Expression levels of insulin-like growth factors and receptors in hepatocellular carcinoma: a retrospective study.

Yun Chun,Min Huang,Lori Rink,Margaret Von Mehren

doi:10.1186/1477-7819-12-231

Abstract

BackgroundThe insulin-like growth factor (IGF) pathway is implicated in the pathogenesis of hepatocellular carcinoma (HCC) and may be important in nonalcoholic fatty liver disease (NAFLD). The aim of this study is to determine expression levels of IGFs and receptors in NAFLD-associated HCC.MethodsTissue microarrays were constructed from patients who underwent hepatectomy for HCC. Immunohistochemistry was performed using antibodies for IGF ligands and receptors. Immunostain results were scored by a pathologist blinded to clinical data.ResultsAmong 27 patients with HCC, the most common underlying liver diseases included NAFLD, hepatitis C, and alcoholic hepatitis. Expression levels of IGFs and receptors were not associated with patients’ underlying liver disease. In all patients, IGF-2 expression was upregulated in tumor and adjacent non-neoplastic liver. Expression of IGF-1 was low in adjacent liver in 6 of 10 patients with cirrhosis, compared with 2 of 17 patients without cirrhosis (P = 0.025). Higher IGF-1 expression in liver adjacent to tumor was associated with poorer median survival of 22 months, compared with 72 months with equal or lower IGF-1 expression in adjacent liver relative to tumor (P = 0.006).ConclusionsOur preliminary results demonstrate significant associations between IGF-1 expression and liver cirrhosis and survival after resection in patients with HCC, independent of their underlying liver disease.

Highlights

The insulin-like growth factor (IGF) pathway is implicated in the pathogenesis of hepatocellular carcinoma (HCC) and may be important in nonalcoholic fatty liver disease (NAFLD)
Previous studies have demonstrated that the insulin-like growth factor (IGF) signal transduction pathway is activated early in up to 90% of HCC and may be important in patients with the metabolic syndrome and NAFLD [8]
IGF-1 receptor (IGF-1R) was strongly expressed in only one patient with alcoholic hepatitis

Summary

Introduction

The insulin-like growth factor (IGF) pathway is implicated in the pathogenesis of hepatocellular carcinoma (HCC) and may be important in nonalcoholic fatty liver disease (NAFLD). Nonalcoholic fatty liver disease (NAFLD) is increasingly recognized as a growing cause of nonalcoholic steatohepatitis, progressing to cirrhosis and HCC. Nonalcoholic fatty liver disease is the major hepatic manifestation of the metabolic syndrome, marked by obesity, The molecular basis for the transformation of NAFLD into HCC is poorly understood. Previous studies have demonstrated that the insulin-like growth factor (IGF) signal transduction pathway is activated early in up to 90% of HCC and may be important in patients with the metabolic syndrome and NAFLD [8]. Plasma levels of insulin-like growth factor-2 (IGF-2) are increased in obese and type 2 diabetic patients [10]. Signaling through the insulin and IGF-1 receptors has been shown to increase cellular proliferation, inhibit apoptosis, and promote metastasis

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