Serum IGFBP-3 is a more effective predictor than IGF-1 and IGF-2 for the development of hepatocellular carcinoma in patients with chronic HCV infection

Abstract

Abstract. Hepatocellular carcinoma (HCC) contributes to 14.8% of all cancer mortality in Egypt, which has a high prevalence of hepatitis C virus (HCV). We have previously shown alterations in the insulin-like growth factor-1 (IGF-1) receptor signalling pathway during experimental hepatocarcinogenesis. The aim of this study was to determine whether serum levels of IGF-1, IGF-2 and IGFBP-3 can be used to discriminate between HCC and the stages of hepatic dysfunction in patients with liver cirrhosis assessed by the Child-Pugh (CP) score, and to correlate these levels with HCC stages. We recruited 241 subjects to the present study; 79 with liver cirrhosis, 62 with HCV-induced HCC and 100 age-matched controls. Results showed that serum levels of IGF-1, IGF-2 and IGFBP-3 were reduced significantly in cirrhosis and HCC patients in comparison to the controls, and that this reduction negatively correlated with the CP scores. However, only IGFBP-3 levels showed significant negative correlation with α-fetoprotein levels. The reduction in IGF-1 and IGFBP-3 but not IGF-2 levels was significant in HCC in comparison to patients with cirrhosis. None of the parameters significantly correlated with the HCC stage. IGFBP-3 levels discriminated between cirrhosis and HCC at a sensitivity of 87%, a specificity of 80% and a cut-off value of <682.6 ng/ ml. In conclusion, although our results showed that serum IGF-1, IGF-2 and IGFBP-3 are reduced with the progression of hepatic dysfunction, only IGFBP-3 may be considered as the most promising serological marker for the prediction of the development of HCC in the chronic HCV patients with liver cirrhosis.

Evaluation of Taline-1, MCP-1 and IGF-1 in Prediction the Risk of Developing Hepatocellular Carcinoma in Patients With Liver Cirrhosis

“…the obtained data were near those obtaind by Su et al, [26] who demonstrate that the development of HCC is accompanied by a significant reduction of serum IGF-I levels in comparison to healthy subjects which is also noted in chronic liver disease. To the opposite of our results, Aleem et al, [3] reported that the reduction of IGF-1 levels was statistically significant between cirrhosis and HCC patients. As regarding the decrease in IGF-1 in cirrhotic patients than healthy subjects many studies contribute this decrease to affection of liver parenchyma that reduce synthetic capability of damaged hepatocytes because hepatocytes are the main contributors of circulating IGF.The present study showed that there were significant positive correlations between IGF-1 level and total protein, albumin and MCP-1.…”

“…Most imaging techniques help to discover HCC after considerable time of onset of tumor. In most instances, oncologists depend on AFP as the commonest and feasible marker for assessing HCC in addition to imaging (3). However, AFP is not completely a reliable marker in early HCC diagnosis, prevention or therapy due to its low specificity and sensitivity.…”

Immunohistochemical Distinction of Hepatocellular Carcinoma Using Arginase-1, Hepatocyte Paraffin Antigen -1 and Glypican-3

“…Egypt has a high prevalence of HCC; it is the second most cancer site among males after cancer bladder and seventh among females [2] . Such high incidence has been attributed to the high prevalence of hepatitis C virus (HCV) amongst Egyptians [3] .Based on histological characters, most HCCs can be easily identified on hematoxylin and eosin stained sections. However, some types of benign and malignant tumors may share the morphologic features.…”

“…Egypt has a high prevalence of HCC; it is the second most cancer site among males after cancer bladder and seventh among females [2] . Such high incidence has been attributed to the high prevalence of hepatitis C virus (HCV) amongst Egyptians [3] .…”

“…There is a limited number of ancillary immunohistochemical biomarkers used for distinguishing HCC from adenocarcinoma including HepPar-1, polyclonal carcinoembryonic antigen (CEA), and cluster of differentiation 10 (CD10), with Alfa-fetoprotein (AFP) and GPC-3 [3] . However, the suboptimal sensitivity and difficulty in interpretation of each one of such biomarkers renders its utility to be limited [7] .…”