Stratification of Hepatocellular Carcinoma Patients Based on Acetate Utilization
Journal article, 2015

Hepatocellular carcinoma (HCC) is a deadly form of liver cancer that is increasingly prevalent. We analyzed global gene expression profiling of 361 HCC tumors and 49 adjacent noncancerous liver samples by means of combinatorial network-based analysis. We investigated the correlation between transcriptome and proteome of HCC and reconstructed a functional genome-scale metabolic model (GEM) for HCC. We identified fundamental metabolic processes required for cell proliferation using the network centric view provided by the GEM. Our analysis revealed tight regulation of fatty acid biosynthesis (FAB) and highly significant deregulation of fatty acid oxidation in HCC. We predicted mitochondrial acetate as an emerging substrate for FAB through upregulation of mitochondrial acetyl-CoA synthetase (ACSS1) in HCC. We analyzed heterogeneous expression of ACSS1 and ACSS2 between HCC patients stratified by high and low ACSS1 and ACSS2 expression and revealed that ACSS1 is associated with tumor growth and malignancy under hypoxic conditions in human HCC.

Author

Elias Björnson

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

B. Mukhopadhyay

National Institute on Alcohol Abuse and Alcoholism

A. Asplund

Uppsala University

N. Pristovsek

Uppsala University

R. Cinar

National Institute on Alcohol Abuse and Alcoholism

Stefano Romeo

University of Gothenburg

M. Uhlen

Royal Institute of Technology (KTH)

G. Kunos

National Institute on Alcohol Abuse and Alcoholism

Jens B Nielsen

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

Adil Mardinoglu

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

Cell Reports

2211-1247 (ISSN)

Vol. 13 9 2014-2026

Subject Categories

Cell and Molecular Biology

Areas of Advance

Life Science Engineering (2010-2018)

DOI

10.1016/j.celrep.2015.10.045

More information

Latest update

2/28/2018