Serum Markers of Hepatocellular Carcinoma

Department of Biomedical Science, University of Catania, Via Androne 83, 95124, Catania, Italy.
Digestive Diseases and Sciences (Impact Factor: 2.61). 03/2010; 55(10):2744-55. DOI: 10.1007/s10620-010-1184-7
Source: PubMed


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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    • "However, its sensitivity for detecting HCC ranges between 25%-60%, and its specificity is also low because it can also be detected in patients with cirrhosis (11%-47%) and chronic hepatitis (15%-58%) (El-Serag et al., 2008; El-Attar et al., 2010; Xu et al., 2012). Increasing cut-off values can improve its specificity up to 76%, but on the other hand a corresponding decrease in sensitivity (maximum 60%) is observed (Lok et al., 2010; Bertino et al., 2012). Serum concentration of 20 ng/mL is the most commonly used cutoff value to distinguish HCC patients from healthy adults in clinical researches. "
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    ABSTRACT: Abstract PURPOSE: To find parameters that can increase alpha-fetoprotein (AFP) sensitivity and so help in accurate diagnosis and rapid management of hepatocullular carcinoma (HCC), as AFP has limited utility of distinguishing HCC from benign hepatic disorders for its high false-positive and false negative rates. MATERIALS AND METHODS: Serum levels of AFP, 5'-nucleotidase enzyme activity (5-NU) and leucine aminopeptidase enzyme (LAP) activity were measured in 40 individuals. RESULTS: LAP and 5'NU were elevated in HCC at p<0.001. Pearson correlation coefficients showed that changes in AFP exhibited positive correlation with both 5'-NU and LAP at (p<0.001). The complementary use of LAP only with AFP resulted in an increase in sensitivity of AFP from 75% to 90% in detecting HCC. The complementary use of both LAP and 5-NU with AFP resulted in an increased sensitivity of AFP in detecting HCC from 75% to 95%. CONCLUSIONS: LAP and 5-FU can be determined in HCC patients in combination with AFP to improve its sensitivity and decrease false negative results.
    Full-text · Article · Mar 2015 · Asian Pacific journal of cancer prevention: APJCP
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    • "Because elevation of serum AFP, a common marker for hepatocellular carcinoma (HCC), also occurs in non-HCC conditions such as pregnancy, AFP-L3, consisting of core-fucosylated glycoforms of AFP, provides better specificity for HCC. AFP-L3 levels have been found to be related to progression from moderately differentiated to poorly differentiated tumors, therefore, it may be used as an early diagnosis of HCC when the tumor diameter is <2 cm [80]. Similarly, in order to discover potential glycosylated-proteins biomarkers in ovarian cancer, Wu et al. applied a lectin array and Exactag labeling based quantitative glycoproteomics approach. "
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    ABSTRACT: Glycosylation is estimated to be found in over 50% of human proteins. Aberrant protein glycosylation and alteration of glycans are closely related to many diseases. More than half of the cancer biomarkers are glycosylated-proteins, and specific glycoforms of glycosylated-proteins may serve as biomarkers for either the early detection of disease or the evaluation of therapeutic efficacy for treatment of diseases. Glycoproteomics, therefore, becomes an emerging field that can make unique contributions to the discovery of biomarkers of cancers. The recent advances in mass spectrometry (MS)-based glycoproteomics, which can analyze thousands of glycosylated-proteins in a single experiment, have shown great promise for this purpose. Herein, we described the MS-based strategies that are available for glycoproteomics, and discussed the sensitivity and high throughput in both qualitative and quantitative manners. The discovery of glycosylated-proteins as biomarkers in some representative diseases by employing glycoproteomics was also summarized.
    Full-text · Article · May 2014 · Clinical Proteomics
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    • "Several reports have described an association of VKDPs with different types of cancer, namely, matrix Gla protein (MGP) and uncarboxylated prothrombin (des-γ-carboxy prothrombin, DCP) [22–28]. Although a relation between MGP γ-carboxylation status and neoplasias is still unknown, for prothrombin it was shown that increased circulating DCP can be used as a diagnostic and prognostic marker for hepatocellular carcinoma [22, 28, 29]. It is remarkable that, despite the widely reported vitamin K anticancer potential [[10, 30], and references therein], its mechanism of action in cancerous processes remains elusive. "
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    ABSTRACT: Gla-rich protein (GRP) was described in sturgeon as a new vitamin-K-dependent protein (VKDP) with a high density of Gla residues and associated with ectopic calcifications in humans. Although VKDPs function has been related with γ-carboxylation, the Gla status of GRP in humans is still unknown. Here, we investigated the expression of recently identified GRP spliced transcripts, the γ-carboxylation status, and its association with ectopic calcifications, in skin basal cell and breast carcinomas. GRP-F1 was identified as the predominant splice variant expressed in healthy and cancer tissues. Patterns of γ-carboxylated GRP (cGRP)/undercarboxylated GRP (ucGRP) accumulation in healthy and cancer tissues were determined by immunohistochemistry, using newly developed conformation-specific antibodies. Both GRP protein forms were found colocalized in healthy tissues, while ucGRP was the predominant form associated with tumor cells. Both cGRP and ucGRP found at sites of microcalcifications were shown to have in vitro calcium mineral-binding capacity. The decreased levels of cGRP and predominance of ucGRP in tumor cells suggest that GRP may represent a new target for the anticancer potential of vitamin K. Also, the direct interaction of cGRP and ucGRP with BCP crystals provides a possible mechanism explaining GRP association with pathological mineralization.
    Full-text · Article · Apr 2014 · BioMed Research International
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