Mucins and associated glycan signatures in colon adenoma–carcinoma sequence: Prospective pathological implication(s) for early diagnosis of colon cancer

Abstract

Development of biomarkers that detect early stage resectable premalignant lesions of colon can provide critical aid in prevention of colorectal cancer. Recent evidences advocate the utility of mucin expression to predict malignant transformation of colon pre-neoplastic lesions. In this study, we investigated the combined expression of multiple mucins and mucin-associated glycans during the adenoma-carcinoma sequence of colon cancer progression. Further, we evaluated their applicability as markers for differentiating adenomas/adenocarcinomas from hyperplastic polyps. Immunohistochemical analyses performed on colon disease tissue microarrays revealed that MUC2, MUC4 expression were downregulated (p<0.0001) and MUC1, MUC5AC expression were upregulated (p=0.01) during adenoma-adenocarcinoma progression. Expression of MUC17 was downregulated in inflamed tissues compared to normal tissues, but its increased expression differentiated adenomas (p=0.0028) and adenocarcinomas (p=0.025) from inflammation. MUC1 specific glycan-Tn/STn-MUC1 showed higher expression in hyperplastic polyps (p=0.023), adenomas (p=0.042) and adenocarcinomas (p=0.0096) compared to normal. Multivariate regression analyses indicated that a combination of MUC2, MUC5AC, and MUC17 could effectively discriminate adenoma-adenocarcinoma from hyperplastic polyps. Altogether, a combined analysis of altered mucins and mucin-associated glycans is a useful approach to distinguish premalignant/malignant lesions of colon from benign polyps.

Abrogation of MUC5AC Expression Contributes to the Apoptosis and Cell Cycle Arrest of Colon Cancer Cells

“…12 In addition, the upregulated level of serum MUC5AC was assessed in biliary tract cancer, 13 and MUC1 and MUC5AC expression was also found to be overexpressed during colon cancer progression. 14 Although the clinical significance of mucins was identified in various cancers, the mechanism of its tumorigenetic role was not well understood. MUC1 cytoplasmic tail (MUC1-CT) could suppress the p53-dependent apoptotic response to DNA damage, coactivate p21 at the transcriptional level, and attenuate activation of Bax transcription to inhibit the activation of intrinsic apoptotic pathways in the genotoxic stress response.…”

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

“…MUC are usually expressed on the apical surfaces of normal glandular epithelial cells and luminal epithelial cells and have key functions in immunity, cell adhesion, and intracellular signaling [13]. Studies on the subcellular distribution of MUC and biochemical characteristics of malignant transformation and progression implicate MUC in tumorigenesis and metastasis [14][15][16][17][18], suggesting that abnormal MUC expression may be a predictive biomarker of CRC.…”

MUC1, MUC2, MUC4, MUC5AC, Cdx2: immunohistochemical characteristics in polyps and adenocarcinoma of distal colon

“…По данным S. R. Krishn et al (2016), экспрессия MUC4 снижается в гиперпластических полипах, в еще большей мере -в зубчатых аденомах. Авто-ры предложили использовать данный маркер для дифференциальной диагностики этих полипов [5].…”