Abstract
Understanding the dynamics of the complex interaction network of cytokines, defined as ‘‘cytokinome’’, can be useful to follow progression and evolution of hepatocellular carcinoma (HCC) from its early stages as well as to define therapeutic strategies. Recently we have evaluated the cytokinome profile in patients with type 2 diabetes (T2D) and/or chronic hepatitis C (CHC) infection and/or cirrhosis suggesting specific markers for the different stages of the diseases. Since T2D has been identified as one of the contributory cause of HCC, in this paper we examined the serum levels of cytokines, growth factors, chemokines, as well as of other cancer and diabetes biomarkers in a discovery cohort of patients with T2D, chronic hepatitis C (CHC) and/or CHC-related HCC comparing them with a healthy control group to define a profile of proteins able to characterize these patients, and to recognize the association between diabetes and HCC. The results have evidenced that the serum levels of some proteins are significantly and differently up-regulated in all the patients but they increased still more when HCC develops on the background of T2D. Our results were verified also using a separate validation cohort. Furthermore, significant correlations between clinical and laboratory data characterizing the various stages of this complex disease, have been found. In overall, our results highlighted that a large and simple omics approach, such as that of the cytokinome analysis, supplemented by common biochemical and clinical data, can give a complete picture able to improve the prognosis of the various stages of the disease progression. We have also demonstrated by means of interactomic analysis that our experimental results correlate positively with the general metabolic picture that is emerging in the literature for this complex multifactorial disease.
Highlights
It has been reported that the liver cancer is the second death cause due to cancer
Several risk factors have been identified to contribute to the international burden of hepatocellular carcinoma (HCC) such as chronic infection with hepatitis B virus (HBV) and hepatitis C virus (HCV), alcoholic liver disease, non-alcoholic steato-hepatitis (NASH), diabetes mellitus (DM), obesity, intake of aflatoxins-contaminated food, tobacco smoking, excessive alcohol drinking and genetically inherited disorders [2]
The type 2 diabetes (T2D) is a metabolic disorder characterized by hyperglycemia which may predispose the liver to relative insulin resistance due to inadequate secretion or receptor insensitivity to the endogenous insulin
Summary
It has been reported that the liver cancer is the second death cause due to cancer. Several risk factors have been identified to contribute to the international burden of HCC such as chronic infection with hepatitis B virus (HBV) and hepatitis C virus (HCV), alcoholic liver disease, non-alcoholic steato-hepatitis (NASH), diabetes mellitus (DM), obesity, intake of aflatoxins-contaminated food, tobacco smoking, excessive alcohol drinking and genetically inherited disorders (hemochromatosis, α1 anti-trypsin deficiency, porphyrias) [2]. Type 2 diabetes has been associated with increase risk for several malignancies including breast, colon, kidney, liver, endometrium and pancreatic cancers [3]. T2D as part of the insulin resistance syndrome, has been implicated as a risk factor for non-alcoholic fatty liver disease (NAFLD), including its most severe form non-alcoholic steato-hepatitis (NASH), and has been identified as a cause of both cirrhosis and HCC [6]
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