title: Snail promotes lymph node metastasis and Twist enhances tumor deposit formation through epithelial-mesenchymal transition in colorectal cancer.
abstract: Snail and Twist, transcriptional repressors of E-cadherin as well as inducers of epithelial-mesenchymal transition, play pivotal roles in tumor invasion and metastasis. We investigated the expression of Snail, Twist, and E-cadherin by immunohistochemistry in 193 colorectal cancers, including 79 with positive lymph nodes, 36 with tumor deposits, 39 with both, and 39 with no metastases. Snail was expressed to a greater extent in the group with positive lymph nodes (68.4%), whereas Twist was overexpressed in patients with other metastases (75.0%). Ectopic expression of Snail and Twist correlated with reduced membranous expression of E-cadherin. Importantly, Snail overexpression correlated significantly with lymph node metastasis (P < .0001), whereas Twist up-regulation correlated strongly with other metastases (P < .0001). Multivariate logistic regression analysis showed that Snail was an independent predictor of lymph node metastasis (odds ratio, 4.445; 95% confidence interval, 2.250-8.781; P < .0001), whereas Twist displayed predictive value for metastasis formation (odds ratio, 5.606; 95% confidence interval, 2.829-11.111; P < .0001), suggesting that lymph node and other metastases may follow different signaling pathways. In conclusion, ectopic expression of Snail and Twist contributed to lymph node and disseminated metastasis, respectively, by reducing E-cadherin expression, providing a novel role for Snail and Twist in the progression of colorectal cancer.
authors.affiliation: Department of Pathology, Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, China.
authors.forename: Xin-Juan
authors.initials: XJ
authors.lastname: Fan
authors.forename: Xiang-Bo
authors.initials: XB
authors.lastname: Wan
authors.forename: Zu-Li
authors.initials: ZL
authors.lastname: Yang
authors.forename: Xin-Hui
authors.initials: XH
authors.lastname: Fu
authors.forename: Yan
authors.initials: Y
authors.lastname: Huang
authors.forename: Dian-Ke
authors.initials: DK
authors.lastname: Chen
authors.forename: Shun-Xin
authors.initials: SX
authors.lastname: Song
authors.forename: Quentin
authors.initials: Q
authors.lastname: Liu
authors.forename: Huan-Yu
authors.initials: HY
authors.lastname: Xiao
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Wang
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology*; D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008198:Lymph Nodes / Q000378:metabolism; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D000071250:Snail Family Transcription Factors; D046888:Tissue Array Analysis; D014157:Transcription Factors / Q000378:metabolism*; D051879:Twist-Related Protein 1 / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D015820:Cadherins; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D051879:Twist-Related Protein 1