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Etiology-Specific Analysis of Hepatocellular Carcinoma Transcriptome Reveals Genetic Dysregulation in Pathways Implicated in Immunotherapy Efficacy.
Li, Wei Tse; Zou, Angela E; Honda, Christine O; Zheng, Hao; Wang, Xiao Qi; Kisseleva, Tatiana; Chang, Eric Y; Ongkeko, Weg M.
Afiliação
  • Li WT; Department of Surgery, University of California, San Diego, CA 92093, USA.
  • Zou AE; Department of Surgery, University of California, San Diego, CA 92093, USA.
  • Honda CO; Department of Surgery, University of California, San Diego, CA 92093, USA.
  • Zheng H; Department of Surgery, University of California, San Diego, CA 92093, USA.
  • Wang XQ; Department of Surgery, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong, China.
  • Kisseleva T; Department of Surgery, University of California, San Diego, CA 92093, USA.
  • Chang EY; Department of Radiology, California and Radiology Service, VA San Diego Healthcare System, University of California, San Diego, CA 92093, USA.
  • Ongkeko WM; Department of Surgery, University of California, San Diego, CA 92093, USA. wongkeko@ucsd.edu.
Cancers (Basel) ; 11(9)2019 Aug 30.
Article em En | MEDLINE | ID: mdl-31480259
Immunotherapy has emerged in recent years as arguably the most effective treatment for advanced hepatocellular carcinoma (HCC), but the failure of a large percentage of patients to respond to immunotherapy remains as the ultimate obstacle to successful treatment. Etiology-associated dysregulation of immune-associated (IA) genes may be central to the development of this differential clinical response. We identified immune-associated genes potentially dysregulated by alcohol or viral hepatitis B in HCC and validated alcohol-induced dysregulations in vitro while using large-scale RNA-sequencing data from The Cancer Genome Atlas (TCGA). Thirty-four clinically relevant dysregulated IA genes were identified. We profiled the correlation of all genomic alterations in HCC patients to IA gene expression while using the information theory-based algorithm REVEALER to investigate the molecular mechanism for their dysregulation and explore the possibility of genome-based patient stratification. We also studied gene expression regulators and identified multiple microRNAs that were implicated in HCC pathogenesis that can potentially regulate these IA genes' expression. Our study identified potential key pathways, including the IL-7 signaling pathway and TNFRSF4 (OX40)- NF-κB pathway, to target in immunotherapy treatments and presents microRNAs as promising therapeutic targets for dysregulated IA genes because of their extensive regulatory roles in the cancer immune landscape.
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Texto completo: 1 Base de dados: MEDLINE Tipo de estudo: Etiology_studies Idioma: En Ano de publicação: 2019 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Tipo de estudo: Etiology_studies Idioma: En Ano de publicação: 2019 Tipo de documento: Article