title: 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 the prevention of colorectal cancer. Recent lines of evidence suggest 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 downregulation of MUC2 and MUC4 expression (p < 0.0001) while MUC1 and MUC5AC expressions 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. Glycan epitope-Tn/STn on MUC1 showed higher expression in hyperplastic polyps (p = 0.023), adenomas (p = 0.042) and adenocarcinomas (p = 0.0096) compared to normal tissues. 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.
authors.forename: Shiv Ram
authors.initials: SR
authors.lastname: Krishn
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA. Electronic address: skaur@unmc.edu.
authors.forename: Sukhwinder
authors.initials: S
authors.lastname: Kaur
authors.affiliation: Department of Biostatistics, College of Public Health, University of Nebraska Medical Center, Omaha, NE, USA.
authors.forename: Lynette M
authors.initials: LM
authors.lastname: Smith
authors.affiliation: Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, USA.
authors.forename: Sonny L
authors.initials: SL
authors.lastname: Johansson
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.
authors.forename: Maneesh
authors.initials: M
authors.lastname: Jain
authors.affiliation: Department of Surgery, University of Nebraska Medical Center, Omaha, NE, USA.
authors.forename: Asish
authors.initials: A
authors.lastname: Patel
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.
authors.forename: Shailendra K
authors.initials: SK
authors.lastname: Gautam
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA; Fred and Pamela Buffett Cancer Center, Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Hollingsworth
authors.affiliation: Department of Cellular and Molecular Medicine, Copenhagen Center for Glycomics, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Ulla
authors.initials: U
authors.lastname: Mandel
authors.affiliation: Department of Cellular and Molecular Medicine, Copenhagen Center for Glycomics, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Henrik
authors.initials: H
authors.lastname: Clausen
authors.affiliation: Department of Mathematics, City University of Hong Kong, Hong Kong.
authors.forename: Wing-Cheong
authors.initials: WC
authors.lastname: Lo
authors.affiliation: Department of Mathematics, University of Wisconsin, Madison, WI, USA.
authors.forename: Wai-Tong Louis
authors.initials: WT
authors.lastname: Fan
authors.affiliation: Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Upender
authors.initials: U
authors.lastname: Manne
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA; Fred and Pamela Buffett Cancer Center, Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, USA. Electronic address: sbatra@unmc.edu.
authors.forename: Surinder K
authors.initials: SK
authors.lastname: Batra
mesh_terms: D000236:Adenoma / Q000378:metabolism* / Q000473:pathology*; D014408:Biomarkers, Tumor / Q000378:metabolism; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D055088:Early Detection of Cancer; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D009077:Mucins / Q000378:metabolism*; D015999:Multivariate Analysis; D011134:Polysaccharides / Q000378:metabolism*; D011230:Precancerous Conditions / Q000378:metabolism / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D009077:Mucins; D011134:Polysaccharides
keywords: Adenoma; Colonic mucin; Colorectal cancer; Glycan; Hyperplastic polyp