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Identification of Driver Genes Regulating the T-Cell–Infiltrating Levels in Hepatocellular Carcinoma

The driver genes regulating T-cell infiltration are important for understanding immune-escape mechanisms and developing more effective immunotherapy. However, researches in this field have rarely been reported in hepatocellular carcinoma (HCC). In the present study, we identified cancer driver genes...

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Autores principales: Cai, Yi, Tian, Ying, Wang, Jianchu, Wei, Wang, Tang, Qianli, Lu, Libai, Luo, Zongjiang, Li, Wenchuan, Lu, Yuan, Pu, Jian, Yang, Zhengxia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7767976/
https://www.ncbi.nlm.nih.gov/pubmed/33381145
http://dx.doi.org/10.3389/fgene.2020.560546
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author Cai, Yi
Tian, Ying
Wang, Jianchu
Wei, Wang
Tang, Qianli
Lu, Libai
Luo, Zongjiang
Li, Wenchuan
Lu, Yuan
Pu, Jian
Yang, Zhengxia
author_facet Cai, Yi
Tian, Ying
Wang, Jianchu
Wei, Wang
Tang, Qianli
Lu, Libai
Luo, Zongjiang
Li, Wenchuan
Lu, Yuan
Pu, Jian
Yang, Zhengxia
author_sort Cai, Yi
collection PubMed
description The driver genes regulating T-cell infiltration are important for understanding immune-escape mechanisms and developing more effective immunotherapy. However, researches in this field have rarely been reported in hepatocellular carcinoma (HCC). In the present study, we identified cancer driver genes triggered by copy number alterations such as CDKN2B, MYC, TSC1, TP53, and GSK3B. The T-cell infiltration levels were significantly decreased in both HCC and recurrent HCC tissues compared with the adjacent normal liver tissues. Remarkably, we identified that copy number losses of MAX and TP53 were candidate driver genes that significantly suppress T-cell infiltration in HCC. Accordingly, their downstream oncogenic pathway, cell cycle, was significantly activated in the low T-cell infiltration HCC. Moreover, the chemokine-related target genes by TP53, which played key roles in T-cell recruitment, were also downregulated in HCC with TP53/MAX deletions, suggesting that copy number losses in MAX and TP53 might result in T-cell depletion in HCC via downregulating chemokines. Clinically, the T-cell infiltration levels and chemokines activity could accurately predict the response of sorafenib, and the prognostic outcomes in HCC. In conclusion, the systematic analysis not only facilitates identification of driver genes and signaling pathways involved in T-cell infiltration and immune escape, but also gains more insights into the functional roles of T cells in HCC.
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spelling pubmed-77679762020-12-29 Identification of Driver Genes Regulating the T-Cell–Infiltrating Levels in Hepatocellular Carcinoma Cai, Yi Tian, Ying Wang, Jianchu Wei, Wang Tang, Qianli Lu, Libai Luo, Zongjiang Li, Wenchuan Lu, Yuan Pu, Jian Yang, Zhengxia Front Genet Genetics The driver genes regulating T-cell infiltration are important for understanding immune-escape mechanisms and developing more effective immunotherapy. However, researches in this field have rarely been reported in hepatocellular carcinoma (HCC). In the present study, we identified cancer driver genes triggered by copy number alterations such as CDKN2B, MYC, TSC1, TP53, and GSK3B. The T-cell infiltration levels were significantly decreased in both HCC and recurrent HCC tissues compared with the adjacent normal liver tissues. Remarkably, we identified that copy number losses of MAX and TP53 were candidate driver genes that significantly suppress T-cell infiltration in HCC. Accordingly, their downstream oncogenic pathway, cell cycle, was significantly activated in the low T-cell infiltration HCC. Moreover, the chemokine-related target genes by TP53, which played key roles in T-cell recruitment, were also downregulated in HCC with TP53/MAX deletions, suggesting that copy number losses in MAX and TP53 might result in T-cell depletion in HCC via downregulating chemokines. Clinically, the T-cell infiltration levels and chemokines activity could accurately predict the response of sorafenib, and the prognostic outcomes in HCC. In conclusion, the systematic analysis not only facilitates identification of driver genes and signaling pathways involved in T-cell infiltration and immune escape, but also gains more insights into the functional roles of T cells in HCC. Frontiers Media S.A. 2020-12-14 /pmc/articles/PMC7767976/ /pubmed/33381145 http://dx.doi.org/10.3389/fgene.2020.560546 Text en Copyright © 2020 Cai, Tian, Wang, Wei, Tang, Lu, Luo, Li, Lu, Pu and Yang. http://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
Cai, Yi
Tian, Ying
Wang, Jianchu
Wei, Wang
Tang, Qianli
Lu, Libai
Luo, Zongjiang
Li, Wenchuan
Lu, Yuan
Pu, Jian
Yang, Zhengxia
Identification of Driver Genes Regulating the T-Cell–Infiltrating Levels in Hepatocellular Carcinoma
title Identification of Driver Genes Regulating the T-Cell–Infiltrating Levels in Hepatocellular Carcinoma
title_full Identification of Driver Genes Regulating the T-Cell–Infiltrating Levels in Hepatocellular Carcinoma
title_fullStr Identification of Driver Genes Regulating the T-Cell–Infiltrating Levels in Hepatocellular Carcinoma
title_full_unstemmed Identification of Driver Genes Regulating the T-Cell–Infiltrating Levels in Hepatocellular Carcinoma
title_short Identification of Driver Genes Regulating the T-Cell–Infiltrating Levels in Hepatocellular Carcinoma
title_sort identification of driver genes regulating the t-cell–infiltrating levels in hepatocellular carcinoma
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7767976/
https://www.ncbi.nlm.nih.gov/pubmed/33381145
http://dx.doi.org/10.3389/fgene.2020.560546
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