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Transcriptional Landscape of Hepatocellular Carcinoma Reveals that Patient Ethnic-Origin Influences Patterns of Expression

View ORCID ProfileRachel Zayas, View ORCID ProfileArtemio Sisson III, Ariana Kuhnsman, View ORCID ProfileBolni Marius Nagalo, Lewis R. Roberts, Kenneth Buetow
doi: https://doi.org/10.1101/2020.12.01.404285
Rachel Zayas
1Active Genomes Expressed (AGED) Diagnostics, Washington, DC
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  • For correspondence: Nagalo.bolni@mayo.edu Rachel@ageddiagnostics.com
Artemio Sisson III
1Active Genomes Expressed (AGED) Diagnostics, Washington, DC
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Ariana Kuhnsman
1Active Genomes Expressed (AGED) Diagnostics, Washington, DC
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Bolni Marius Nagalo
1Active Genomes Expressed (AGED) Diagnostics, Washington, DC
2Division of Hematology and Medical Oncology, Mayo Clinic, Arizona, Phoenix
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  • For correspondence: Nagalo.bolni@mayo.edu Rachel@ageddiagnostics.com
Lewis R. Roberts
3Division of Gastroenterology and Hepatology Mayo Clinic in Minnesota, Rochester
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Kenneth Buetow
4Computational Sciences and Informatics program for Complex Adaptive Systems, Arizona State University, Arizona, Tempe
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Abstract

The global incidence of hepatocellular carcinoma (HCC) has increased threefold in the last 30 years. In the United States, individuals with ancestry from Asia, Africa and Latin America have a significantly higher risk of developing HCC. However, the molecular mechanisms by which HCC disparities occur remain mostly understudied. Herein, we employed advanced bioinformatics analysis tools to identify genomic drivers that could explain the differences seen among HCC patients of distinct ethnicities (geographic origins). Data from TCGA and open-source software tools HiSTAT, StringTie, and Ballgown were used to map next-generation sequencing (NGS) reads from DNA and RNA, assemble transcripts, and quantify gene abundance. Differential genes/transcripts were mapped to known biomarkers and targets of systemic HCC therapeutics. Four overlapping transcripts were identified between each ethnicity group: FCN2, FCN3, COLEC10, and GDF2. However, we also found that multiple genes are expressed in an ethnicity-specific manner. Our models also revealed that both current and emerging biomarkers fail to capture heterogeneity between patients of different ethnicities. Finally, we have determined that first-line treatment, such as Sorafenib, may be better suited for Asian patients, while Lenvatinib may exhibit better efficacy for Caucasian patients. In conclusion, we have outlined that the pathways involved in early hepatocarcinogenesis may occur in an ethnicity-specific manner and that these distinct phenotypes should be taken into account for biomarker and therapeutic development.

Competing Interest Statement

AGED Diagnostics.

Footnotes

  • Potential conflict of interest: Nothing to report.

  • Financial Support: This work was supported by AGED Diagnostics.

  • Resources: The results shown here are in part based upon data generated by the TCGA Research Network: https://www.cancer.gov/tcga.

  • The Genotype-Tissue Expression (GTEx) Project was supported by the Common Fund of the Office of the Director of the National Institutes of Health, and by NCI, NHGRI, NHLBI, NIDA, NIMH, and NINDS. The data used for the analyses described in this manuscript were obtained from: the GTEx Portal on 09/04/2020 and/or dbGaP accession number phs000424.vN.pN on 09/04/2020.

  • Abbreviations

    HBV
    hepatitis B virus
    HCC
    hepatocellular carcinoma
    HCV
    hepatitis C virus
    NAFLD
    Nonalcoholic fatty liver disease
    NASH
    Nonalcoholic steatohepatitis
    LIHC
    Liver Hepatocellular Carcinoma
    PNPLA3
    polymorphisms in adiponutrin 3
    GCKR
    Glucokinase Regulator
    TCGA
    The Cancer Genome Atlas
    RNA-Seq
    RNA-sequencing
    CGC
    Cancer Genomics Cloud
    AJCC
    American Joint Committee on Cancer
    SPP1
    osteopontin
    GOLM1
    Golgi Membrane Protein
    MDK
    midkine
    DKK1
    Dickkopf-1
    GPC3
    glycoprotein-3
    F2
    coagulation factor II
    DCPS
    Decapping Enzyme Scavenger
    FUCA1
    alpha-1-fucosidase
    AFP
    alpha fetoprotein
  • Copyright 
    The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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    Transcriptional Landscape of Hepatocellular Carcinoma Reveals that Patient Ethnic-Origin Influences Patterns of Expression
    Rachel Zayas, Artemio Sisson III, Ariana Kuhnsman, Bolni Marius Nagalo, Lewis R. Roberts, Kenneth Buetow
    bioRxiv 2020.12.01.404285; doi: https://doi.org/10.1101/2020.12.01.404285
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    Transcriptional Landscape of Hepatocellular Carcinoma Reveals that Patient Ethnic-Origin Influences Patterns of Expression
    Rachel Zayas, Artemio Sisson III, Ariana Kuhnsman, Bolni Marius Nagalo, Lewis R. Roberts, Kenneth Buetow
    bioRxiv 2020.12.01.404285; doi: https://doi.org/10.1101/2020.12.01.404285

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