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Cross Analysis of Genomic-Pathologic Features on Multiple Primary Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is a prevalent malignancy cancer worldwide with a poor prognosis. Hepatic resection is indicated as a potentially curative option for HCC patients in the early stage. However, due to multiple nodules, it leads to clinical challenges for surgical management. Approximate...

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Autores principales: Ren, Fei, Wang, Depin, Zhang, Xueyuan, Zhao, Na, Wang, Xiaowen, Zhang, Yu, Li, Li
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9251469/
https://www.ncbi.nlm.nih.gov/pubmed/35795211
http://dx.doi.org/10.3389/fgene.2022.846517
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author Ren, Fei
Wang, Depin
Zhang, Xueyuan
Zhao, Na
Wang, Xiaowen
Zhang, Yu
Li, Li
author_facet Ren, Fei
Wang, Depin
Zhang, Xueyuan
Zhao, Na
Wang, Xiaowen
Zhang, Yu
Li, Li
author_sort Ren, Fei
collection PubMed
description Hepatocellular carcinoma (HCC) is a prevalent malignancy cancer worldwide with a poor prognosis. Hepatic resection is indicated as a potentially curative option for HCC patients in the early stage. However, due to multiple nodules, it leads to clinical challenges for surgical management. Approximately 41%–75% of HCC cases are multifocal at initial diagnosis, which may arise from multicentric occurrence (MO-HCC) or intrahepatic metastasis (IM-HCC) pattern with significantly different clinical outcomes. Effectively differentiating the two mechanisms is crucial to prioritize the allocation of surgery for multifocal HCC. In this study, we collected a multifocal hepatocellular carcinoma cohort of 17 patients with a total of 34 samples. We performed whole-exome sequencing and staining of pathological HE sections for each lesion. Reconstruction of the clonal evolutionary pattern using genome mutations showed that the intrahepatic metastogenesis pattern had a poorer survival performance than independent origins, with variants in the TP53, ARID1A, and higher CNV variants occurring more significantly in the metastatic pattern. Cross-modality analysis with pathology showed that molecular classification results were consistent with pathology results in 70.6% of patients, and we found that pathology results could further complement the classification for undefined patterns of occurrence. Based on these results, we propose a model to differentiate the pattern of multifocal hepatocellular carcinoma based on the pathological results and genome mutations information, which can provide guidelines for diagnosing and treating multifocal hepatocellular carcinoma.
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spelling pubmed-92514692022-07-05 Cross Analysis of Genomic-Pathologic Features on Multiple Primary Hepatocellular Carcinoma Ren, Fei Wang, Depin Zhang, Xueyuan Zhao, Na Wang, Xiaowen Zhang, Yu Li, Li Front Genet Genetics Hepatocellular carcinoma (HCC) is a prevalent malignancy cancer worldwide with a poor prognosis. Hepatic resection is indicated as a potentially curative option for HCC patients in the early stage. However, due to multiple nodules, it leads to clinical challenges for surgical management. Approximately 41%–75% of HCC cases are multifocal at initial diagnosis, which may arise from multicentric occurrence (MO-HCC) or intrahepatic metastasis (IM-HCC) pattern with significantly different clinical outcomes. Effectively differentiating the two mechanisms is crucial to prioritize the allocation of surgery for multifocal HCC. In this study, we collected a multifocal hepatocellular carcinoma cohort of 17 patients with a total of 34 samples. We performed whole-exome sequencing and staining of pathological HE sections for each lesion. Reconstruction of the clonal evolutionary pattern using genome mutations showed that the intrahepatic metastogenesis pattern had a poorer survival performance than independent origins, with variants in the TP53, ARID1A, and higher CNV variants occurring more significantly in the metastatic pattern. Cross-modality analysis with pathology showed that molecular classification results were consistent with pathology results in 70.6% of patients, and we found that pathology results could further complement the classification for undefined patterns of occurrence. Based on these results, we propose a model to differentiate the pattern of multifocal hepatocellular carcinoma based on the pathological results and genome mutations information, which can provide guidelines for diagnosing and treating multifocal hepatocellular carcinoma. Frontiers Media S.A. 2022-06-20 /pmc/articles/PMC9251469/ /pubmed/35795211 http://dx.doi.org/10.3389/fgene.2022.846517 Text en Copyright © 2022 Ren, Wang, Zhang, Zhao, Wang, Zhang and Li. 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 Genetics
Ren, Fei
Wang, Depin
Zhang, Xueyuan
Zhao, Na
Wang, Xiaowen
Zhang, Yu
Li, Li
Cross Analysis of Genomic-Pathologic Features on Multiple Primary Hepatocellular Carcinoma
title Cross Analysis of Genomic-Pathologic Features on Multiple Primary Hepatocellular Carcinoma
title_full Cross Analysis of Genomic-Pathologic Features on Multiple Primary Hepatocellular Carcinoma
title_fullStr Cross Analysis of Genomic-Pathologic Features on Multiple Primary Hepatocellular Carcinoma
title_full_unstemmed Cross Analysis of Genomic-Pathologic Features on Multiple Primary Hepatocellular Carcinoma
title_short Cross Analysis of Genomic-Pathologic Features on Multiple Primary Hepatocellular Carcinoma
title_sort cross analysis of genomic-pathologic features on multiple primary hepatocellular carcinoma
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9251469/
https://www.ncbi.nlm.nih.gov/pubmed/35795211
http://dx.doi.org/10.3389/fgene.2022.846517
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