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Stratification of Hepatocellular Carcinoma Patients Based on Acetate Utilization

Elias Björnson (Institutionen för biologi och bioteknik, Systembiologi) ; B. Mukhopadhyay ; A. Asplund ; N. Pristovsek ; R. Cinar ; Stefano Romeo ; M. Uhlen ; G. Kunos ; Jens B. Nielsen (Institutionen för biologi och bioteknik, Systembiologi) ; Adil Mardinoglu (Institutionen för biologi och bioteknik, Systembiologi)
Cell Reports (2211-1247). Vol. 13 (2015), 9, p. 2014-2026.
[Artikel, refereegranskad vetenskaplig]

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.



Denna post skapades 2016-01-07. Senast ändrad 2016-01-27.
CPL Pubid: 230007

 

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Institutioner (Chalmers)

Institutionen för biologi och bioteknik, Systembiologi
Wallenberglaboratoriet (GU)
Center for Cardiovascular and Metabolic Research (CMR) (GU)
Institutionen för medicin, avdelningen för molekylär och klinisk medicin (GU)

Ämnesområden

Cellbiologi

Chalmers infrastruktur