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Single Nucleotide Polymorphisms of Toll-like Receptor 4 in Hepatocellular Carcinoma—A Single-Center Study

Hepatocellular carcinoma (HCC) is the most common primary liver tumor leading to significant morbidity and mortality; its exact genetic background is largely unrecognized. Toll-like receptor-4 (TLR4) reacts with lipopolysaccharides, molecules found in the outer membrane of Gram-negative bacteria. In...

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Autores principales: Androutsakos, Theodoros, Bakasis, Athanasios-Dimitrios, Pouliakis, Abraham, Gazouli, Maria, Vallilas, Christos, Hatzis, Gregorios
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9409058/
https://www.ncbi.nlm.nih.gov/pubmed/36012696
http://dx.doi.org/10.3390/ijms23169430
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author Androutsakos, Theodoros
Bakasis, Athanasios-Dimitrios
Pouliakis, Abraham
Gazouli, Maria
Vallilas, Christos
Hatzis, Gregorios
author_facet Androutsakos, Theodoros
Bakasis, Athanasios-Dimitrios
Pouliakis, Abraham
Gazouli, Maria
Vallilas, Christos
Hatzis, Gregorios
author_sort Androutsakos, Theodoros
collection PubMed
description Hepatocellular carcinoma (HCC) is the most common primary liver tumor leading to significant morbidity and mortality; its exact genetic background is largely unrecognized. Toll-like receptor-4 (TLR4) reacts with lipopolysaccharides, molecules found in the outer membrane of Gram-negative bacteria. In damaged liver, TLR4 expression is upregulated, leading to hepatic inflammation and injury. We tried to investigate the role of the two most common single-nucleotide polymorphisms (SNPs) of TLR4 in HCC-genesis. Aged > 18 years old, cirrhotic patients were included in this study. Exclusion criteria were non-HCC tumors and HIV co-infection. TLR4 SNPs association with HCC occurrence was the primary endpoint, and associations with all-cause and liver-related mortality, as well as time durations between diagnosis of cirrhosis and HCC development or death and diagnosis of HCC and death were secondary endpoints. A total of 52 out of 260 included patients had or developed HCC. TLR4 SNPs showed no correlation with primary or secondary endpoints, except for the shorter duration between HCC development and death in patients with TLR4 mutations. Overall, TLR4 SNPs showed no correlation with carcinogenesis or deaths in patients with liver cirrhosis; patients with TLR4 SNPs that developed HCC had lower survival rates, a finding that should be further evaluated.
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spelling pubmed-94090582022-08-26 Single Nucleotide Polymorphisms of Toll-like Receptor 4 in Hepatocellular Carcinoma—A Single-Center Study Androutsakos, Theodoros Bakasis, Athanasios-Dimitrios Pouliakis, Abraham Gazouli, Maria Vallilas, Christos Hatzis, Gregorios Int J Mol Sci Article Hepatocellular carcinoma (HCC) is the most common primary liver tumor leading to significant morbidity and mortality; its exact genetic background is largely unrecognized. Toll-like receptor-4 (TLR4) reacts with lipopolysaccharides, molecules found in the outer membrane of Gram-negative bacteria. In damaged liver, TLR4 expression is upregulated, leading to hepatic inflammation and injury. We tried to investigate the role of the two most common single-nucleotide polymorphisms (SNPs) of TLR4 in HCC-genesis. Aged > 18 years old, cirrhotic patients were included in this study. Exclusion criteria were non-HCC tumors and HIV co-infection. TLR4 SNPs association with HCC occurrence was the primary endpoint, and associations with all-cause and liver-related mortality, as well as time durations between diagnosis of cirrhosis and HCC development or death and diagnosis of HCC and death were secondary endpoints. A total of 52 out of 260 included patients had or developed HCC. TLR4 SNPs showed no correlation with primary or secondary endpoints, except for the shorter duration between HCC development and death in patients with TLR4 mutations. Overall, TLR4 SNPs showed no correlation with carcinogenesis or deaths in patients with liver cirrhosis; patients with TLR4 SNPs that developed HCC had lower survival rates, a finding that should be further evaluated. MDPI 2022-08-21 /pmc/articles/PMC9409058/ /pubmed/36012696 http://dx.doi.org/10.3390/ijms23169430 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Androutsakos, Theodoros
Bakasis, Athanasios-Dimitrios
Pouliakis, Abraham
Gazouli, Maria
Vallilas, Christos
Hatzis, Gregorios
Single Nucleotide Polymorphisms of Toll-like Receptor 4 in Hepatocellular Carcinoma—A Single-Center Study
title Single Nucleotide Polymorphisms of Toll-like Receptor 4 in Hepatocellular Carcinoma—A Single-Center Study
title_full Single Nucleotide Polymorphisms of Toll-like Receptor 4 in Hepatocellular Carcinoma—A Single-Center Study
title_fullStr Single Nucleotide Polymorphisms of Toll-like Receptor 4 in Hepatocellular Carcinoma—A Single-Center Study
title_full_unstemmed Single Nucleotide Polymorphisms of Toll-like Receptor 4 in Hepatocellular Carcinoma—A Single-Center Study
title_short Single Nucleotide Polymorphisms of Toll-like Receptor 4 in Hepatocellular Carcinoma—A Single-Center Study
title_sort single nucleotide polymorphisms of toll-like receptor 4 in hepatocellular carcinoma—a single-center study
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9409058/
https://www.ncbi.nlm.nih.gov/pubmed/36012696
http://dx.doi.org/10.3390/ijms23169430
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