Serum Biomarkers for Early Detection of Hepatocellular Carcinoma Associated with HCV Infection in Egyptian Patients

Abstract

Background: Early detection of hepatocellular carcinoma using serological markers with better sensitivity and specificity than alpha fetoprotein (AFP) is needed. Aims: The aim of this study was to evaluate the diagnostic value of serum sICAM-1, β-catenin, IL-8, proteasome and sTNFR-II in early detection of HCC. Materials and Methods: Serum levels of IL-8, sICAM-1, sTNFR-II, proteasome and β-catenin were measured by ELISA assay in 479 serum samples from 192 patients with HCC, 96 patients with liver cirrhosis (LC), 96 patients with chronic hepatitis C (CHC) and 95 healthy controls. Results: Serum levels of proteasome, sICAM-1, β-catenin and αFP were significantly elevated in HCC group compared to other groups (P-value<0.001), where serum level of IL-8 was significantly elevated in the LC and HCC groups compared to CHC and control groups (P-value <0.001), while no significant difference was noticed in patients with HCC and LC (P-value=0.09). Serum level of sTNFR-II was significantly elevated in patients with LC compared to HCC, CHC and control groups (P-value <0.001); also it was significantly higher in HCC compared to CHC and control groups (P-value <0.001). ROC curve analysis of the studied markers between HCC and other groups revealed that the serum level of proteasome had sensitivity of 75.9% and specificity of 73.4% at a cut-off value of 0.32 μg/ml with AUC 0.803 sICAM-1 at cut off value of 778ng/ml, the sensitivity was 75.8% and the specificity was 71.8% with AUC 0.776. β-catenin had sensitivity and specificity of 70% and 68.6% respectively at a cut off value of 8.75ng/ml with an AUC of 0.729. sTNFR-II showed sensitivity of 86.3% and specificity of 51.8% at a cut off value of 6239.5pg/ml with an AUC of 0.722. IL-8 had sensitivity of 70.4% and specificity of 52.3% at a cut off value of 51.5pg/ml with AUC 0.631. Conclusions: Our data supported the role of proteasome, sICAM-1, sTNFR-II and β-catenin in early detection of HCC. Also, using this panel of serological markers in combination with αFP may offer improved diagnostic performance over αFP alone in the early detection of HCC.

Role of relevant immune-modulators and cytokines in hepatocellular carcinoma and premalignant hepatic lesions

“…It has been demonstrated as a monotherapy, and was approved for metastatic renal cell carcinoma and metastatic melanoma by the FDA[ 37 ]. Our results showed a significant increase in TNF-αR2 ( P < 0.001) and significant decrease in IL-2 ( P < 0.001) in HCC patients in relation to other groups, consistent with our previous results[ 38 , 39 ] that concluded the possible use of serum TNFR-II, IL-2Ra and IL-8 as combined biomarkers in HCV-infected patients at high risk of developing HCC.…”

Evaluation of trail receptor 1 (DR4) polymorphisms C626G and A683C as risk factors of hepatocellular carcinoma

“…The present study was performed on 80 HCC cases associated with HCV infection and in 80 subjects with HCV related liver cirrhosis, in order to verify the impact of these gene variants with the risk of tumor development. In the present study, HCC patients were older than cirrhotic patients that was in agreement with other studies and showed 3.4 folds increase in male incidence in agreement with . It was attributed to higher males exposure to risk factors for example, HBV, HCV, alcohol consumption, smoke cigarettes, and have increased iron stores in addition to the possible effect of androgens …”

“…HCC represents the second cause of cancer‐related mortality in the world . The burden of HCC has increased in Egypt with doubling the incidence in the past 10 years, certainly with aging . In addition, it showed a strong male predominance .…”

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

“…The serum alpha-fetoprotein (AFP) is the most commonly used HCC biomarker, However, its poor sensitivity and specificity renders it unsatisfactory for this purpose.The prognosis of HCC is very difficult which necessitates finding of new appropriate either single or panel serum markers that could be used for early detection of HCC in high risk patients like patients with liver cirrhosis (13) Taline-1 is a large cytoskeletal dimeric adaptor protein that associates with the integrin family of cell adhesion molecules in cell extracellular matrix junctions where it both activates integrins and couples them to the actin cytoskeleton (14) The current study showed high significant increases in the serum level of talin-1 in HCC patients in comparison with both cirrhotic and control groups. Also, there was a high significant increase in cirrhotic patients compared with the controls.…”