 staining within carcinoma samples. Magnification: (A) 10x; (B,C) 20x.