Basic Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 28, 2018; 24(36): 4164-4177
Published online Sep 28, 2018. doi: 10.3748/wjg.v24.i36.4164
Differential expression of mucin 1 and mucin 2 in colorectal cancer
Aldona Kasprzak, Elżbieta Siodła, Małgorzata Andrzejewska, Jacek Szmeja, Agnieszka Seraszek-Jaros, Szczepan Cofta, Witold Szaflarski
Aldona Kasprzak, Elżbieta Siodła, Małgorzata Andrzejewska, Witold Szaflarski, Department of Histology and Embryology, Poznan University of Medical Sciences, Poznan 60-781, Poland
Jacek Szmeja, Chair and Department of General Surgery, Endocrinological and Gastroenterological Oncology, Poznan University of Medical Sciences, Poznan 60-355, Poland
Agnieszka Seraszek-Jaros, Department of Bioinformatics and Computational Biology, Chair of Clinical Pathomorphology, Poznan University of Medical Sciences, Poznan 60-529, Poland
Szczepan Cofta, Department of Pulmonology, Allergology and Respiratory Oncology, Poznan University of Medical Science, Poznan 60-569, Poland
Author contributions: Kasprzak A contributed to conception, design of the study, analyzed data and coordinated the research; Siodła E and Andrzejewska M performed the majority of immunohistochemical and molecular investigations; Szmeja J, Cofta S and Szaflarski W interpreted the data, analyzed the results, and performed a critical revision of the manuscript; Szmeja J provided samples of cancer patients and clinical data; Seraszek-Jaros A performed biostatistics and analyzed the data; Kasprzak A and Szaflarski W drafted the manuscript.
Supported by National Science Center in Poland, No. 2015/17/B/NZ7/03043.
Institutional review board statement: This study was approved by Committee on Bioethics of Poznan University of Medical Sciences, No. 924/14.
Conflict-of-interest statement: The authors have no conflicts of interest, including no conflicts concerning employment, consultancies, stock ownership, honoraria, paid expert testimonies, patent applications/registrations, grants or other funding.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Aldona Kasprzak, MD, PhD, Professor, Department of Histology and Embryology, Poznan University of Medical Sciences, Swiecicki Street 6, Poznan 60-781, Poland. akasprza@ump.edu.pl
Telephone: +48-61-8546441 Fax: +48-61-8546440
Received: July 16, 2018
Peer-review started: July 16, 2018
First decision: July 24, 2018
Revised: August 15, 2018
Accepted: August 24, 2018
Article in press: August 24, 2018
Published online: September 28, 2018
Processing time: 74 Days and 17.3 Hours
Abstract
AIM

To determine tissue expression (mRNA, protein) of two types of mucins [mucin 1 (MUC1) and mucin 2 (MUC2)] in patients with colorectal cancer (CRC).

METHODS

Expression of membrane-bound mucin (MUC1) and secretory mucin (MUC2) in CRC (mRNA, protein) were analyzed in tissue material including fragments of tumors obtained from CRC patients (n = 34), and fragments of normal colorectal tissue from the same patients (control). The analysis was conducted using real-time quantitative polymerase chain reaction (RT-qPCR) (transcripts), immunohistochemistry (IHC) (apomucins), and the modern approach for morphometric analysis of IHC reaction (HSV filter software). Results on tissue expression of both mucins (mRNA, protein) were compared to histological alterations in colorectal cancer samples and correlated with selected clinical data in the patients. The statistical analysis was conducted using Statistica PL v. 12.0 software.

RESULTS

Significantly higher expression of the MUC1 mRNA in the CRC, compared with the control and the borderline correlation of mRNA expression with MUC1 protein levels in colorectal samples was observed. The expression of apomucins concerned cell membranes (MUC1) and cytoplasm (MUC2) and occurred both in control tissues and in most cancerous samples. There were no significant relationships between MUC1 (mRNA, protein) and the clinicopathological data of patients. MUC2 protein expression was significantly lower as compared to the control, while MUC2 mRNA expression was comparable in both groups. The MUC1/MUC2 ratio was significantly higher in CRC tissues than in the control. The higher expression of MUC2 was a feature of mucinous CRC subtypes, and characterized higher histological stage of tumors. Negative correlations have been obtained between MUC2 and the Ki-67 antigen, as well as between MUC2 and p53 protein expressions in CRC.

CONCLUSION

A combination of tissue overexpression of MUC1, reduced MUC2 expression, and high ratio of MUC1/MUC2 is a factor of poor prognosis in CRC patients. MUC2 tissue expression allows to differentiate mucinous and nonmucinous CRC subtypes.

Keywords: Mucins; Real-time quantitative polymerase chain reaction; Colorectal cancer; Immunohistochemistry; HSV filter program

Core tip: Colorectal cancers (CRC) represent the second most widely manifested malignant tumor worldwide in women and third in men. The evident expression of two mucins [mucin 1 (MUC1) and mucin 2 (MUC2)] occurs in a normal and cancerous large intestine. Using RT-qPCR analysis and immunohistochemistry we confirmed higher expression of the MUC1 mRNA, lower MUC2 protein, and higher MUC1/MUC2 expression ratio in CRC samples as compared to the control. MUC2 protein expression correlates with increased cellular proliferation. A combination of tissue overexpression of MUC1, reduced MUC2 expression, and high ratio of MUC1/MUC2 may be a useful factor of poor prognosis in CRC patients.