RRC ID 43563
Author Lee KW, Kim JH, Han S, Sung CO, Do IG, Ko YH, Um SH, Kim SH.
Title Twist1 is an independent prognostic factor of esophageal squamous cell carcinoma and associated with its epithelial-mesenchymal transition.
Journal Ann. Surg. Oncol.
Abstract BACKGROUND:Twist1 is known to be involved in epithelial-mesenchymal transition (EMT) and tumor progression. However, its specific role is different depending on the type of cancer. The functional role and clinical significance of Twist1 in esophageal squamous cell carcinoma (ESCC) have been rarely studied.
METHODS:We examined Twist1 expression in a total of 199 samples using immunohistochemistry and real-time reverse-transcription polymerase chain reaction (RT-PCR). We also studied the association of Twist1 with EMT of ESCC using tissue samples and in vitro models. In addition, we examined the changes in the whole-genome expression profiles of two ESCC cell lines after inducing upregulation of Twist1.
RESULTS:Twist1 expression was increased in ESCC compared with that of normal esophagus (P < 0.01). We found that expression of Twist1 was strongly associated with poor prognosis on both univariate analysis [relative risk (RR) = 3.019, P = 0.000] and multivariate analysis (RR = 3.131, P = 0.000). In addition, we found that Twist1 expression was strongly correlated with EMT in ESCC tissues. Upregulation of Twist1 induced other EMT inducers in all three esophageal cancer cell lines investigated (TE1, TE8, and TE10). Twist1 also enhanced the migratory and invasive abilities of all three cell lines. Finally, microarray analysis of gene expression in the three ESCC cell lines revealed that Twist1 upregulation affected the expression of mainly cytoskeleton and extracellular matrix-related genes, which are directly related to cell morphology and movement.
CONCLUSIONS:Our study indicates that Twist1 is associated with EMT of esophageal squamous cell carcinoma and may be used as a diagnostic and prognostic biomarker in ESCC.
Volume 19(1)
Pages 326-35
Published 2012-1
DOI 10.1245/s10434-011-1867-0
PMID 21732143
MeSH Biomarkers, Tumor / genetics Biomarkers, Tumor / metabolism Carcinoma, Squamous Cell / genetics* Carcinoma, Squamous Cell / metabolism Carcinoma, Squamous Cell / mortality Carcinoma, Squamous Cell / pathology* Case-Control Studies Epithelial-Mesenchymal Transition* Esophageal Neoplasms / genetics* Esophageal Neoplasms / metabolism Esophageal Neoplasms / mortality Esophageal Neoplasms / pathology* Esophagus / metabolism Esophagus / pathology Female Follow-Up Studies Gene Expression Profiling Humans Immunoenzyme Techniques Lymphatic Metastasis Male Middle Aged Neoplasm Staging Nuclear Proteins / genetics* Nuclear Proteins / metabolism Oligonucleotide Array Sequence Analysis Prognosis RNA, Messenger / genetics RNA, Messenger / metabolism Reverse Transcriptase Polymerase Chain Reaction Survival Rate Tumor Cells, Cultured Twist-Related Protein 1 / genetics* Twist-Related Protein 1 / metabolism
IF 3.681
Times Cited 29
Human and Animal Cells