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Network Analysis Reveals Heterogeneous Response of Redox Metabolism in Hepatocellular Carcinoma Patients

48 Pages Posted: 18 Jul 2018 Sneak Peek Status: Under Review

See all articles by Rui Benfeitas

Rui Benfeitas

Royal Institute of Technology (KTH) - Science for Life Laboratory

Gholamreza Bidkhori

Royal Institute of Technology (KTH) - Science for Life Laboratory

Bani Mukhopadhyay

National Institutes of Health - Laboratory of Physiologic Studies

Martina Klevstig

Göteborg University - Department of Molecular and Clinical Medicine

Muhammad Arif

Royal Institute of Technology (KTH) - Science for Life Laboratory

Cheng Zhang

Royal Institute of Technology (KTH) - Science for Life Laboratory

Sunjae Lee

Royal Institute of Technology (KTH) - Science for Life Laboratory

Resat Cinar

Royal Institute of Technology (KTH) - Science for Life Laboratory

Jens Nielsen

Chalmers University of Technology - Department of Biology and Biological Engineering

Mathias Uhlen

Royal Institute of Technology (KTH) - Science for Life Laboratory

Jan Boren

Göteborg University - Department of Molecular and Clinical Medicine

George Kunos

National Institutes of Health - Laboratory of Physiologic Studies

Adil Mardinoglu

Royal Institute of Technology (KTH) - Science for Life Laboratory

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Abstract

Redox metabolism is often considered for cancer treatment but a systematic examination of redox behavior in hepatocellular carcinoma (HCC) is missing. We employed systems biology approaches to identify key features in redox metabolism in HCC. Several redox genes, including novel prognostic markers, are co-expressed with liver-specific, immune and inflammation genes. HCC also display antagonistic redox behavior, associated with altered fatty acid and amino acid metabolisms, differentiation, proliferation, and antioxidant defense. These responses are observed at the transcriptomic, metabolomic and protein levels, validated in independent cohorts, and experimentally observed using mice transcriptomics. Our integrative approach highlights mechanistic differences associated with HCC subtypes and progression, enabling tumor stratification and identification of survival signatures and potential therapeutic targets in redox metabolism.

Suggested Citation

Benfeitas, Rui and Bidkhori, Gholamreza and Mukhopadhyay, Bani and Klevstig, Martina and Arif, Muhammad and Zhang, Cheng and Lee, Sunjae and Cinar, Resat and Nielsen, Jens and Uhlen, Mathias and Boren, Jan and Kunos, George and Mardinoglu, Adil, Network Analysis Reveals Heterogeneous Response of Redox Metabolism in Hepatocellular Carcinoma Patients (2018). Available at SSRN: https://ssrn.com/abstract=3215903 or http://dx.doi.org/10.2139/ssrn.3215903
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Rui Benfeitas (Contact Author)

Royal Institute of Technology (KTH) - Science for Life Laboratory ( email )

Stockholm, SE-100 44
Sweden

Gholamreza Bidkhori

Royal Institute of Technology (KTH) - Science for Life Laboratory ( email )

Stockholm, SE-100 44
Sweden

Bani Mukhopadhyay

National Institutes of Health - Laboratory of Physiologic Studies ( email )

9000 Rockville Pike
Bethesda, MD 20892
United States

Martina Klevstig

Göteborg University - Department of Molecular and Clinical Medicine ( email )

PO Box 400
Göteborg, SE405 30
Sweden

Muhammad Arif

Royal Institute of Technology (KTH) - Science for Life Laboratory ( email )

Stockholm, SE-100 44
Sweden

Cheng Zhang

Royal Institute of Technology (KTH) - Science for Life Laboratory ( email )

Stockholm, SE-100 44
Sweden

Sunjae Lee

Royal Institute of Technology (KTH) - Science for Life Laboratory ( email )

Stockholm, SE-100 44
Sweden

Resat Cinar

Royal Institute of Technology (KTH) - Science for Life Laboratory ( email )

Stockholm, SE-100 44
Sweden

Jens Nielsen

Chalmers University of Technology - Department of Biology and Biological Engineering ( email )

SE-412 96 Goteborg
Sweden

Mathias Uhlen

Royal Institute of Technology (KTH) - Science for Life Laboratory ( email )

Stockholm, SE-100 44
Sweden

Jan Boren

Göteborg University - Department of Molecular and Clinical Medicine ( email )

PO Box 400
Göteborg, SE405 30
Sweden

George Kunos

National Institutes of Health - Laboratory of Physiologic Studies ( email )

9000 Rockville Pike
Bethesda, MD 20892
United States

Adil Mardinoglu

Royal Institute of Technology (KTH) - Science for Life Laboratory ( email )

Stockholm, SE-100 44
Sweden

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