TWIST1 Promoter Methylation in Primary Colorectal Carcinoma

Abstract

TWIST1 gene, a transcription factor that belongs to the family of basic helix-loop-helix proteins, has been related to tumor progression and metastasis in different cancers. The aim of our study was to investigate TWIST1 promoter methylation in patients with primary colorectal carcinoma and determine its correlation with prognostic factors and disease outcome. Seventy-three patients with primary colorectal adenocarcinoma were studied. From each patient two tissue samples were collected: one sample of the tumor and one sample of normal colorectal tissue from an area located 15 cm away from the tumor. Samples of colorectal mucosa obtained from 30 individuals without malignant disease were also studied as a control group. All tissues were analyzed through methylation-specific PCR. TWIST1 hypermethylation was detected in colorectal specimens of 46 patients with cancer, but in none of the tissues from the nonmalignant control group (p < 0.001). In cancer patients, TWIST1 hypermethylation was found in 38 of 73 tumor samples as compared with 20 of 73 matched samples of non-cancerous colorectal tissue (P = 0.001). TWIST1 hypermethylation was not correlated with prognostic predictors for the disease outcome, patients' overall survival and disease-free survival rates. We concluded that TWIST1 hypermethylation is present in the colon and rectum of most patients with colorectal carcinoma, suggesting this molecular alteration may be involved in the process of colorectal carcinogenesis.

TWIST1 and TWIST2 promoter methylation and protein expression in tumor stroma influence the epithelial-mesenchymal transition-like tumor budding phenotype in colorectal cancer

“…Moreover, Ashktorab and colleagues, performing an extensive bioinformatics work on CpG island Methylator Phenotype, identified TWIST1 as markedly hypermethylated in colorectal cancer [31]. Other groups report methylation percentages of >40% across these tumors [32, 33]. Our results confirm these findings not only for TWIST1 but also TWIST2.…”

“…We observed lack of correlation between hypermethylation and protein expression in normal colorectal mucosa may suggest that hypermethylation as a regulatory mechanism of TWIST1 and TWIST2 may be restricted to the tumor microenvironment. These results are supported by others [25, 33]. Other mechanisms of TWIST1 regulation in normal tissue may include post-translational histone modifications, however this aspect still remains to be elucidated.…”

Toward a comprehensive and systematic methylome signature in colorectal cancers

“…Of these, 118 targets samples. [20][21][22] Deleted in colon cancer (DCC) methylation is a frequent event in CRC, and three independent studies have found high rates (82%, 80%, and 56%) of DCC promoter methylation in primary and sporadic CRC using MSP, COBRA, and qMSP approaches, respectively. [23][24][25][26][27][28] Genome-wide analysis have cited Receptor Protein Tyrosine Phosphatase Delta gene (PTPRD) as hypermethylated in CRC and a predictor of poor prognosis, 12 an observation that was previously corroborated by our laboratory in Iranian and African American populations.…”

Aminopeptidase A initiates tumorigenesis and enhances tumor cell stemness via TWIST1 upregulation in colorectal cancer

“…TWIST, which is frequently overexpressed or hypermethylated, has important implications for tumor metastasis in colon cancer [31, 32]. It is therefore important to understand the role of upstream TWIST regulation in production and regulation pathways, and how it might provide benefits in terms of early cancer treatment [33].…”