BACKGROUND & AIMS: Gene expression profiling of hepatocellular carcinoma (HCC) and background liver has been studied extensively; however, the relationship between the gene expression profiles of different lesions has not been assessed. METHODS: We examined the expression profiles of 34 HCC specimens (17 hepatitis B virus [HBV]-related and 17 hepatitis C virus [HCV]-related) and 71 non-tumor liver specimens (36 chronic hepatitis B [CH-B] and 35 chronic hepatitis C [CH-C]) using an in-house cDNA microarray consisting of liver-predominant genes. Graphical Gaussian modeling (GGM) was applied to elucidate the interactions of gene clusters among the HCC and non-tumor lesions. RESULTS: In CH-B-related HCC, the expression of vascular endothelial growth factor-family signaling and regulation of T cell differentiation, apoptosis, and survival, as well as development-related genes was up-regulated. In CH-C-related HCC, the expression of ectodermal development and cell proliferation, wnt receptor signaling, cell adhesion, and defense response genes was also up-regulated. Many of the metabolism-related genes were down-regulated in both CH-B- and CH-C-related HCC. GGM analysis of the HCC and non-tumor lesions revealed that DNA damage response genes were associated with AP1 signaling in non-tumor lesions, which mediates the expression of many genes in CH-B-related HCC. In contrast, signal transducer and activator of transcription 1 and phosphatase and tensin homolog were associated with early growth response protein 1 signaling in non-tumor lesions, which potentially promotes angiogenesis, fibrogenesis, and tumorigenesis in CH-C-related HCC. CONCLUSIONS: Gene expression profiling of HCC and non-tumor lesions revealed the predisposing changes of gene expression in HCC. This approach has potential for the early diagnosis and possible prevention of HCC.
BACKGROUND & AIMS: Gene expression profiling of hepatocellular carcinoma (HCC) and background liver has been studied extensively; however, the relationship between the gene expression profiles of different lesions has not been assessed. METHODS: We examined the expression profiles of 34 HCC specimens (17 hepatitis B virus [HBV]-related and 17 hepatitis C virus [HCV]-related) and 71 non-tumor liver specimens (36 chronic hepatitis B [CH-B] and 35 chronic hepatitis C [CH-C]) using an in-house cDNA microarray consisting of liver-predominant genes. Graphical Gaussian modeling (GGM) was applied to elucidate the interactions of gene clusters among the HCC and non-tumor lesions. RESULTS: In CH-B-related HCC, the expression of vascular endothelial growth factor-family signaling and regulation of T cell differentiation, apoptosis, and survival, as well as development-related genes was up-regulated. In CH-C-related HCC, the expression of ectodermal development and cell proliferation, wnt receptor signaling, cell adhesion, and defense response genes was also up-regulated. Many of the metabolism-related genes were down-regulated in both CH-B- and CH-C-related HCC. GGM analysis of the HCC and non-tumor lesions revealed that DNA damage response genes were associated with AP1 signaling in non-tumor lesions, which mediates the expression of many genes in CH-B-related HCC. In contrast, signal transducer and activator of transcription 1 and phosphatase and tensin homolog were associated with early growth response protein 1 signaling in non-tumor lesions, which potentially promotes angiogenesis, fibrogenesis, and tumorigenesis in CH-C-related HCC. CONCLUSIONS: Gene expression profiling of HCC and non-tumor lesions revealed the predisposing changes of gene expression in HCC. This approach has potential for the early diagnosis and possible prevention of HCC.
Authors: Giacomo Diaz; Ronald E Engle; Ashley Tice; Marta Melis; Stephanie Montenegro; Jaime Rodriguez-Canales; Jeffrey Hanson; Michael R Emmert-Buck; Kevin W Bock; Ian N Moore; Fausto Zamboni; Sugantha Govindarajan; David E Kleiner; Patrizia Farci Journal: Mol Cancer Res Date: 2018-06-01 Impact factor: 5.852