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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.


CCL4 and CCL5 serum levels in cirrhotic patients with and without HCC as well as in healthy controls (HCs).
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fig1: CCL4 and CCL5 serum levels in cirrhotic patients with and without HCC as well as in healthy controls (HCs).

Mentions: HCC patients with cirrhosis were older, had more HCV+ and lower MELD score (11.8±5.0 vs 22.4±8.6: P<0.001), CRP (15.8±21.8 mg l−1vs 22.9±26.1: P=0.009) and neopterin (22.2±21.0 nmol l−1vs 58.1±76.8: P<0.001) than cirrhotic patients without HCC− (Table 1). AFP test was carried out in 102 cirrhotic patients; 23 of 49 HCC+ and 9 of 53 HCC− patients had positive results (P<0.0001). Serum levels of TPO (226±210 pg ml−1vs 163±247: P<0.001) and chemokines CCL4 (170±378 pg ml−1vs 101±483: P<0.0001), CCL5 (3.6±5.5 vs 2.0±4.5 ng ml−1: P<0.0001) and CXCL5 (230±301 vs 118±159 pg ml−1: P<0.001) were higher, whereas surprisingly CCL2 (129±192 pg ml−1 (median=80) vs 245±689 (median=111): P=0.008) was lower in HCC+ than in HCC− cirrhotic patients (Table 2 and Figure 1). Interestingly, the apoptosis marker M30 (P=0.60), M65 (P=0.92), GCSF (P=0.66), VEGF (P=0.51) and FGF basic (P=0.28) were similar in the two patient groups. The results indicate high expression of particular chemokines in HCC patients compared with cirrhotic patients without HCC.


Serum levels of chemokines CCL4 and CCL5 in cirrhotic patients indicate the presence of hepatocellular carcinoma
CCL4 and CCL5 serum levels in cirrhotic patients with and without HCC as well as in healthy controls (HCs).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig1: CCL4 and CCL5 serum levels in cirrhotic patients with and without HCC as well as in healthy controls (HCs).
Mentions: HCC patients with cirrhosis were older, had more HCV+ and lower MELD score (11.8±5.0 vs 22.4±8.6: P<0.001), CRP (15.8±21.8 mg l−1vs 22.9±26.1: P=0.009) and neopterin (22.2±21.0 nmol l−1vs 58.1±76.8: P<0.001) than cirrhotic patients without HCC− (Table 1). AFP test was carried out in 102 cirrhotic patients; 23 of 49 HCC+ and 9 of 53 HCC− patients had positive results (P<0.0001). Serum levels of TPO (226±210 pg ml−1vs 163±247: P<0.001) and chemokines CCL4 (170±378 pg ml−1vs 101±483: P<0.0001), CCL5 (3.6±5.5 vs 2.0±4.5 ng ml−1: P<0.0001) and CXCL5 (230±301 vs 118±159 pg ml−1: P<0.001) were higher, whereas surprisingly CCL2 (129±192 pg ml−1 (median=80) vs 245±689 (median=111): P=0.008) was lower in HCC+ than in HCC− cirrhotic patients (Table 2 and Figure 1). Interestingly, the apoptosis marker M30 (P=0.60), M65 (P=0.92), GCSF (P=0.66), VEGF (P=0.51) and FGF basic (P=0.28) were similar in the two patient groups. The results indicate high expression of particular chemokines in HCC patients compared with cirrhotic patients without HCC.

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&ndash;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&lt;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.