Ulrick Espelund1, Henning Grønbæk2, Gerda Elisabeth Villadsen2, Kira Simonsen2, Poul Frølund Vestergaard3, Jens Otto Lunde Jørgensen3, Allan Flyvbjerg1, Hendrik Vilstrup2, Jan Frystyk4. 1. Medical Research Laboratory, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark; Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark. 2. Department of Hepatology & Gastroenterology, Aarhus University Hospital and Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. 3. Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark. 4. Medical Research Laboratory, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark; Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark. Electronic address: frystyk@clin.au.dk.
Abstract
BACKGROUND: Previous studies have demonstrated an elevated IGF-II mRNA expression and protein levels in tumors and blood from patients with hepatocellular carcinoma (HCC), hereby suggesting a role of IGF-II as a pathogenic marker of HCC. We hypothesized that in HCC, an increased IGF-II secretion would translate into an elevated circulating IGF bioactivity, which would normalize following treatment. METHODS: Patients with HCC (n=39) were studied before and after radio-frequency ablation and/or transarterial chemo-embolization. Baseline data were compared to healthy subjects (n=150) and patients with liver cirrhosis (n=41). Serum levels of IGF ligands and IGF binding proteins (IGFBPs) were determined using gold standard methods as well as novel assays and compared to liver function tests and HCC treatment status. RESULTS: At baseline, HCC patients differed from cirrhosis patients and healthy controls regarding IGF-I (29 [23-37] vs. 12 [7-19] vs. 109 [103-116] μg/l), IGF-II (254 [224-288] vs. 118 [102-137] vs. 545 [525-566] μg/l) and IGF bioactivity (0.53 [0.41-0.68] vs. 0.29 [0.24-0.34] vs. 1.43 [1.33-1.53] μg/l) (mean [95% confidence interval], all age-adjusted P<0.001). All variables but IGFBP-2 were strongly associated with liver status (MELD score), and accordingly, differences were either attenuated or disappeared when adjusted for MELD score. There was no effect of treatment on any IGF variables. CONCLUSIONS: The marked differences in IGF and IGFBP levels between patients with HCC, liver cirrhosis and healthy subjects are mainly explained by variations in liver status. Therefore, this study questions the clinical utility of circulating IGF variables as markers of HCC.
BACKGROUND: Previous studies have demonstrated an elevated IGF-II mRNA expression and protein levels in tumors and blood from patients with hepatocellular carcinoma (HCC), hereby suggesting a role of IGF-II as a pathogenic marker of HCC. We hypothesized that in HCC, an increased IGF-II secretion would translate into an elevated circulating IGF bioactivity, which would normalize following treatment. METHODS:Patients with HCC (n=39) were studied before and after radio-frequency ablation and/or transarterial chemo-embolization. Baseline data were compared to healthy subjects (n=150) and patients with liver cirrhosis (n=41). Serum levels of IGF ligands and IGF binding proteins (IGFBPs) were determined using gold standard methods as well as novel assays and compared to liver function tests and HCC treatment status. RESULTS: At baseline, HCC patients differed from cirrhosispatients and healthy controls regarding IGF-I (29 [23-37] vs. 12 [7-19] vs. 109 [103-116] μg/l), IGF-II (254 [224-288] vs. 118 [102-137] vs. 545 [525-566] μg/l) and IGF bioactivity (0.53 [0.41-0.68] vs. 0.29 [0.24-0.34] vs. 1.43 [1.33-1.53] μg/l) (mean [95% confidence interval], all age-adjusted P<0.001). All variables but IGFBP-2 were strongly associated with liver status (MELD score), and accordingly, differences were either attenuated or disappeared when adjusted for MELD score. There was no effect of treatment on any IGF variables. CONCLUSIONS: The marked differences in IGF and IGFBP levels between patients with HCC, liver cirrhosis and healthy subjects are mainly explained by variations in liver status. Therefore, this study questions the clinical utility of circulating IGF variables as markers of HCC.
Authors: Marchien G Dallinga; Yasmin I Habani; Richelle P Kayser; Cornelis J F Van Noorden; Ingeborg Klaassen; Reinier O Schlingemann Journal: Mol Biol Rep Date: 2020-03-04 Impact factor: 2.316
Authors: Ulrick Espelund; Andrew G Renehan; Søren Cold; Claus Oxvig; Lee Lancashire; Zhenqiang Su; Allan Flyvbjerg; Jan Frystyk Journal: Cancer Med Date: 2018-05-03 Impact factor: 4.452