title: Integrative genomic signatures of hepatocellular carcinoma derived from nonalcoholic Fatty liver disease.
abstract: Nonalcoholic fatty liver disease (NAFLD) is a risk factor for Hepatocellular carcinoma (HCC), but he transition from NAFLD to HCC is poorly understood. Feature selection algorithms in human and genetically modified mice NAFLD and HCC microarray data were applied to generate signatures of NAFLD progression and HCC differential survival. These signatures were used to study the pathogenesis of NAFLD derived HCC and explore which subtypes of cancers that can be investigated using mouse models. Our findings show that: (I) HNF4 is a common potential transcription factor mediating the transcription of NAFLD progression genes (II) mice HCC derived from NAFLD co-cluster with a less aggressive human HCC subtype of differential prognosis and mixed etiology (III) the HCC survival signature is able to correctly classify 95% of the samples and gives Fgf20 and Tgfb1i1 as the most robust genes for prediction (IV) the expression values of genes composing the signature in an independent human HCC dataset revealed different HCC subtypes showing differences in survival time by a Logrank test. In summary, we present marker signatures for NAFLD derived HCC molecular pathogenesis both at the gene and pathway level.
authors.affiliation: Metabolomics Unit, CIC bioGUNE, Centro de Investigación Cooperativa en Biociencias, Bizkaia Technology Park, Derio, Bizkaia, Spain; Department of Plant Protection Biology, Swedish University of Agricultural Sciences, Alnarp, Sweden.
authors.forename: Itziar
authors.initials: I
authors.lastname: Frades
authors.affiliation: Department of Plant Protection Biology, Swedish University of Agricultural Sciences, Alnarp, Sweden.
authors.forename: Erik
authors.initials: E
authors.lastname: Andreasson
authors.affiliation: Metabolomics Unit, CIC bioGUNE, Centro de Investigación Cooperativa en Biociencias, Bizkaia Technology Park, Derio, Bizkaia, Spain.
authors.forename: Jose Maria
authors.initials: JM
authors.lastname: Mato
authors.affiliation: Department of Plant Protection Biology, Swedish University of Agricultural Sciences, Alnarp, Sweden.
authors.forename: Erik
authors.initials: E
authors.lastname: Alexandersson
authors.affiliation: Department of Human genetics, National Health Institute Doutor Ricardo Jorge, Lisboa, Portugal.
authors.forename: Rune
authors.initials: R
authors.lastname: Matthiesen
authors.affiliation: Metabolomics Unit, CIC bioGUNE, Centro de Investigación Cooperativa en Biociencias, Bizkaia Technology Park, Derio, Bizkaia, Spain.
authors.forename: Maria Luz
authors.initials: ML
authors.lastname: Martínez-Chantar
mesh_terms: D000818:Animals; D015415:Biomarkers; D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D018450:Disease Progression; D005346:Fibroblast Growth Factors / Q000235:genetics; D051557:Hepatocyte Nuclear Factor 4 / Q000235:genetics; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D060588:LIM Domain Proteins / Q000235:genetics; D008099:Liver / Q000473:pathology; D008113:Liver Neoplasms / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D065626:Non-alcoholic Fatty Liver Disease / Q000235:genetics* / Q000473:pathology; D012307:Risk Factors; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D015415:Biomarkers; C416003:FGF20 protein, human; C496592:HNF4A protein, human; D051557:Hepatocyte Nuclear Factor 4; D047908:Intracellular Signaling Peptides and Proteins; D060588:LIM Domain Proteins; C490351:TGFB1I1 protein, human; D005346:Fibroblast Growth Factors; D048051:p38 Mitogen-Activated Protein Kinases