Stratification of Hepatocellular Carcinoma Patients Based on Acetate Utilization
Artikel i vetenskaplig tidskrift, 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.

Författare

Elias Björnson

Chalmers, Biologi och bioteknik, Systembiologi

B. Mukhopadhyay

National Institute on Alcohol Abuse and Alcoholism

A. Asplund

Uppsala universitet

N. Pristovsek

Uppsala universitet

R. Cinar

National Institute on Alcohol Abuse and Alcoholism

Stefano Romeo

Göteborgs universitet

M. Uhlen

Kungliga Tekniska Högskolan (KTH)

G. Kunos

National Institute on Alcohol Abuse and Alcoholism

Jens B Nielsen

Chalmers, Biologi och bioteknik, Systembiologi

Adil Mardinoglu

Chalmers, Biologi och bioteknik, Systembiologi

Cell Reports

2211-1247 (ISSN)

Vol. 13 2014-2026

Ämneskategorier

Cell- och molekylärbiologi

Styrkeområden

Livsvetenskaper och teknik

DOI

10.1016/j.celrep.2015.10.045