TWIST1 and SNAI1 as markers of poor prognosis in human colorectal cancer are associated with the expression of ALDH1 and TGF-β1

Abstract

Epithelial-mesenchymal transition (EMT) is an important factor in cancer invasiveness and metastatic progression. During EMT, cancer cells acquire stem cell properties. The role of EMT and stemness in colon cancer has not been fully understood. We aimed to demonstrate the clinical significance of EMT and the stem cell phenotype in colorectal cancer. Two hundred and thirty-one surgically resected colon cancer cases were included in the present study. mRNAs of E-cadherin, TWIST1 and SNAI1 were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) (n=109). Immunohistochemical staining was performed for six markers (ALDH1, TGF-β1, E-cadherin, β-catenin, TWSIT1 and SNAI1) (n=231). We assessed clinicopathological characteristics according to the expression of the stem cell phenotype and EMT markers. Based on the results of qRT-PCR, TWIST1 and SNAI1 significantly influenced node metastasis (P=0.04 and P=0.02, respectively). High TWIST1 and SNAI1 mRNA expression was associated with poor overall survival according to the univariate analysis (P<0.01 and P=0.01, respectively) and the multivariate analysis (P=0.04 and P=0.04, respectively). ALDH1 expression as detected by immunohistochemical staining was associated with high nodal stage, advanced clinical stage, lymphatic invasion and poor survival (P=0.01, P=0.04, P<0.05 and P<0.01, respectively) and with the expression of TGF-β1 and β-catenin. In conclusion, in human colorectal cancer, the EMT markers TWIST1 and SNAI1 are suggested as important markers of poor prognosis. Their expression is associated with the expression of putative stem cell marker ALDH1, and ALDH1 is associated with the expression of TGF-β1.