Characterization of heterogeneous redox responses in hepatocellular carcinoma patients using network analysis
Artikel i vetenskaplig tidskrift, 2019
© 2019 The Authors 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.
Systems biology
Precision medicine
Hepatocellular carcinoma
Redox metabolism
Liver cancer
Cancer
Transcriptomics
Författare
Rui Benfeitas
Kungliga Tekniska Högskolan (KTH)
G. Bidkhori
Kungliga Tekniska Högskolan (KTH)
B. Mukhopadhyay
National Institute on Alcohol Abuse and Alcoholism
M. Klevstig
Sahlgrenska universitetssjukhuset
Muhammad Arif
Kungliga Tekniska Högskolan (KTH)
C. Zhang
Kungliga Tekniska Högskolan (KTH)
Sunjae Lee
Kungliga Tekniska Högskolan (KTH)
R. Cinar
National Institute on Alcohol Abuse and Alcoholism
Jens B Nielsen
Chalmers, Biologi och bioteknik, Systembiologi
Mathias Uhlen
Kungliga Tekniska Högskolan (KTH)
Jan Borén
Sahlgrenska universitetssjukhuset
G. Kunos
National Institute on Alcohol Abuse and Alcoholism
Adil Mardinoglu
Kungliga Tekniska Högskolan (KTH)
Chalmers, Biologi och bioteknik, Systembiologi
King's College London
EBioMedicine
2352-3964 (eISSN)
Vol. 40 471-487Ämneskategorier
Medicinsk genetik
Bioinformatik och systembiologi
Cancer och onkologi
DOI
10.1016/j.ebiom.2018.12.057
PubMed
30606699