GFBR3 Promoter Methylation Is A Prognostic Indicator And Not Responding To Decitabine Treatment In Hepatocellular Carcinoma

Document Type : Original Article

Authors

1 misr university for science and technology

2 Technology of Medical Laboratory Department, College of Applied Health Science Technology, Misr University for Science and Technology, 6th October, Egypt.

3 Biochemistry Department, Faculty of Science, Beni-Suef University

4 Faculty of pharmacy, Beni suef university, Egypt

5 Student Hospital Cairo university

6 Department of Cancer Biology, National Cancer Institute, Cairo University, Cairo, Egypt.

Abstract

Previous studies have demonstrated lower levels of TGFBR3 in cancer cells compared to non-cancerous cells. And the low levels are related to the clinical characteristics of the patients. However, there is no study examined the relationship between the degree of methylation of TGFBR3 and patient data in liver cancer. The aim of this study is to test the role of decitabine in demethylating TGFBR3 and the expression of miRNAs in HepG2 cells and to study the relationship between TGFBR3 methylation level and clinical data and follow-up in HCC. Five and 10 micromoles of decitabine and 0.6 micromoles of doxorubicin were used on HepG2 cells, and the degree of methylation of TGFBR3 and the expression of a group of miRNAs were assessed. The degree of methylation was studied in 14 liver cancer tissue samples and 4 adjacent non tumor tissue samples. TGFBR3 methylation levels were correlated to clinical data and patient’s follow-up. TGFBR3 methylation did not change after treatment with decitabine. Decitabine upregulated MiR-10b-5p, miR-125b-5p, miR-196-5p, miR-596 in a concentration dependent manner. TGFBR3 methylation level was significantly higher in HCC than NTD (0.000456). TGFBR3 methylation level was significantly correlated to gender (0.047), grade (0.00001), LN metastasis (0.005), safety margin (0.001), AFP level (0.0003), albumin level (0.00001), platelets count (0.0005), DFS (0.00001) and OS (0.00001). Conclusion: Decitabine failed to demethylate TGFBR3 in HCC. Decitabine randomly influenced the expression of oncogenic and tumor suppressive miRNAs. TGFBR3 methylation is promising in predicting LN metastasis and survival in HCC patients.

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Egyptian Journal of Chemistry
Volume 66, Issue 13 - Serial Number 13
Special Issue: Applied Chemistry for Greener Life and Sustainability
December 2023
Pages 807-817

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History

  • Receive Date: 31 January 2023
  • Revise Date: 31 October 2023
  • Accept Date: 26 April 2023

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