Transcriptomic and Proteomic Analysis of Steatohepatitic Hepatocellular Carcinoma Reveals Novel Distinct Biologic Features

Benjamin J Van Treeck; Taofic Mounajjed; Roger K Moreira; Mushfig Orujov; Daniela S Allende; Andrew M Bellizzi; Stephen M Lagana; Jaime I Davila; Erik Jessen; Rondell P Graham

doi:10.1093/ajcp/aqaa114

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Transcriptomic and Proteomic Analysis of Steatohepatitic Hepatocellular Carcinoma Reveals Novel Distinct Biologic Features

Journal article

Peer reviewed

Transcriptomic and Proteomic Analysis of Steatohepatitic Hepatocellular Carcinoma Reveals Novel Distinct Biologic Features

Benjamin J Van Treeck, Taofic Mounajjed, Roger K Moreira, Mushfig Orujov, Daniela S Allende, Andrew M Bellizzi, Stephen M Lagana, Jaime I Davila, Erik Jessen and Rondell P Graham

American journal of clinical pathology, Vol.155(1), pp.87-96

01/04/2021

DOI: 10.1093/ajcp/aqaa114

PMID: 32885245

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Abstract

Steatohepatitic hepatocellular carcinoma is a distinct variant of hepatocellular carcinoma strongly associated with underlying nonalcoholic steatohepatitis. The molecular biology of steatohepatitic hepatocellular carcinoma is not fully elucidated, and thus we aimed to investigate the molecular underpinnings of this entity. Transcriptomic analysis using RNAseq was performed on eight tumor-nonneoplastic pairs of steatohepatitic hepatocellular carcinoma with comparison to conventional hepatocellular carcinoma transcriptomes curated in The Cancer Genome Atlas. Immunohistochemistry was used to validate key RNA-level findings. Steatohepatitic hepatocellular carcinoma demonstrated a distinctive differential gene expression profile compared with The Cancer Genome Atlas curated conventional hepatocellular carcinomas (n = 360 cases), indicating the distinctive steatohepatitic hepatocellular carcinoma morphology is associated with a unique gene expression profile. Pathway analysis comparing tumor-nonneoplastic pairs revealed significant upregulation of the hedgehog pathway based on GLI1 overexpression and significant downregulation of carnitine palmitoyltransferase 2 transcript. Glutamine synthetase transcript was significantly upregulated, and fatty acid binding protein 1 transcript was significantly downregulated and immunohistochemically confirmed, indicating steatohepatitic hepatocellular carcinoma tumor cells display a zone 3 phenotype. Steatohepatitic hepatocellular carcinoma demonstrates a distinctive morphology and gene expression profile, phenotype of zone 3 hepatocytes, and activation of the hedgehog pathway and repression of carnitine palmitoyltransferase 2, which may be important in tumorigenesis.

Immunohistochemistry

Proteomics

Adult

Aged

Biomarkers, Tumor - genetics

Biomarkers, Tumor - metabolism

Carcinoma, Hepatocellular - genetics

Carcinoma, Hepatocellular - metabolism

Carcinoma, Hepatocellular - pathology

Fatty Liver - genetics

Fatty Liver - metabolism

Fatty Liver - pathology

Female

Gene Expression Profiling

Humans

Liver - metabolism

Liver - pathology

Liver Neoplasms - genetics

Liver Neoplasms - metabolism

Liver Neoplasms - pathology

Male

Middle Aged

Proteome

Transcriptome

Details

Title: Subtitle: Transcriptomic and Proteomic Analysis of Steatohepatitic Hepatocellular Carcinoma Reveals Novel Distinct Biologic Features
Creators: Benjamin J Van Treeck - Mayo Clinic
Taofic Mounajjed - Mayo Clinic
Roger K Moreira - Mayo Clinic
Mushfig Orujov - Cleveland Clinic
Daniela S Allende - Cleveland Clinic
Andrew M Bellizzi - University of Iowa
Stephen M Lagana - Columbia University
Jaime I Davila - Mayo Clinic
Erik Jessen - Mayo Clinic
Rondell P Graham - Mayo Clinic
Resource Type: Journal article
Publication Details: American journal of clinical pathology, Vol.155(1), pp.87-96
DOI: 10.1093/ajcp/aqaa114
PMID: 32885245
ISSN: 0002-9173
eISSN: 1943-7722
Language: English
Date published: 01/04/2021
Academic Unit: Pathology
Record Identifier: 9984183987502771

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