The correlation of epithelial-mesenchymal transition-related gene expression and the clinicopathologic features of colorectal cancer patients in Taiwan

Abstract

Colorectal cancer (CRC) is the third most commonly diagnosed malignancy and the second leading cause of cancer-related deaths in the world. It has been the most prevalent malignancy in Taiwan for consecutive thirteen years. Despite the diversity of its etiologic and pathophysiologic factors, a biological process named as epithelial-mesenchymal transition (EMT) is indispensable in the progression of epithelial cancer. Our aim is to investigate the correlation between the expression of 8 EMT-related proteins (E-cadherin, β-catenin, claudin-1, CD44, N-cadherin, fibronectin, vimentin, S100A4) and the clinicopathologic features of CRC in Taiwan, along with the DNA CpG epigenetic status of CD44 gene. In immunohistochemical assessment, decreased expression of E-cadherin is statistically associated with the progression of cancer stage, while decreased expression of claudin-1 as well as increased β-catenin nuclear translocation and N-cadherin expression is statistically associated with the progression of histopathologic grade. E-cadherin, nuclear β-catenin and claudin-1 are also associated with other important prognostic factors, including nodal metastasis, tumor deposits, and elevated serum CA 19–9 levels. In addition, the left-sided colon and rectal cancers show increased nuclear translocation of β-catenin compared to the right-sided colon cancers, while the rectal cancers show increased fibronectin expression compared to the right-sided and left-sided colon cancers. Moreover, vimentin is aberrantly expressed in one case of signet-ring cell carcinoma. The DNA methylation levels of CD44 gene promoter between the tumoral and non-tumorous tissues by NGS comparison showed statistical difference on six CpG sites. However, such difference may not be sufficient because these DNA methylation proportions are too low to inactivate CD44 gene. Our results demonstrate the expression of E-cadherin, claudin-1, and nuclear β-catenin is closely related to the clinicopathologic prognostic determinants of CRC in Taiwan. The DNA methylation level of CD44 gene and its protein expression, however, show no correlation with the clinicopathologic features in CRC.

The Expression of the Claudin Family of Proteins in Colorectal Cancer

“…Using IHC, seventeen groups reported that 54–100% of CRCs exhibited CLDN1 staining ( Table 2 ) [ 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 37 , 46 , 56 , 57 , 58 , 59 , 60 , 61 , 62 ]. Multiple groups also directly compared the staining patterns of CRC to the normal colon with two groups reporting that overall, staining patterns were stronger in CRC ( Figure 1 ) [ 63 ].…”

“…Based on the currently available body of work on the protein expression of claudins in colorectal cancer, CLDN1, CLDN2, CLDN4, and CLDN18 have all been reported to be expressed in CRC [ 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 37 , 46 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 73 , 74 , 75 , 80 , 81 , 93 , 96 , 152 , 153 , 160 , 161 , 162 , 163 , 164 ]. Although CLDN6 and CLDN7 are expressed in CRC, their levels are reduced compared to the normal colon [ 44 , 62 , 105 , 106 , 119 , 122 , 124 , 125 ].…”