Serum Markers of Hepatocellular Carcinoma

Department of Biomedical Science, University of Catania, Via Androne 83, 95124, Catania, Italy.
Digestive Diseases and Sciences (Impact Factor: 2.55). 03/2010; 55(10):2744-55. DOI: 10.1007/s10620-010-1184-7
Source: PubMed

ABSTRACT The hepatocellular carcinoma is one of the most common malignant tumors and carries a poor survival rate. The management of patients at risk for developing HCC remains intricate.
A literature search identified potential markers for hepatocellular carcinoma. These markers were analysed and justification was provided for these factors' inclusion to (or exclusion from) the markers of hepatocellular carcinoma (HCC). A search of the literature was made using cancer literature and the PubMed database for the following keywords: "markers and HCC," "Lens culinaris agglutinin reactive AFP (AFP-L3) and HCC," "Des-γ-carboxy prothrombin (DCP) and HCC," "Glypican-3 and HCC," "Chromogranin A and HCC," "Transforming growth factor β1(TGF) and HCC," "α-l-fucosidase (AFU) and HCC," "Golgi protein-73 (GP73) and HCC," "Hepatocyte growth factor (HGF) and HCC," "Nervous growth factor (NGF) and HCC."
Despite the large number of studies devoted to the immunohistochemistry of HCC, at the present time, the absolute positive and negative markers for HCC are still lacking, and even those characterized by very high sensitivity and specificity do not have an universal diagnostic usefulness. Given the poor response to current therapies, a better understanding of the molecular pathways active in this disease could potentially provide new targets for therapy. However, AFP shows a low sensitivity, therefore other biomarkers have been developed to make an early diagnosis and improve patients' prognosis.

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    ABSTRACT: Tumor suppression of Transforming Growth Factor (TGF-β) signaling pathway requires an adaptor protein, Embryonic Liver Fodrin (ELF). Disruption of ELF expression resulted in miscolocalization of Smad3 and Smad4, then disruption of TGF-β signaling. However, the prognostic significance of ELF for hepatocellular carcinoma (HCC) hasn't been clarified. This study aimed to investigate whether measuring both TGF-β1 and ELF provides a more powerful predictor for HCC prognosis than either marker alone. TGF-β1 and ELF protein were detected by immunohistochemistry. The relationship between TGF-β1/ELF expression and patients' clinicopathologic factors was analyzed. The association between TGF-β1/ELF expression and disease-free survival and overall survival was analyzed by Kaplan-Meier curves, the log-rank test, and Multivariate Cox regression analyses. The expression of TGF-β1 in HCC tissues was significantly higher than that in normal liver tissues. Conversely, the expression of ELF in HCC tissues declined markedly. ELF protein was correlated with HBsAg, tumor size, tumor number, TNM and recurrence. Data also indicated a significant negative correlation between ELF and TGF-β1. Patients with high TGF-β1 expression or/and low ELF expression appeared to have a poor postoperative disease-free survival and overall survival compared with those with low TGF-β1 expression or/and high ELF expression. Furthermore, the predictive range of ELF combined with TGF-β1 was more sensitive than that of either one alone. TGF-β1 and ELF protein are potential and reliable biomarkers for predicting prognosis in HCC patients after hepatic resection. Our current study has demonstrated that the prognostic accuracy of testing can be enhanced by their combination.
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    ABSTRACT: Hepatocellular carcinoma (HCC) is a common complication in patients with chronic viral hepatitis and liver cirrhosis. Detection of HCC at an early stage is critical for a favorable clinical outcome. This is a case-control, hospital-based study, aimed to determine the usefulness of Lens Culinaris Agglutinin-Reactive Fraction of Alpha Fetoprotein (AFP-L3) as an early diagnostic marker for HCC in Sudanese Patients with chronic liver diseases. Blood samples were collected from 25 patients with HCC, 32 patients with chronic liver diseases (cirrhosis and chronic HBV/HCV), and 30 healthy individuals as control. AFP-L3 and Total Alpha Fetoprotein (T.AFP) were measured by immunometric assay. AFP-L3 and T.AFP were elevated in all patients (chronic liver disease and HCC patients). Both markers were found to be elevated with the increase of tumor size, and with presence of focal liver lesion (being elevating with the increase of number of lesions).Both markers showed to be elevated until a year after onset of the disease, then, decreased by time. AFP-L3 and T.AFP were positively correlated with the increase of patient's age, but no significant difference was found between males and females in all types of patients. AFP-L3 is more specific for HCC, this encourage us to use AFP-L3 as adjunct marker for HCC diagnosis.
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    ABSTRACT: Liver cancer is the fifth most common cancer, but the second leading cause of cancer death, in the world, with more than 700,000 fatalities annually. The major etiology of liver cancer is infection with an hepatotropic virus such as hepatitis B virus or hepatitis C virus infection. While chronic viral infection remains the main cause of liver disease and risk of hepatocellular carcinoma (HCC), rates of nonviral-associated HCC are occurring at an alarmingly increasing rate. Like many cancers, survival rates are closely associated with time of detection. If HCC is caught early, survival rates can be as high as 50%. Regrettably, most cases of HCC are caught late where survival rates can be as low as 2-7%. Thus, there has been great interest in discovering serum biomarkers that could be used to identify those with HCC. To this end, many groups have examined the N-linked glycans to identify changes that occur with HCC. As the liver secretes the vast majority of proteins into the serum, this has often been a starting point for study. In serum, alterations in core fucosylation, outer-arm fucosylation, increased sialylation, and glycan branching have been observed in patients with HCC. Similar findings have been found directly in HCC tissue suggesting that these glycan changes may play a role in tumor formation and development. © 2015 Elsevier Inc. All rights reserved.


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May 28, 2014