title: 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.
authors.affiliation: Department of Medicine, The Graduate School, CHA University, Bundang-gu, Seongnam 463-712, Republic of Korea.
authors.forename: Yong Hun
authors.initials: YH
authors.lastname: Kim
authors.affiliation: Department of Pathology, Bundang CHA Medical Center, CHA University, Bundang-gu, Seongnam 463-712, Republic of Korea.
authors.forename: Gwangil
authors.initials: G
authors.lastname: Kim
authors.affiliation: Digestive Disease Center, Bundang CHA Medical Center, CHA University, Bundang-gu, Seongnam 463-712, Republic of Korea.
authors.forename: Chang-Il
authors.initials: CI
authors.lastname: Kwon
authors.affiliation: Digestive Disease Center, Bundang CHA Medical Center, CHA University, Bundang-gu, Seongnam 463-712, Republic of Korea.
authors.forename: Jong Woo
authors.initials: JW
authors.lastname: Kim
authors.affiliation: Digestive Disease Center, Bundang CHA Medical Center, CHA University, Bundang-gu, Seongnam 463-712, Republic of Korea.
authors.forename: Pil Won
authors.initials: PW
authors.lastname: Park
authors.affiliation: Digestive Disease Center, Bundang CHA Medical Center, CHA University, Bundang-gu, Seongnam 463-712, Republic of Korea.
authors.forename: Ki-Baik
authors.initials: KB
authors.lastname: Hahm
mesh_terms: D002288:Adenocarcinoma, Mucinous / Q000378:metabolism* / Q000401:mortality / Q000556:secondary; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000080924:Aldehyde Dehydrogenase 1 Family; D015703:Antigens, CD; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D015870:Gene Expression; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D014411:Neoplastic Stem Cells / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D050697:Retinal Dehydrogenase / Q000378:metabolism*; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D051879:Twist-Related Protein 1 / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D014408:Biomarkers, Tumor; C513384:CDH1 protein, human; C495270:CTNNB1 protein, human; D015820:Cadherins; D007527:Isoenzymes; D009687:Nuclear Proteins; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; C508960:TGFB1 protein, human; C103173:TWIST1 protein, human; D014157:Transcription Factors; D053773:Transforming Growth Factor beta1; D051879:Twist-Related Protein 1; D051176:beta Catenin; D000080924:Aldehyde Dehydrogenase 1 Family; C510223:ALDH1A1 protein, human; D050697:Retinal Dehydrogenase