Distribution of insulin growth factor-1 (IGF-1) binding proteins in hepatocellular carcinoma with and without cirrhosis.

Abstract

193 Background: Circulating insulin-like growth factor-1 (IGF-1) significantly declines in patients (pts) with cirrhosis and hepatocellular carcinoma (HCC), reflecting damaged hepatocytes. The bioavailability of IGF-1 is controlled by insulin-like growth factor binding proteins (IGFBPs), which bind IGF-1. IGFBPs transcription is cell specific, and are secreted mainly by the liver. Variations in circulating IGFBPs in HCC pts, especially those with non-cirrhotic HCC, has not been elucidated. We investigated the expression of these proteins in HCC with and without cirrhosis. Methods: Under Institutional Review Board approval, we measured plasma levels of seven IGFBPs in 489 cirrhotic HCC pts, 274 non-cirrhotic HCC pts, 75 pts with cirrhosis without HCC, and 200 healthy controls. Also, we assessed variations in IGFBPs plasma level between early and advanced stage HCC in the presence and absence of cirrhosis. Levels of circulating biomarkers were summarized by descriptive statistics, and both Chi-square and ANOVA tests were used to compare levels between groups. Results: IGFBPs levels varied significantly between groups (Table). Moreover, IGFBP-3 was lower in HCC pts than in healthy controls ( P ≤ 0.001), and IGFBP-1, -2, -4, and -7 were higher in HCC without cirrhosis than in healthy controls ( P = 0.001 for all). Additionally, in non-cirrhotic HCC pts, a similar pattern was observed in advanced Stage HCC compared with early stage HCC. Conclusions: Levels of circulating IGFBPs may be associated with risk of non-cirrhotic HCC and could be used as markers for underlying liver damage. [Table: see text]