Impact of differential detection of TM6SF2 rs58542926 mutation in circulating tumor DNA versus peripheral blood cells on hepatocellular carcinoma patients

Abstract This study aimed to investigate the differential distribution of the genotypes of the TM6SF2 rs58542926 polymorphism in circulating tumor DNA (ctDNA) versus peripheral blood cells (PBMC) and its association with the development of hepatocellular carcinoma (HCC) in patients infected with the...

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Main Authors: Samar Samir Youssef, Eman Abd El Razek Abbas, Mohamed Hassany, Aya Shaaban Ragheb Shaaban, Eman Elsayed Abass Mohammed, Tamer Elbaz
Format: Article
Language:English
Published: Springer 2025-06-01
Series:Discover Oncology
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Online Access:https://doi.org/10.1007/s12672-025-02812-9
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author Samar Samir Youssef
Eman Abd El Razek Abbas
Mohamed Hassany
Aya Shaaban Ragheb Shaaban
Eman Elsayed Abass Mohammed
Tamer Elbaz
author_facet Samar Samir Youssef
Eman Abd El Razek Abbas
Mohamed Hassany
Aya Shaaban Ragheb Shaaban
Eman Elsayed Abass Mohammed
Tamer Elbaz
author_sort Samar Samir Youssef
collection DOAJ
description Abstract This study aimed to investigate the differential distribution of the genotypes of the TM6SF2 rs58542926 polymorphism in circulating tumor DNA (ctDNA) versus peripheral blood cells (PBMC) and its association with the development of hepatocellular carcinoma (HCC) in patients infected with the hepatitis C virus (HCV) in Egypt. A total of 147 HCC patients were enrolled in the study, and their genomic and ctDNA were analyzed for the TM6SF2 rs58542926 genotype. The CC genotype was identified as the most common among patients with HCC in Egypt, while the CT genotype was associated with higher serum direct bilirubin, total leucocyte count, and hemoglobin levels than those with the CC genotype. Circulating samples from patients with the CT genotype had significantly higher serum direct bilirubin, ALT, and prothrombin time than those with the CC genotype, as well as a significantly higher percentage of smokers, alcohol intake, and HCV PCR-positive patients. Our findings suggest that lifestyle factors such as smoking and alcohol intake may contribute to the development of HCC in patients with the CT genotype. Both genomic and ctDNA for the TM6SF2 rs58542926 genotype complemented and correlated with parameters of chronic liver disease and underlying risk factors for HCC. Circulating DNA for gene polymorphism provided additional real-time information and more value in correlation with the worsening of liver condition and the presence of HCC risk factors.
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spelling doaj-art-8d6a6a17997646bdabfd3e1b7138aa9c2025-08-20T03:21:06ZengSpringerDiscover Oncology2730-60112025-06-0116111310.1007/s12672-025-02812-9Impact of differential detection of TM6SF2 rs58542926 mutation in circulating tumor DNA versus peripheral blood cells on hepatocellular carcinoma patientsSamar Samir Youssef0Eman Abd El Razek Abbas1Mohamed Hassany2Aya Shaaban Ragheb Shaaban3Eman Elsayed Abass Mohammed4Tamer Elbaz5Microbial Biotechnology Department, Biotechnology Research Institute, National Research CentreMicrobial Biotechnology Department, Biotechnology Research Institute, National Research CentreTropical Medicine Department, National Hepatology and Tropical Medicine Research InstituteBiochemistry Department, Faculty of Science, Ain Shams UniversityMedical Molecular Genetics Department, Human Genetics and Genome Research Institute, National Research CentreEndemic Hepatology and Gastroenterology, Faculty of Medicine, Cairo UniversityAbstract This study aimed to investigate the differential distribution of the genotypes of the TM6SF2 rs58542926 polymorphism in circulating tumor DNA (ctDNA) versus peripheral blood cells (PBMC) and its association with the development of hepatocellular carcinoma (HCC) in patients infected with the hepatitis C virus (HCV) in Egypt. A total of 147 HCC patients were enrolled in the study, and their genomic and ctDNA were analyzed for the TM6SF2 rs58542926 genotype. The CC genotype was identified as the most common among patients with HCC in Egypt, while the CT genotype was associated with higher serum direct bilirubin, total leucocyte count, and hemoglobin levels than those with the CC genotype. Circulating samples from patients with the CT genotype had significantly higher serum direct bilirubin, ALT, and prothrombin time than those with the CC genotype, as well as a significantly higher percentage of smokers, alcohol intake, and HCV PCR-positive patients. Our findings suggest that lifestyle factors such as smoking and alcohol intake may contribute to the development of HCC in patients with the CT genotype. Both genomic and ctDNA for the TM6SF2 rs58542926 genotype complemented and correlated with parameters of chronic liver disease and underlying risk factors for HCC. Circulating DNA for gene polymorphism provided additional real-time information and more value in correlation with the worsening of liver condition and the presence of HCC risk factors.https://doi.org/10.1007/s12672-025-02812-9Hepatocellular carcinomaHCCTM6SF2 mutationHCV infection
spellingShingle Samar Samir Youssef
Eman Abd El Razek Abbas
Mohamed Hassany
Aya Shaaban Ragheb Shaaban
Eman Elsayed Abass Mohammed
Tamer Elbaz
Impact of differential detection of TM6SF2 rs58542926 mutation in circulating tumor DNA versus peripheral blood cells on hepatocellular carcinoma patients
Discover Oncology
Hepatocellular carcinoma
HCC
TM6SF2 mutation
HCV infection
title Impact of differential detection of TM6SF2 rs58542926 mutation in circulating tumor DNA versus peripheral blood cells on hepatocellular carcinoma patients
title_full Impact of differential detection of TM6SF2 rs58542926 mutation in circulating tumor DNA versus peripheral blood cells on hepatocellular carcinoma patients
title_fullStr Impact of differential detection of TM6SF2 rs58542926 mutation in circulating tumor DNA versus peripheral blood cells on hepatocellular carcinoma patients
title_full_unstemmed Impact of differential detection of TM6SF2 rs58542926 mutation in circulating tumor DNA versus peripheral blood cells on hepatocellular carcinoma patients
title_short Impact of differential detection of TM6SF2 rs58542926 mutation in circulating tumor DNA versus peripheral blood cells on hepatocellular carcinoma patients
title_sort impact of differential detection of tm6sf2 rs58542926 mutation in circulating tumor dna versus peripheral blood cells on hepatocellular carcinoma patients
topic Hepatocellular carcinoma
HCC
TM6SF2 mutation
HCV infection
url https://doi.org/10.1007/s12672-025-02812-9
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