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. 2024 Sep;22(3):100394.
doi: 10.1016/j.jgeb.2024.100394. Epub 2024 Jun 5.

Measuring the differential expression of the major hypermethylated tumor suppressor genes in tissues of primary hepatocellular carcinoma

Khalda Sayed Amr  1 , Wafaa Mohamed Ezzat  2 , Ahmed Ibrahim Saleh  3 , Ahmed Heiba  2 , Hend Amin  2 , Refaat Refaat Kamel  4 , Noha Eltaweel  1 , Hoda Henery  5 , Amr Omaia  2 , Reham Ibrahim Siddik  2 , Yasser Abdelghany Abdelazeem Elhosary  2
Affiliations

Measuring the differential expression of the major hypermethylated tumor suppressor genes in tissues of primary hepatocellular carcinoma

Khalda Sayed Amr et al. J Genet Eng Biotechnol. 2024 Sep.

Abstract

Background: Hepatocarcinogenesis is a multifactorial process that arises from a integration of genetic and epigenetic anomalies leading to abnormal gene expression and function. It is difficult to characterize HCC with a single biomarker. Our study aimed at detecting the expression of a panel of 8 methylated genes (SOCS1, APC, Gadd45b, CDKN1B, P15, PAX6, STAT1 and MSH2) as regulatory factors among Egyptian patients with HCC.

Methods: This study was conducted on HCC tissue samples of 30 Egyptian patients in comparison with their non-cancerous adjacent cirrhotic tissue as a control. Tissue samples were obtained from patients who have undergone living donor liver transplantation (LDLT) or liver resection at El Sahel Teaching Hospital (Cairo, Egypt). A special Custom designed PCR Arrays was used to analyze the expression profiles of chosen methylated genes associated with HCC.

Results: Expression of SOCS1, APC, Gadd45b, CDKN1B, P15, PAX6, STAT1 and MSH2 were lower in the HCC tissue compared to the cirrhotic tissue (pvalue = 0.015, 0.081, 0.004, 0.027, 0.211, 0.015, 0.025 and 0.0001 respectively). 5 genes (SOCS1, APC, GAdd45b, CDKN1B, and MSH2) showed the ability to be used as diagnostic biomarkers for HCC with high sensitivity and specificity values at cut off values: 1.05, 1.17, 0.995, 0.546, and 0.125 respectively. As for the other 3 genes (P15, PAX6, STAT1), PAX6 gene has the highest sensitivity at a cut off value of 0.3364. A significant negative correlation was shown between alpha fetoprotein (AFP) and 5 of the studied genes (SOCS1, APC, Gadd45b, STAT1, and MSH2).

Conclusions: Expression of the selected hypermethylated genes (SOCS1, APC, Gadd45b, CDKN1B, P15, PAX6, STAT1 and MSH2) in HCC tissue samples was lower than adjacent tissue. Their role should be further studied to solve the mystery that surrounds the pathogenesis of HCC.

Keywords: Gene hyper methylation; Hepatocellular carcinoma.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
ROC curve for S0CS1, APC, Gadd45b and CDKN1B genes.
Fig. 2
Fig. 2
ROC curve for P15, PAX6, STAT1 and MSH2 genes.
Fig. 3
Fig. 3
Clustergram of the studied genes vs enriched terms by disgenet. enriched terms are the columns, input genes are the rows, and cells in the matrix indicate if a gene is associated with a term.
See this image and copyright information in PMC

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