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The Cytokinome Profile in Patients with Hepatocellular Carcinoma and Type 2 Diabetes.

Capone F, Guerriero E, Colonna G, Maio P, Mangia A, Marfella R, Paolisso G, Izzo F, Potenza N, Tomeo L, Castello G, Costantini S - PLoS ONE (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: CROM, Istituto Nazionale Tumori "Fondazione G. Pascale"-IRCCS, Naples, Italy.

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.

No MeSH data available.


Related in: MedlinePlus

Significant cytokines in some patient groups belonging to discovery set.We report the significant molecule levels from controls, patients with type 2 diabetes (T2D), chronic hepatitis C (CHC), hepatocellular carcinoma (HCC) and hepatocellular carcinoma and type 2 diabetes (T2D-HCC) shown by means of box-and-whisker graphs. The boxes extend from the 25th to the 75th percentile, and the line in the middle is the median. The error bars extend down to the lowest value and up to the highest.
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pone.0134594.g001: Significant cytokines in some patient groups belonging to discovery set.We report the significant molecule levels from controls, patients with type 2 diabetes (T2D), chronic hepatitis C (CHC), hepatocellular carcinoma (HCC) and hepatocellular carcinoma and type 2 diabetes (T2D-HCC) shown by means of box-and-whisker graphs. The boxes extend from the 25th to the 75th percentile, and the line in the middle is the median. The error bars extend down to the lowest value and up to the highest.

Mentions: In Fig 1, and in Tables 2 and 3 we report the proteins that show different serum levels in T2D or CHC or HCC patients respect to controls with the related statistical evaluations; data not statistically significant are not reported. Greater amounts of HGF, IL-2R, s-IL-6Ra, IL-18, leptin, sVEGFR-1 and sVEGFR-2 were secreted by T2D, CHC and HCC patients in comparison with the healthy controls, whereas those of glucagon only by T2D and HCC patients, those of β-NGF, CXCL1, CXCL9, CXCL12, IL-16, and PECAM-1 by CHC and HCC patients, and those of IFN-α and Prolactin only in HCC patients. The most part of these data agrees with our recently published results. In fact, we have confirmed the increased amount of IL-2R, IL-18, HGF, glucagon, and leptin that were found in T2D patients [9] as well as of β-NGF, CXCL1, CXCL9, CXCL12, HGF, IL-2R, s-IL-6Ra, IL-18, IFN-α, IL-16, PECAM-1 and Prolactin found in patients with CHC as well as with HCC and CHC-related cirrhosis [8–9].


The Cytokinome Profile in Patients with Hepatocellular Carcinoma and Type 2 Diabetes.

Capone F, Guerriero E, Colonna G, Maio P, Mangia A, Marfella R, Paolisso G, Izzo F, Potenza N, Tomeo L, Castello G, Costantini S - PLoS ONE (2015)

Significant cytokines in some patient groups belonging to discovery set.We report the significant molecule levels from controls, patients with type 2 diabetes (T2D), chronic hepatitis C (CHC), hepatocellular carcinoma (HCC) and hepatocellular carcinoma and type 2 diabetes (T2D-HCC) shown by means of box-and-whisker graphs. The boxes extend from the 25th to the 75th percentile, and the line in the middle is the median. The error bars extend down to the lowest value and up to the highest.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4520685&req=5

pone.0134594.g001: Significant cytokines in some patient groups belonging to discovery set.We report the significant molecule levels from controls, patients with type 2 diabetes (T2D), chronic hepatitis C (CHC), hepatocellular carcinoma (HCC) and hepatocellular carcinoma and type 2 diabetes (T2D-HCC) shown by means of box-and-whisker graphs. The boxes extend from the 25th to the 75th percentile, and the line in the middle is the median. The error bars extend down to the lowest value and up to the highest.
Mentions: In Fig 1, and in Tables 2 and 3 we report the proteins that show different serum levels in T2D or CHC or HCC patients respect to controls with the related statistical evaluations; data not statistically significant are not reported. Greater amounts of HGF, IL-2R, s-IL-6Ra, IL-18, leptin, sVEGFR-1 and sVEGFR-2 were secreted by T2D, CHC and HCC patients in comparison with the healthy controls, whereas those of glucagon only by T2D and HCC patients, those of β-NGF, CXCL1, CXCL9, CXCL12, IL-16, and PECAM-1 by CHC and HCC patients, and those of IFN-α and Prolactin only in HCC patients. The most part of these data agrees with our recently published results. In fact, we have confirmed the increased amount of IL-2R, IL-18, HGF, glucagon, and leptin that were found in T2D patients [9] as well as of β-NGF, CXCL1, CXCL9, CXCL12, HGF, IL-2R, s-IL-6Ra, IL-18, IFN-α, IL-16, PECAM-1 and Prolactin found in patients with CHC as well as with HCC and CHC-related cirrhosis [8–9].

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: CROM, Istituto Nazionale Tumori "Fondazione G. Pascale"-IRCCS, Naples, Italy.

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.

No MeSH data available.


Related in: MedlinePlus