TWIST1 hypermethylation is observed frequently in colorectal tumors and its overexpression is associated with unfavorable outcomes in patients with colorectal cancer

Abstract

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.

Methylated genes in breast cancer

“…For example, only two studies have examined the relationship between TWIST promoter hypermethylation and TWIST RNA and protein, and did not find any alteration in gene expression. 24,25 Although the limited archival tumor tissues in our sample set did not allow gene expression to be assayed in tandem with methylation, with the exception of TWIST, methylation has consistently been associated with transcriptional silencing of the remaining gene loci covered by our primers.…”

TWIST1 hypermethylation is observed in pancreatic cancer

“…However, upregulation of TWIST mRNA in pancreatic cancer has been reported (12). This discrepancy may be due to the lack of a direct correlation between TWIST1 methylation and TWIST1 expression in primary colorectal (9) and breast cancers (13). Characteristics other than TWIST1 methylation may also affect TWIST1 expression in pancreatic cancer.…”

“…Bisulfite treatment was performed as reported previously (9). Two micrograms of genomic DNA in 50 µl of water were denatured with 5.5 µl of 2 M NaOH at 37˚C for 10 min, followed by incubation with 30 µl of 10 mM hydroquinone and 520 µl of 3 M sodium bisulfite (pH 5.0) at 50˚C for 16 h in the dark.…”

“…Formalin-fixed, paraffin-embedded primary pancreatic cancer tissues and corresponding non-neoplastic pancreatic tissues from 33 patients who underwent surgical resection between 2004 and 2009 were evaluated. DNA was prepared from cells in microdissected, 5-µm histopathological sections, as described previously (9). Clinicopathological characteristics were available for the patients.…”

“…TWIST1 is a highly conserved transcription characteristic that belongs to the family of basic helixloop-helix proteins and is involved in embryonic development through the regulation of the migration-invasion program [termed the epithelial-mesenchymal transition (EMT)] during neural crest migration, while regulating mesodermal determination, myogenesis and morphogenesis (3)(4)(5). Although growing evidence demonstrates that TWIST1 methylation is a notable tumor biomarker in various tumors (6)(7)(8)(9), little is known concerning the clinical significance of TWIST1 methylation in human primary pancreatic cancer. These correlations were investigated in the present study.…”