The DNA Methylation is Involved in Liver Cancer Metastasis via Regulation of E- cadherin Gene

Abstract

Over 90% of primary liver tumors are hepatocellular carcinomas (HCCs). In mammalian cells, chromatin remodeling and transcription regulation are significantly influenced by DNA methylation. Many cancers demonstrate both generalized DNA hypomethylation and localized DNA hypermethylation. Epithelial Cadherin (E-cadherin), a critical molecule in cell adhesion and cancer progression, is involved in these processes. This study aimed to investigate the biological role of DNA methyltransferase 1 (DNMT1) in HCC and its association with E-cadherin gene expression in HCC development. The study included 120 HCC patients from Egypt and 25 healthy individuals. Peripheral blood samples were collected from both groups, and quantitative real-time PCR was utilized to measure the expression levels of the E-cadherin and DNMT1 genes. All participants underwent a comprehensive medical history review and clinical examination. Additionally, the patients had laboratory tests, including serum alanine aminotransferase (ALT), serum aspartate aminotransferase (AST), α-fetoprotein (AFP), albumin, serum creatinine, total leukocyte count (TLC), and platelet count. The results revealed significantly higher levels of these biochemical markers in the HCC group compared to the control group (P values < 0.005). Notably, DNMT1 expression was significantly higher in HCC samples compared to those from healthy controls. In contrast, the expression of E-cadherin was significantly reduced in the HCC group. Furthermore, our findings revealed that the relative gene expression of DNMT1 was negatively correlated with the relative gene expression of E-cadherin, AFP, and tumor size, while E-cadherin expression was negatively correlated with AFP and tumor size. These results suggest that DNMT1 may play a vital role in regulating E-cadherin expression, which could influence the migratory behavior of HCC cells.

Keywords: DNA methyltransferase 1; Epithelial Cadherin; Hepatocellular carcinoma.

Figure 1

The Expression of the DNMT1 Gene was Compared to Blood Samples Obtained from Healthy Individuals Elevated in HCCs Compared to Normal Liver Cells, showing a fold change of 11.4. Additionally, the presence of the DNMT1 gene in HCCs was significantly associated with poor tumor differentiation (*** indicating that P ≤ 0.005).

Figure 2

The Expression of the E-Cadherin Gene was Downregulated in Hepatocellular Carcinomas (HCCs) Compared to Normal Liver Cells, with in HCC a Fold Change of 0.55. compared to samples derived from healthy control, the presence of E-Cadherin gene expression in HCCs was significantly associated with poorer tumor differentiation (***) with a P-value ≤ 0.005.

Figure 3

The Relative Gene Expression of E-cadherin and DNMT1 in HCC Patients with Different Clinical Manifestations. (A) Significant statistical correlation between E-cadherin expression and tumor grades; (B) Significant statistical correlation between DNMT1 expression and tumor grades (P<0.005).

Figure 4.

The Correlation between E. Cadherin and DNMT1 (r= -0.2538) P<0.0001.

Figure 5

. (A) The positive correlation (r=0.279) between DNMT1 and AFP P<0.0001. (B) Negative correlation (r= - 0.0883) between E. Cadherin and AFP P<0.0001, (C) Positive correlation (r =0.0755) between DNMT1 and tumor size P<0.0001, and (D) Negative correlation (r = - 0.0953) between E. Cadherin and tumor size P<0.0001