title: Longitudinal metabolic imaging of hepatocellular carcinoma in transgenic mouse models identifies acylcarnitine as a potential biomarker for early detection.
abstract: The cumulative effects of hepatic injury due to hepatitis B virus (HBV) infections and aflatoxin-B1 (AFB1) exposure are the major risk factors of HCC. Understanding early metabolic changes involving these risk factors in an animal model closely resembling human hepatocellular carcinoma (HCC) is critical for biomarker discovery and disease therapeutics. We have used the hepatitis B surface antigen (HBsAg) transgenic mouse model that mimics HBV carriers with and without AFB1 treatment. We investigated early metabolic changes from preneoplastic state to HCC by non-invasive longitudinal imaging in three HCC groups of mice: HBsAg + AFB1(Gp-I), AFB1 alone (Gp-II), HBsAg alone (Gp-III) and a control group (wild-type untreated; Gp-IV). For the first time, we have identified acylcarnitine signals in vivo in the liver prior to the histological manifestation of the tumors in all three groups. Acylcarnitine concentration increased with increase in tumor growth in all HCC mouse models, indicating elevated metabolic activity and increased cell turnover. This was confirmed in a pilot study using human serum from HCC patients, which revealed a higher concentration of acylcarnitine compared with normal subjects. Translational clinical studies can be designed to detect acylcarnitine in patients with high risk factors for HCC.
authors.affiliation: Laboratory of Molecular Imaging, Singapore Bioimaging Consortium, Agency for Science, Technology and Research, Singapore.
authors.forename: Jadegoud
authors.initials: J
authors.lastname: Yaligar
authors.affiliation: Laboratory of Molecular Carcinogenesis, National Cancer Center, Singapore.
authors.forename: Wei Wei
authors.initials: WW
authors.lastname: Teoh
authors.affiliation: Laboratory of Molecular Carcinogenesis, National Cancer Center, Singapore.
authors.forename: Rashidah
authors.initials: R
authors.lastname: Othman
authors.affiliation: Laboratory of Molecular Imaging, Singapore Bioimaging Consortium, Agency for Science, Technology and Research, Singapore.
authors.forename: Sanjay Kumar
authors.initials: SK
authors.lastname: Verma
authors.affiliation: Laboratory of Molecular Carcinogenesis, National Cancer Center, Singapore.
authors.forename: Beng Hooi
authors.initials: BH
authors.lastname: Phang
authors.affiliation: Laboratory of Molecular Imaging, Singapore Bioimaging Consortium, Agency for Science, Technology and Research, Singapore.
authors.forename: Swee Shean
authors.initials: SS
authors.lastname: Lee
authors.affiliation: Laboratory of Cell Therapy and cancer Vaccine, National Cancer Center, Singapore.
authors.forename: Who Whong
authors.initials: WW
authors.lastname: Wang
authors.affiliation: Laboratory of Cell Therapy and cancer Vaccine, National Cancer Center, Singapore.
authors.forename: Han Chong
authors.initials: HC
authors.lastname: Toh
authors.affiliation: Laboratory of Molecular Imaging, Singapore Bioimaging Consortium, Agency for Science, Technology and Research, Singapore.
authors.forename: Venkatesh
authors.initials: V
authors.lastname: Gopalan
authors.affiliation: Laboratory of Molecular Carcinogenesis, National Cancer Center, Singapore.
authors.forename: Kanaga
authors.initials: K
authors.lastname: Sabapathy
authors.affiliation: Laboratory of Molecular Imaging, Singapore Bioimaging Consortium, Agency for Science, Technology and Research, Singapore.
authors.forename: S Sendhil
authors.initials: SS
authors.lastname: Velan
mesh_terms: D000818:Animals; D015415:Biomarkers; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism*; D002331:Carnitine / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism; D038524:Diffusion Magnetic Resonance Imaging; D004195:Disease Models, Animal; D055088:Early Detection of Cancer; D020869:Gene Expression Profiling; D006801:Humans; D008113:Liver Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D057054:Molecular Imaging / Q000379:methods; D047368:Tumor Burden
chemical_list: D015415:Biomarkers; C116917:acylcarnitine; D002331:Carnitine
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