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Characterization of...
Characterization of heterogeneous redox responses in hepatocellular carcinoma patients using network analysis
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- Benfeitas, Rui (author)
- KTH,Science for Life Laboratory, SciLifeLab
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- Bidkhori, Gholamreza (author)
- KTH,Science for Life Laboratory, SciLifeLab
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- Mukhopadhyay, B. (author)
- National Institute on Alcohol Abuse and Alcoholism,NIAAA, Lab Physiol Studies, NIH, Bethesda, MD USA.
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- Klevstig, Martina (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine,Sahlgrenska universitetssjukhuset,Sahlgrenska University Hospital,Univ Gothenburg, Sahlgrenska Univ Hosp, Dept Mol & Clin Med, Gothenburg, Sweden.
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- Arif, Muhammad (author)
- KTH,Systembiologi,Science for Life Laboratory, SciLifeLab
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- Zhang, C. (author)
- KTH,Science for Life Laboratory, SciLifeLab,Systembiologi
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- Lee, Sunjae (author)
- KTH,Science for Life Laboratory, SciLifeLab
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- Cinar, R. (author)
- National Institute on Alcohol Abuse and Alcoholism,NIAAA, Lab Physiol Studies, NIH, Bethesda, MD USA.
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- Nielsen, Jens B, 1962 (author)
- Chalmers tekniska högskola,Chalmers University of Technology,Chalmers Univ Technol, Dept Biol & Biol Engn, Gothenburg, Sweden.
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- Uhlén, Mathias (author)
- KTH,Systembiologi
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- Borén, Jan, 1963 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine,Sahlgrenska universitetssjukhuset,Sahlgrenska University Hospital,Univ Gothenburg, Sahlgrenska Univ Hosp, Dept Mol & Clin Med, Gothenburg, Sweden.
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- Kunos, G. (author)
- National Institute on Alcohol Abuse and Alcoholism,NIAAA, Lab Physiol Studies, NIH, Bethesda, MD USA.
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- Mardinoglu, Adil, 1982 (author)
- KTH,Science for Life Laboratory, SciLifeLab,Sci Life Lab, SE-17121 Stockholm, Sweden.
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(creator_code:org_t)
- Elsevier BV, 2019
- 2019
- English.
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In: Ebiomedicine. - : Elsevier BV. - 2352-3964. ; 40, s. 471-487
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Abstract
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- Background: Redox metabolism is often considered a potential target for cancer treatment, but a systematic examination of redox responses in hepatocellular carcinoma (HCC) is missing. Methods: Here, we employed systems biology and biological network analyses to reveal key roles of genes associated with redox metabolism in HCC by integrating multi-omics data. Findings: We found that several redox genes, including 25 novel potential prognostic genes, are significantly co-expressed with liver-specific genes and genes associated with immunity and inflammation. Based on an integrative analysis, we found that HCC tumors display antagonistic behaviors in redox responses. The two HCC groups are associated with altered fatty acid, amino acid, drug and hormone metabolism, differentiation, proliferation, and NADPH-independent vs - dependent antioxidant defenses. Redox behavior varies with known tumor subtypes and progression, affecting patient survival. These antagonistic responses are also displayed at the protein and metabolite level and were validated in several independent cohorts. We finally showed the differential redox behavior using mice transcriptomics in HCC and noncancerous tissues and associated with hypoxic features of the two redox gene groups. Interpretation: Our integrative approaches highlighted mechanistic differences among tumors and allowed the identification of a survival signature and several potential therapeutic targets for the treatment of HCC.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
- NATURVETENSKAP -- Biologi -- Bioinformatik och systembiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Bioinformatics and Systems Biology (hsv//eng)
- NATURVETENSKAP -- Fysik (hsv//swe)
- NATURAL SCIENCES -- Physical Sciences (hsv//eng)
Keyword
- Hepatocellular carcinoma
- Redox metabolism
- Systems biology
- Precision medicine
- Cancer
- gene-expression
- oxidative stress
- class discovery
- poor-prognosis
- genome-scale
- cancer
- survival
- progression
- metabolism
- prediction
- General & Internal Medicine
- Research & Experimental Medicine
- Systems biology
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Benfeitas, Rui
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Bidkhori, Gholam ...
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Mukhopadhyay, B.
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Klevstig, Martin ...
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Arif, Muhammad
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Zhang, C.
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show more...
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Lee, Sunjae
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Cinar, R.
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Nielsen, Jens B, ...
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Uhlén, Mathias
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Borén, Jan, 1963
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Kunos, G.
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Mardinoglu, Adil ...
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Medical Genetics
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Bioinformatics a ...
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Physical Science ...
- Articles in the publication
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Ebiomedicine
- By the university
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University of Gothenburg
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Chalmers University of Technology
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Royal Institute of Technology