title: Dysregulated signaling hubs of liver lipid metabolism reveal hepatocellular carcinoma pathogenesis.
abstract: Hepatocellular carcinoma (HCC) has a high mortality rate and early detection of HCC is crucial for the application of effective treatment strategies. HCC is typically caused by either viral hepatitis infection or by fatty liver disease. To diagnose and treat HCC it is necessary to elucidate the underlying molecular mechanisms. As a major cause for development of HCC is fatty liver disease, we here investigated anomalies in regulation of lipid metabolism in the liver. We applied a tailored network-based approach to identify signaling hubs associated with regulation of this part of metabolism. Using transcriptomics data of HCC patients, we identified significant dysregulated expressions of lipid-regulated genes, across many different lipid metabolic pathways. Our findings, however, show that viral hepatitis causes HCC by a distinct mechanism, less likely involving lipid anomalies. Based on our analysis we suggest signaling hub genes governing overall catabolic or anabolic pathways, as novel drug targets for treatment of HCC that involves lipid anomalies.
authors.affiliation: Science for Life Laboratory, KTH - Royal Institute of Technology, Stockholm, SE-171 21, Sweden Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology, Daejeon 305 338, Republic of Korea.
authors.forename: Sunjae
authors.initials: S
authors.lastname: Lee
authors.affiliation: Science for Life Laboratory, KTH - Royal Institute of Technology, Stockholm, SE-171 21, Sweden Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, SE-412 96, Sweden.
authors.forename: Adil
authors.initials: A
authors.lastname: Mardinoglu
authors.affiliation: Science for Life Laboratory, KTH - Royal Institute of Technology, Stockholm, SE-171 21, Sweden.
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology, Daejeon 305 338, Republic of Korea.
authors.forename: Doheon
authors.initials: D
authors.lastname: Lee
authors.affiliation: Science for Life Laboratory, KTH - Royal Institute of Technology, Stockholm, SE-171 21, Sweden Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, SE-412 96, Sweden nielsenj@chalmers.se.
authors.forename: Jens
authors.initials: J
authors.lastname: Nielsen
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D050356:Lipid Metabolism / Q000235:genetics*; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D053858:Metabolic Networks and Pathways / Q000235:genetics*; D059467:Transcriptome / Q000235:genetics