Abstract
Epigenetic changes in CpG islands of the promoter regions of homeostasis-related genes, including nuclear factor erythroid 2-related factor 2 (NRF2), have been shown to hold a significant role in the development of colorectal cancer. Therefore, we aimed to examine the DNA demethylation pattern of the NRF2 promoter region in cancerous lesions from patients with colorectal cancer and the association of methylation status with clinicopathological features in the Iranian population. In this cross-sectional study, 114 colorectal tissue samples were collected. These samples included: 34 tumour tissue samples, 60 precancerous polyps, and 20 normal tissue samples. The promoter methylation status of the NRF2 gene was examined using methylation-specific PCR. Additionally, the relationship between the methylation status and the clinicopathological features was investigated. The frequency of NRF2 demethylation in the tumour samples was significantly higher compared to the polyp tissues (p= 0.003) and normal tissue (p= 0.009), indicating that cancerous colorectal tissues exhibit increased demethylation of the NRF2 promoter. After examining the demethylation status of tissue samples, the clinicopathological features were compared to the demethylation results. No significant association was found between NRF2 promoter demethylation and the clinicopathological features of patient samples. Our findings suggest that the epigenetic modifications leading to NRF2 demethylation found in colorectal tumour samples may contribute to cancer progression from precancerous polyps to cancerous lesions.
Highlights
Colorectal cancer (CRC) is one of the most commonly diagnosed malignant neoplasms, making it a major public health problem worldwide
Epigenetic analysis of nuclear factor erythroid 2-related factor 2 (NRF2) in the different types of colorectal specimens The results reported in Table 4 reveal that the NRF2 promoter was demethylated in most of the tumour samples (61.8%)
Our findings indicate that the methylation status of NRF2 was significantly dependent on type of the colorectal tissue sample examined (p= 0.004)
Summary
Colorectal cancer (CRC) is one of the most commonly diagnosed malignant neoplasms, making it a major public health problem worldwide. Tumorigenesis begins as a polyp growing in the inner surface of the colon or rectum [1] These colorectal polyps are believed to be the main source of precancerous cells leading to the development of CRC [2]. We aimed to examine the DNA demethylation pattern of the NRF2 promoter region in cancerous lesions from patients with colorectal cancer and the association of methylation status with clinicopathological features in the Iranian population. Methods: In this cross-sectional study, 114 colorectal tissue samples were collected These samples included: 34 tumour tissue samples, 60 precancerous polyps, and 20 normal tissue samples. Conclusions: Our findings suggest that the epigenetic modifications leading to NRF2 demethylation found in colorectal tumour samples may contribute to cancer progression from precancerous polyps to cancerous lesions
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