Differential expression of mucin 1 and mucin 2 in colorectal cancer

World J Gastroenterol. 2018 Sep 28;24(36):4164-4177. doi: 10.3748/wjg.v24.i36.4164.

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

Publication types

  • Comparative Study

MeSH terms

  • Adenocarcinoma, Mucinous / mortality
  • Adenocarcinoma, Mucinous / pathology*
  • Adenocarcinoma, Mucinous / surgery
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology*
  • Colorectal Neoplasms / surgery
  • Female
  • Humans
  • Intestine, Large / pathology
  • Male
  • Middle Aged
  • Mucin-1 / analysis
  • Mucin-1 / genetics
  • Mucin-1 / metabolism*
  • Mucin-2 / analysis
  • Mucin-2 / genetics
  • Mucin-2 / metabolism*
  • Neoplasm Staging
  • Prognosis
  • RNA, Messenger / metabolism
  • Survival Rate

Substances

  • Biomarkers, Tumor
  • MUC1 protein, human
  • MUC2 protein, human
  • Mucin-1
  • Mucin-2
  • RNA, Messenger