Des-γ-Carboxy Prothrombin and α-Fetoprotein as Biomarkers for the Early Detection of Hepatocellular Carcinoma

Lok, Anna S.; Sterling, Richard K.; Everhart, James E.; Wright, Elizabeth C.; Hoefs, John C.; Bisceglie, Adrian M. Di; Morgan, Timothy R.; Kim, Hae‐Young; Lee, William M.; Bonkovsky, Herbert L.; Dienstag, Jules L.

doi:10.1053/j.gastro.2009.10.031

Cited by 525 publications

(419 citation statements)

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“…Several other studies have shown DCP and AFP to be complementary, which is consistent with the production of DCP and AFP in HCC occurring through different pathways, possibly explaining why sex, race, underlying liver disease, and hepatic disease etiologies had opposite effects on these 2 markers [46][47][48].…”

Section: Discussionsupporting

confidence: 60%

758 Frequency of Elevated Biomarkers in Patients With Cryptogenic Hepatocellular Carcinoma

Taura¹,

Ichikawa²,

Miyaaki³

et al. 2012

Journal of Hepatology

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Background:The incidence of hepatocellular carcinoma (HCC) continues to increase in Japan, but the clinical characteristics of Japanese patients with HCC have not been well described. The aim of this study was to determine the frequencies and utilities of elevated a-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) levels as biomarkers in cryptogenic HCC. Material/Methods:A total of 2638 patients with HCC diagnosed between 1999 and 2010 in the Nagasaki Association Study of Liver (NASLD) were recruited for this study. The cause of HCC was categorized into 4 groups; HCC-B, HCC-C, HCC-BC, and HCC-nonBC. The significance of factors was examined for HCC-nonBC using logistic regression analysis in all patients. Results:Multivariate analysis identified age, sex, BMI, alcohol consumption, platelet count, AST, ALT, AFP, DCP, and TNM stage as independent and significant risk factors for HCC-nonBC. According to TNM stage, the median AFP levels in HCC-nonBC with TNM stages I, II, and III were significantly lower than in either HCC-B or HCC-C. In TNM stage IV, the median AFP level in HCC-nonBC was significantly lower than in either HCC-B or HCC-BC. The median DCP levels in HCC-nonBC with TNM stages I and II were significantly higher than those in either HCC-B or HCC-C. In TNM stage III, the median DCP level in HCC-nonBC was significantly higher than that in HCC-C. Conclusions:DCP was more sensitive than AFP for the diagnosis of early stage cryptogenic HCC. DCP should be used as the main serum test for cryptogenic HCC detection.

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Section: Discussionsupporting

confidence: 60%

758 Frequency of Elevated Biomarkers in Patients With Cryptogenic Hepatocellular Carcinoma

Taura¹,

Ichikawa²,

Miyaaki³

et al. 2012

Journal of Hepatology

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“…Various biomarkers, including α-fetoprotein (AFP) (13), des-γ-ca rboxy prothrombin (14) and α-l-fucosidase (15), have been identified over the past three decades. However, accurate indicators for the prognosis of HCC are limited.…”

Section: Introductionmentioning

confidence: 99%

High expression of ubiquitin-conjugating enzyme E2A predicts poor prognosis in hepatocellular carcinoma

Shen

et al. 2018

Oncol Lett

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Abstract. The present study aimed to illustrate the association of the expression of ubiquitin-conjugating enzyme E2A (UBE2A) with the clinicopathological parameters and prognosis in hepatocellular carcinoma (HCC). The expression levels of UBE2A mRNA and protein in a total of 276 HCC tissues and six liver cell lines was detected by fluorescent quantitative polymerase chain reaction, western blotting and immunohistochemistry. Statistical analysis was also performed to assess the association of the expression of UBE2A with the clinicopathological parameters and prognosis by the GraphPad Prism and SPSS version 21.0 software. UBE2A mRNA and protein were highly expressed in HCC tissues compared with those in the adjacent normal tissue. Immunohistochemical analysis revealed that UBE2A protein was more strongly stained in the 276 paraffin-embedded HCC tissues as compared with the 63 adjacent normal tissue. Statistical analysis also demonstrated that UBE2A expression was significantly associated with histological differentiation, TNM stage and vascular invasion of HCC (P<0.05). Notably, HCC patients with a high expression of UBE2A had a shorter survival time as compared with those with a low expression of UBE2A. There results suggested that UBE2A may be involved in the pathogenesis of HCC and may serve as an important prognostic marker.Further exploration of the involvement of UBE2A in HCC development may provide novel therapeutic targets. IntroductionHepatocellular carcinoma (HCC) is the third leading cause of cancer-associated mortality worldwide and the fifth most common cancer type (1). HCC is a global health burden and its prevalence varies worldwide (2). The incidence rate is reported to be higher in Asia (>20 cases/100,000 individuals) in comparison with that in North America and Europe (<5 cases/100,000 individuals) (3). The prognosis of HCC is poor, as evident by the fact that the number of annual mortality cases (~600,000) is almost equal to the number of new cases diagnosed annually (4). The median rate for 1-year survival is 80% (range, 63-97%), for 3-year survival is 70% (range, 34-78%) and for 5-year survival is 50% (range, 17-69%) (5). Surgery remains the most important treatment strategy for patients with HCC. The 5-year survival rate of patients with early HCC subsequent to resection treatment reaches 50%, although these patients exhibit a high recurrence rate (6,7). Despite advances in the diagnosis (8) and treatment (9) of HCC, the prognosis of this disease remains poor (10). Therefore, further clarification of the mechanisms underlying its development is important (11,12).At present, the prognosis of HCC is predicted based on imaging findings and biomarkers. Various biomarkers, including α-fetoprotein (AFP) (13), des-γ-ca rboxy prothrombin (14) and α-l-fucosidase (15), have been identified over the past three decades. However, accurate indicators for the prognosis of HCC are limited. Consequently, there is an urgency to develop a novel biomarker for the prognosis of HCC.The ubiquitin system serves a ...

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“…However, neither DCP nor AFP were proven to be optimal. 21 Problems associated with these surveillance programmes are various biases like lead-time bias (apparent improvement in survival), prognostic selection bias (identification of patients with slow progressive tumors who are more likely to live longer) and over diagnosis bias (false positives). However, there are studies which show a benefit despite statistically adjusting for lead time bias.…”

Section: Surveillancementioning

confidence: 99%

Role of Surveillance in Prevention of Hepatocellular Carcinoma

Panda

2014

Journal of Clinical and Experimental Hepatology

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Hepatocellular carcinoma is a common malignancy and one of the important public health problems in India. The surveillance of hepatocellular carcinoma (HCC) is an established approach to detect early cancers in patients with defined risks. However, there are still controversies and issues to be addressed regarding the optimal surveillance methods and interval. The current level of awareness among physicians in India about surveillance is low and the need and most cost effective surveillance strategy in developing country like ours is unclear. This article has tried to discuss these issues in their appropriate perspective. To address this complicated issue, a multicenter randomized prospective study however may be required. ( J CLIN EXP HEPATOL 2014;4:S43-S49) H epatocellular carcinoma (HCC) is the fifth commonest cancer worldwide and third commonest cause of cancer related mortality. 1 In India, the mean incidence of HCC as per four population-based registries was 2.77% for males and 1.38% for females. The prevalence of HCC in India varies from 0.2% to 1.6%. 2,3 It is interesting to note that the consolidated data from cancer registries of India do not reflect HCC as an important malignancy. 4 Risk of HCC development is high in patients with liver cirrhosis of any etiology, particularly with chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. 5 Since India has a high prevalence of HBV infection (4% of population, i.e about 40 million Indians) 6 as well as HCV infection (0.3-1.5%) it could contribute to the high incidence of HCC. 7 Other risk factors for HCC like high prevalence of Nonalcoholic Fatty Liver Disease (NAFLD) obesity, diabetes, alcohol consumption among males are also present in India.Nonalcoholic Fatty Liver Disease (NAFLD) particularly its more aggressive form, nonalcoholic steatohepatitis (NASH) is an important factor which can lead to cirrhosis and HCC. It is estimated that nearly two-thirds of obese people have some form of fatty liver, ranging from steatosis to NASH. NASH can progress to liver cirrhosis in 3%-15% and subsequently to liver cancer. 8 A study by Prasad et al showed that age-standardized prevalence rates of metabolic syndrome were 33.5% overall, 24.9% in males and 42.3% in females in India. Authors concluded that metabolic syndrome is a significant public health problem even in one of the poorest states of India. 9 Hence NASH is particularly important in countries like India where metabolic syndrome is on the rise.It is important to note that in the absence of an effective screening program and only 7% of population being covered by cancer registries, under reporting cannot be ruled out. 10 A recent study in which 130 trained physicians independently assigned causes to 122429 deaths, which occurred in 1$1 million homes in 6671 small areas that were randomly selected to be representative of all of India, based on a structured nonmedical surveyor's field report has put the liver cancer as the 4th commonest cause of death in male and 8th commonest cause of death i...

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Des-γ-Carboxy Prothrombin and α-Fetoprotein as Biomarkers for the Early Detection of Hepatocellular Carcinoma

Cited by 525 publications

References 36 publications

758 Frequency of Elevated Biomarkers in Patients With Cryptogenic Hepatocellular Carcinoma

758 Frequency of Elevated Biomarkers in Patients With Cryptogenic Hepatocellular Carcinoma

High expression of ubiquitin-conjugating enzyme E2A predicts poor prognosis in hepatocellular carcinoma

Role of Surveillance in Prevention of Hepatocellular Carcinoma

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