TWIST1 hypermethylation is observed frequently in colorectal tumors and its overexpression is associated with unfavorable outcomes in patients with colorectal cancer.
Although growing evidence demonstrates that TWIST1 is an interesting tumor biomarker, little is known about the clinical significance of TWIST1 expression and TWIST1 methylation in human primary colorectal cancer. In this study, we examined the association of TWIST1 expression and TWIST1 methylation with clinicopathologic features in human primary colorectal tumors. Primary colorectal cancer (CRC) specimens from 319 patients, corresponding normal colorectal nontumorous mucosa from 251 patients with cancer, and colorectal adenomas from 189 patients were used. Methylation and expression levels of TWIST1 were compared with clinicopathologic features. The TWIST1 methylation level was higher in colorectal adenoma and cancer than in normal colorectal mucosa. Elevated TWIST1 mRNA expression in normal colorectal mucosa in patients with CRC as well as in primary CRC specimens was associated with unfavorable outcomes. There was no correlation between TWIST1 methylation and TWIST1 expression. Our results suggest that TWIST1 methylation may be a useful biomarker for screening colorectal tumors. In addition, TWIST1 mRNA expression is a possible molecular marker for predicting the outcome in patients with CRC. Confirmatory studies using independent data sets are needed to confirm our findings.
Department of Oncology and Laboratory Medicine, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan.
Toshiyuki
T
Okada
Yutaka
Y
Suehiro
Koji
K
Ueno
Shoko
S
Mitomori
Sayaka
S
Kaneko
Mitsuaki
M
Nishioka
Naoko
N
Okayama
Kouhei
K
Sakai
Shingo
S
Higaki
Shoichi
S
Hazama
Hiroshi
H
Hirata
Isao
I
Sakaida
Masaaki
M
Oka
Yuji
Y
Hinoda
D000236:Adenoma / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D002874:Chromosome Mapping; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation / Q000187:drug effects / Q000235:genetics*; D000077209:Decitabine; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000378:metabolism; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011379:Prognosis; D017422:Sequence Analysis, DNA; D018709:Statistics, Nonparametric; D051879:Twist-Related Protein 1 / Q000096:biosynthesis / Q000235:genetics*
D006877:Hydroxamic Acids; D009687:Nuclear Proteins; C103173:TWIST1 protein, human; D051879:Twist-Related Protein 1; C012589:trichostatin A; D000077209:Decitabine; D001374:Azacitidine