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Serum levels of chemokines CCL4 and CCL5 in cirrhotic patients indicate the presence of hepatocellular carcinoma

View Article: PubMed Central - PubMed

ABSTRACT

Background:: Most hepatocellular carcinomas (HCCs) are diagnosed at an advanced stage. The prognostic value of serum tumour markers alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) is limited. The aim of our study is to evaluate the diagnostic value of serum growth factors, apoptotic and inflammatory mediators of cirrhotic patients with and without HCC.

Methods:: Serum samples were collected from cirrhotic potential liver transplant patients (LTx) with (n=61) and without HCC (n=78) as well as from healthy controls (HCs; n=39). Serum concentrations of CRP, neopterin and IL-6 as markers of inflammation and thrombopoietin (TPO), GCSF, FGF basic and VEGF, HMGB1, CK-18 (M65) and CK18 fragment (M30) and a panel of proinflammatory chemokines (CCL2, CCL3, CCL4, CCL5, CXCL5 and IL-8) were measured. Chi square, Fisher exact, Mann–Whitney U-tests, ROC curve analysis and forward stepwise logistic regression analyses were applied.

Results:: Patients with HCC had higher serum TPO and chemokines (P<0.001 for TPO, CCL4, CCL5 and CXCL5) and lower CCL2 (P=0.008) levels than cirrhotic patients without HCC. Multivariate forward stepwise regression analysis for significant parameters showed that among the studied parameters CCL4 and CCL5 (P=0.001) are diagnostic markers of HCC. Serum levels of TPO and chemokines were lower, whereas M30 was significantly higher in cirrhotic patients than in HCs.

Conclusions:: High serum levels of inflammatory chemokines such as CCL4 and CCL5 in the serum of cirrhotic patients indicate the presence of HCC.

No MeSH data available.


Algorithmic approach to AFP, CCL4 and CCL5 tests in cirrhotic patients.
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fig3: Algorithmic approach to AFP, CCL4 and CCL5 tests in cirrhotic patients.

Mentions: To our knowledge, the association of HCC with CCL4 gene expression and/or serum levels was not studied so far. Thus our report is the first study that evaluates this association. CCL4 and CCL5 can bind to their receptors in the carcinomatous tissues and Kupffer cells in the liver and induce the infiltration of various inflammatory cells. We speculate that cirrhotic high producers of CCL4 and CCL5 are at higher risk of HCC. It can be postulated that high serum levels of CCL4 and CCL5 indicate the presence of HCC in patients with liver cirrhosis and along with other indicators can help in early detection of HCC. Algorithmic approach of our results (Figure 3) indicates that AFP is a specific test in patients with suspected HCC (imaging). When imaging is positive but AFP is negative, surrogate markers such CCL5 and CCL4 are confirmatory tests. We recommend a liver biopsy in patients with positive imaging and negative AFP, when CCL5 and/or CCL4 are positive.


Serum levels of chemokines CCL4 and CCL5 in cirrhotic patients indicate the presence of hepatocellular carcinoma
Algorithmic approach to AFP, CCL4 and CCL5 tests in cirrhotic patients.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4559820&req=5

fig3: Algorithmic approach to AFP, CCL4 and CCL5 tests in cirrhotic patients.
Mentions: To our knowledge, the association of HCC with CCL4 gene expression and/or serum levels was not studied so far. Thus our report is the first study that evaluates this association. CCL4 and CCL5 can bind to their receptors in the carcinomatous tissues and Kupffer cells in the liver and induce the infiltration of various inflammatory cells. We speculate that cirrhotic high producers of CCL4 and CCL5 are at higher risk of HCC. It can be postulated that high serum levels of CCL4 and CCL5 indicate the presence of HCC in patients with liver cirrhosis and along with other indicators can help in early detection of HCC. Algorithmic approach of our results (Figure 3) indicates that AFP is a specific test in patients with suspected HCC (imaging). When imaging is positive but AFP is negative, surrogate markers such CCL5 and CCL4 are confirmatory tests. We recommend a liver biopsy in patients with positive imaging and negative AFP, when CCL5 and/or CCL4 are positive.

View Article: PubMed Central - PubMed

ABSTRACT

Background:: Most hepatocellular carcinomas (HCCs) are diagnosed at an advanced stage. The prognostic value of serum tumour markers alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) is limited. The aim of our study is to evaluate the diagnostic value of serum growth factors, apoptotic and inflammatory mediators of cirrhotic patients with and without HCC.

Methods:: Serum samples were collected from cirrhotic potential liver transplant patients (LTx) with (n=61) and without HCC (n=78) as well as from healthy controls (HCs; n=39). Serum concentrations of CRP, neopterin and IL-6 as markers of inflammation and thrombopoietin (TPO), GCSF, FGF basic and VEGF, HMGB1, CK-18 (M65) and CK18 fragment (M30) and a panel of proinflammatory chemokines (CCL2, CCL3, CCL4, CCL5, CXCL5 and IL-8) were measured. Chi square, Fisher exact, Mann–Whitney U-tests, ROC curve analysis and forward stepwise logistic regression analyses were applied.

Results:: Patients with HCC had higher serum TPO and chemokines (P<0.001 for TPO, CCL4, CCL5 and CXCL5) and lower CCL2 (P=0.008) levels than cirrhotic patients without HCC. Multivariate forward stepwise regression analysis for significant parameters showed that among the studied parameters CCL4 and CCL5 (P=0.001) are diagnostic markers of HCC. Serum levels of TPO and chemokines were lower, whereas M30 was significantly higher in cirrhotic patients than in HCs.

Conclusions:: High serum levels of inflammatory chemokines such as CCL4 and CCL5 in the serum of cirrhotic patients indicate the presence of HCC.

No MeSH data available.