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Screening of co-pathogenic genes of non-alcoholic fatty liver disease and hepatocellular carcinoma

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a risk factor for hepatocellular carcinoma (HCC). However, its carcinogenic mechanism is still unclear, looking for both diseases’ transcriptome levels, the same changes as we are looking for NAFLD may provide a potential mechanism of action o...

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Autores principales: Chen, Ting, Zhang, Siwen, Zhou, Dongmei, Lu, Peipei, Mo, Xianglai, Tamrakar, Rashi, Yang, Xi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9410624/
https://www.ncbi.nlm.nih.gov/pubmed/36033523
http://dx.doi.org/10.3389/fonc.2022.911808
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author Chen, Ting
Zhang, Siwen
Zhou, Dongmei
Lu, Peipei
Mo, Xianglai
Tamrakar, Rashi
Yang, Xi
author_facet Chen, Ting
Zhang, Siwen
Zhou, Dongmei
Lu, Peipei
Mo, Xianglai
Tamrakar, Rashi
Yang, Xi
author_sort Chen, Ting
collection PubMed
description BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a risk factor for hepatocellular carcinoma (HCC). However, its carcinogenic mechanism is still unclear, looking for both diseases’ transcriptome levels, the same changes as we are looking for NAFLD may provide a potential mechanism of action of HCC. Thus, our study aimed to discover the coexisting pathogenic genes of NAFLD and HCC. METHODS: We performed a variance analysis with public data for both diseases. At the same time, weighted gene correlation network analysis (WGCNA) was used to find highly correlated gene modules in both diseases. The darkturquoise gene module was found to be highly correlated with both diseases. Based on the diagnosis related module genes and the differential genes of the two diseases, we constructed diagnostic and prognostic models by logistic regression, univariate Cox regression, and LASSO regression. Public datasets verified the results. Meanwhile, we built a competing endogenous RNA (ceRNA) network based on the model genes and explored the related pathways and immune correlation involved in the two diseases by using Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and gene set enrichment analyses. Immunohistochemistry was used to verify the different expression of ABCC5 and TUBG1 among the normal liver, NAFLD, and HCC tissues. Sodium palmitate/sodium oleate was used to establish high-fat cell models, and Real Time Quantitative Polymerase Chain Reaction (RT-qPCR) was used to verify the messenger RNA (mRNA) expression of ABCC5 in lipidization cells. RESULTS: A total of 26 upregulated genes and 87 downregulated genes were found using limma package identification analysis. According to WGCNA, the darkturquoise gene module was highly correlated with the prognosis of both diseases. The coexisting genes acquired by the two groups were only three central genes, that is, ABCC5, DHODH and TUBG1. The results indicated that the diagnostic and prognostic models constructed by ABCC5 and TUBG1 genes had high accuracy in both diseases. The results of immunohistochemistry showed that ABCC5 and TUBG1 were significantly overexpressed in NAFLD and HCC tissues compared with normal liver tissues. The Oil Red O staining and triglyceride identified the successful construction of HepG2 and LO2 high-fat models using PA/OA. The results of RT-qPCR showed that the lipidization of LO2 and HepG2 increased the mRNA expression of ABCC5. CONCLUSIONS: The gene model constructed by ABCC5 and TUBG1 has high sensibility and veracity in the diagnosis of NAFLD as well as the diagnosis and prognosis of HCC. ABCC5 and TUBG1 may play an important role in the development of NAFLD to HCC. In addition, lipidization could upregulate the mRNA expression of ABCC5 in HCC.
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spelling pubmed-94106242022-08-26 Screening of co-pathogenic genes of non-alcoholic fatty liver disease and hepatocellular carcinoma Chen, Ting Zhang, Siwen Zhou, Dongmei Lu, Peipei Mo, Xianglai Tamrakar, Rashi Yang, Xi Front Oncol Oncology BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a risk factor for hepatocellular carcinoma (HCC). However, its carcinogenic mechanism is still unclear, looking for both diseases’ transcriptome levels, the same changes as we are looking for NAFLD may provide a potential mechanism of action of HCC. Thus, our study aimed to discover the coexisting pathogenic genes of NAFLD and HCC. METHODS: We performed a variance analysis with public data for both diseases. At the same time, weighted gene correlation network analysis (WGCNA) was used to find highly correlated gene modules in both diseases. The darkturquoise gene module was found to be highly correlated with both diseases. Based on the diagnosis related module genes and the differential genes of the two diseases, we constructed diagnostic and prognostic models by logistic regression, univariate Cox regression, and LASSO regression. Public datasets verified the results. Meanwhile, we built a competing endogenous RNA (ceRNA) network based on the model genes and explored the related pathways and immune correlation involved in the two diseases by using Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and gene set enrichment analyses. Immunohistochemistry was used to verify the different expression of ABCC5 and TUBG1 among the normal liver, NAFLD, and HCC tissues. Sodium palmitate/sodium oleate was used to establish high-fat cell models, and Real Time Quantitative Polymerase Chain Reaction (RT-qPCR) was used to verify the messenger RNA (mRNA) expression of ABCC5 in lipidization cells. RESULTS: A total of 26 upregulated genes and 87 downregulated genes were found using limma package identification analysis. According to WGCNA, the darkturquoise gene module was highly correlated with the prognosis of both diseases. The coexisting genes acquired by the two groups were only three central genes, that is, ABCC5, DHODH and TUBG1. The results indicated that the diagnostic and prognostic models constructed by ABCC5 and TUBG1 genes had high accuracy in both diseases. The results of immunohistochemistry showed that ABCC5 and TUBG1 were significantly overexpressed in NAFLD and HCC tissues compared with normal liver tissues. The Oil Red O staining and triglyceride identified the successful construction of HepG2 and LO2 high-fat models using PA/OA. The results of RT-qPCR showed that the lipidization of LO2 and HepG2 increased the mRNA expression of ABCC5. CONCLUSIONS: The gene model constructed by ABCC5 and TUBG1 has high sensibility and veracity in the diagnosis of NAFLD as well as the diagnosis and prognosis of HCC. ABCC5 and TUBG1 may play an important role in the development of NAFLD to HCC. In addition, lipidization could upregulate the mRNA expression of ABCC5 in HCC. Frontiers Media S.A. 2022-08-11 /pmc/articles/PMC9410624/ /pubmed/36033523 http://dx.doi.org/10.3389/fonc.2022.911808 Text en Copyright © 2022 Chen, Zhang, Zhou, Lu, Mo, Tamrakar and Yang https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Chen, Ting
Zhang, Siwen
Zhou, Dongmei
Lu, Peipei
Mo, Xianglai
Tamrakar, Rashi
Yang, Xi
Screening of co-pathogenic genes of non-alcoholic fatty liver disease and hepatocellular carcinoma
title Screening of co-pathogenic genes of non-alcoholic fatty liver disease and hepatocellular carcinoma
title_full Screening of co-pathogenic genes of non-alcoholic fatty liver disease and hepatocellular carcinoma
title_fullStr Screening of co-pathogenic genes of non-alcoholic fatty liver disease and hepatocellular carcinoma
title_full_unstemmed Screening of co-pathogenic genes of non-alcoholic fatty liver disease and hepatocellular carcinoma
title_short Screening of co-pathogenic genes of non-alcoholic fatty liver disease and hepatocellular carcinoma
title_sort screening of co-pathogenic genes of non-alcoholic fatty liver disease and hepatocellular carcinoma
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9410624/
https://www.ncbi.nlm.nih.gov/pubmed/36033523
http://dx.doi.org/10.3389/fonc.2022.911808
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