Differential membranous E-cadherin expression, cell proliferation and O-GlcNAcylation between primary and metastatic nodal lesion in colorectal cancer

Introduction: O-GlcNAcylation is an O-linked beta-N-acetylglucosamine (O-GlcNAc) moiety linked to the side chain hydroxyl of a serine or threonine residue. The E-cadherin/beta-catenin system, an integral component of epithelial to mesenchymal transition (EMT)/mesenchymal to epithelial transition (MET), is affected through O-GlcNAcylation. The current study examined the status of EMT/MET in both the tumor center and invasive front of the primary colorectal carcinoma (CRC) and metastatic nodal lesions, which were compared to O-GlcNAcylation expression levels in those areas. In addition, the cliniopathological significance of O-GlcNAcylation was studied Material and methods: Immunohistochemical staining for E-cadherin, P-catenin, Snail, O-GlcNAc and Ki67 was performed in 40 primary CRC tissues, 40 nonneoplastic colons, and 17 nodal metastatic lesions. Western blot was also conducted in primary CRC tissue Results: Membranous E-cadherin expression was lowest in the invasive front, but showed greater increases in metastatic nodal lesions. Moreover, its expression level was negatively correlated with that of nuclear p-catenin and Snail. The Ki67 labeling index (LI) was lowest in the invasive front, and increased in metastatic nodal lesions. Primary CRC showed higher expression of O-GlcNAcylation and O-GlcNAc-transferase (OGT) than nonneoplastic colons. O-GlcNAcylation expression decreased in metastatic nodal lesions compared to the invasive front and tumor center, and was inversely correlated with Ki67 LI. However, O-GlcNAcylation expression was only slightly changed between tumor center and invasive front. In addition, there was no correlation between its expression and the level of nuclear P-catenin, membranous E-cadherin and Snail. No significant relationship was observed between O-GlcNAcylation level and cliniopathological parameters. Conclusions: Differential membranous E-cadherin expression, cell proliferation and O-GlcNAcylation in metastatic nodal lesion compared to primary CRC may play role in establishing its lesions; however, these findings are not sufficient to show the role of O-GlcNAcylation in the EMT/MET of CRC (C) 2015 Elsevier GmbH. All rights reserved.