ABSTRACT
ABSTRACT: Alpha fetoprotein (AFP) level is the gold standard diagnostic tool for detection and monitoring hepatocellular carcinoma (HCC) but with low sensitivity. Thus, the identification of alternative or combined serum markers of HCC is highly needed. Therefore, the aim of this work was to verify the value of serum midkine (MDK), Dickkopf-related protein 1 (DKK1), and alpha-L-fucosidase (AFU) in detection of HCC.We recruited 244 subjects to the present study; 89 with liver cirrhosis, 86 cirrhotic hepatitis C virus (HCV) induced HCC, and 69 apparently healthy volunteers as controls. Serum AFP, MDK, DKK1, and AFU were measured by ELISA.Patients with HCC showed significantly higher serum MDK, DKK1, and AFU levels compared with those patients with liver cirrhosis and healthy controls (X2â=â179.56, 153.94, and 90.07 respectively) (Pâ<â.001 in all). In HCC cases, neither of MDK, DKK1, or AFU was correlated with tumor number. On the other hand, only serum DKK1 was significantly higher in lesions >5âcm, those with portal vein thrombosis and advanced HCC stage. Receiver operator characteristic (ROC) curve analysis showed that serum MDK levels discriminated between cirrhosis and HCC at a sensitivity of 100%, a specificity of 90% at cut-off value of >5.1âng/mL.Although our results showed that serum MDK, DKK-1, and AFU are increased in HCC cases only MDK may be considered as the most promising serological marker for the prediction of the development of HCC in cirrhotic HCV patients.
Subject(s)
Carcinoma, Hepatocellular/diagnosis , Hepatitis C/blood , Liver Cirrhosis/blood , Liver Neoplasms/diagnosis , Midkine/blood , Biomarkers, Tumor/blood , Carcinoma, Hepatocellular/virology , Case-Control Studies , Cross-Sectional Studies , Female , Hepacivirus , Hepatitis C/complications , Hepatitis C/virology , Humans , Intercellular Signaling Peptides and Proteins/blood , Liver Cirrhosis/complications , Liver Cirrhosis/virology , Liver Neoplasms/virology , Male , Middle Aged , Predictive Value of Tests , ROC Curve , Sensitivity and Specificity , alpha-L-Fucosidase/bloodABSTRACT
Objective: Hepatocellular carcinoma (HCC) is a lethal global disease that requires an accurate diagnosis. We assessed the potential of 5 serum biomarkers (AFP, AFU, GGT-II, GPC3, and HGF) in the diagnosis of HCC. Methods: In this retrospective study, we measured the serum levels of each biomarker using ELISAs in 921 participants, including 298 patients with HCC, 154 patients with chronic hepatitis (CH), 122 patients with liver cirrhosis (LC), and 347 healthy controls from 3 hospitals. Patients negative for hepatitis B surface antigen and hepatitis C antibody (called "NBNC-HCC") and patients positive for the above indices (called "HBV-HCC and HCV-HCC") were enrolled. The selected diagnostic model was constructed using a training cohort (n = 468), and a validation cohort (n = 453) was used to validate our results. Receiver operating characteristic analysis was used to evaluate the diagnostic accuracy. Results: The α-L-fucosidase (AFU)/α-fetoprotein (AFP) combination was best able to distinguish NBNC-HCC [area under the curve: 0.986 (95% confidence interval: 0.958-0.997), sensitivity: 92.6%, specificity: 98.9%] from healthy controls in the test cohort. For screening populations at risk of developing HCC (CH and LC), the AFP/AFU combination improved the diagnostic specificity for early-stage HCC [area under the curve: 0.776 (0.712-0.831), sensitivity: 52.5%, specificity: 91.6% in the test group]. In all-stage HBV-HCC and HCV-HCC, AFU was also the best candidate biomarker combined with AFP [area under the curve: 0.835 (0.784-0.877), sensitivity 69.1%, specificity: 87.4% in the test group]. All results were verified in the validation group. Conclusions: The AFP/AFU combination could be used to identify NBNC-HCC from healthy controls and hepatitis-related HCC from at-risk patients.
Subject(s)
Biomarkers, Tumor/blood , Carcinoma, Hepatocellular/diagnosis , Liver Neoplasms/diagnosis , Adult , Aged , Aged, 80 and over , Carcinoma, Hepatocellular/blood , Case-Control Studies , Female , Hepatitis B Surface Antigens/blood , Humans , Liver Cirrhosis/blood , Liver Cirrhosis/diagnosis , Liver Neoplasms/blood , Male , Middle Aged , ROC Curve , Retrospective Studies , Sensitivity and Specificity , Young Adult , alpha-Fetoproteins/analysis , alpha-L-Fucosidase/bloodABSTRACT
BACKGROUND: Early detection of hepatocellular carcinoma (HCC) among hepatitis B virus (HBV)-infected patients remains a challenge, especially in China. We sought to create an online calculator of serum biomarkers to detect HCC among patients with chronic hepatitis B (CHB). METHODS: Participants with HBV-HCC, CHB, HBV-related liver cirrhosis (HBV-LC), benign hepatic tumors, and healthy controls (HCs) were recruited at 11 Chinese hospitals. Potential serum HCC biomarkers, protein induced by vitamin K absence or antagonist-II (PIVKA-II), α-fetoprotein (AFP), lens culinaris agglutinin A-reactive fraction of AFP (AFP-L3) and α-l-fucosidase (AFU) were evaluated in the pilot cohort. The calculator was built in the training cohort via logistic regression model and validated in the validation cohort. RESULTS: In the pilot study, PIVKA-II and AFP showed better diagnostic sensitivity and specificity compared with AFP-L3 and AFU and were chosen for further study. A combination of PIVKA-II and AFP demonstrated better diagnostic accuracy in differentiating patients with HBV-HCC from patients with CHB or HBV-LC than AFP or PIVKA-II alone [area under the curve (AUC), 0.922 (95% CI, 0.908-0.935), sensitivity 88.3% and specificity 85.1% for the training cohort; 0.902 (95% CI, 0.875-0.929), 87.8%, and 81.0%, respectively, for the validation cohort]. The nomogram including AFP, PIVKA-II, age, and sex performed well in predicting HBV-HCC with good calibration and discrimination [AUC, 0.941 (95% CI, 0.929-0.952)] and was validated in the validation cohort [AUC, 0.931 (95% CI, 0.909-0.953)]. CONCLUSIONS: Our results demonstrated that a web-based calculator including age, sex, AFP, and PIVKA-II accurately predicted the presence of HCC in patients with CHB. CLINICALTRIALSGOV IDENTIFIER: NCT03047603.
Subject(s)
Biomarkers, Tumor/blood , Carcinoma, Hepatocellular/diagnosis , Hepatitis B/complications , Adult , Aged , Algorithms , Area Under Curve , Asian People , Biomarkers/analysis , Biomarkers/blood , Carcinoma, Hepatocellular/blood , China , Female , Hepatitis B/blood , Hepatitis B virus , Humans , Liver Cirrhosis/blood , Liver Cirrhosis/diagnosis , Liver Neoplasms/blood , Liver Neoplasms/diagnosis , Male , Middle Aged , Pilot Projects , Protein Precursors/analysis , Protein Precursors/blood , Prothrombin/analysis , ROC Curve , Sensitivity and Specificity , alpha-Fetoproteins/analysis , alpha-L-Fucosidase/analysis , alpha-L-Fucosidase/bloodABSTRACT
BACKGROUND: Human α-fucosidase (EC 3.2.1.51) is a hydrolase the importance of which has been increasing in the latest years. However, data about its plasma level in children with autoimmune disorders, particularly Sjögren's syndrome (SS), are lacking. In this study, the plasma activity of L-α-fucosidase-1 (α-L-FUCA-1) was assayed in hospitalized children and adults and its association with SS and other rheumatic disorders further evaluated. METHODS: In total 73 Hungarian hospitalized patients, 32 children (2.5-10 years) and 41 adults (32-68 years), were enrolled in the study and underwent plasma assay of α-L-FUCA1 activity. Linear regression, Durbin-Watson (DW), and Pearson tests were evaluated to investigate the relationship between α-L-FUCA-1 plasma levels and autoimmune manifestations. RESULTS: α-L-FUCA-1 correlated with SS both in children (2-sided t test, P = 0.0023) and in adults (2-sided t test, P = 0.00035). Linear regressions showed that in other rheumatic disorders, α-L-FUCA1 did not show any differential distribution related to the particular pathology (r = 0.2042, P = 0.1531, DW test = 2.2139 positive), while this trend was radically opposite for patients with SS (r = 0.1462, P = 0.0032, DW test = 1.3664, negative). CONCLUSIONS: Alterations in plasma level of α-L-FUCA-1 were significantly associated with SS. This preliminary result should encourage further research on α-L-FUCA-1 as a possible differential serological marker of SS.
Subject(s)
Sjogren's Syndrome/blood , alpha-L-Fucosidase/blood , Adult , Biomarkers/blood , Child , Child, Preschool , Female , Humans , Hungary , Male , Middle Aged , Predictive Value of Tests , Prognosis , Sjogren's Syndrome/diagnosis , Sjogren's Syndrome/enzymologyABSTRACT
Aim: To evaluate the diagnostic performance of serum AFU for early stage hepatocellular carcinoma (HCC). Methods: Concentration of AFU and AFP were measured in 512 patients. The performance was compared for AFU and AFP alone or in combination. Results: The area under the curve (AUC) for AFU was 0.68, with a sensitivity of 56.1% and specificity of 69.2% at the cut-off value of 24 U/l; whereas the AUC for AFP was 0.83, with a sensitivity of 58.2% and specificity of 85.2% at cut-off value of 20 ng/ml. The AUC of AFU alone or the combination with AFP were lower than that of AFP alone. Conclusion: AFU is a suboptimal biomarker for early detection of HCC.
Subject(s)
Carcinoma, Hepatocellular/diagnosis , Carcinoma, Hepatocellular/enzymology , Early Detection of Cancer , Liver Neoplasms/diagnosis , Liver Neoplasms/enzymology , alpha-L-Fucosidase/blood , Adolescent , Adult , Aged , Aged, 80 and over , Carcinoma, Hepatocellular/blood , Carcinoma, Hepatocellular/pathology , Female , Humans , Liver Neoplasms/blood , Liver Neoplasms/pathology , Male , Middle Aged , Neoplasm Staging , Tumor Burden , Young Adult , alpha-Fetoproteins/metabolismABSTRACT
Fucosylated glycans are essential molecules that facilitate signal transductions in several signal pathways and play important roles in development, inflammation, infection, and tumor metastasis. The fucosylated glycans are difficult to be developed into clinical biomarkers due to their complicated structures, but the decreased or increased activities of serum α-l-fucosidase, the lysosomal enzyme required for fucosylated glycan degradation, are diagnostic biomarker for patients with fucosidosis and hepatocellular carcinoma, respectively. However, the relationship between serum α-l-fucosidase activities and other human diseases is largely unknown. By taking advantage of the serum α-l-fucosidase activity data collected in the clinical laboratory of our hospital during the past 5 years, the serum α-l-fucosidase activities from 188,077 patients with 64 clinically defined diseases were compared to that of healthy controls (9519) with at least 30 data sets for each type of disease. Based on the mean, median, and -Log10p values, we found that patients with preeclampsia, liver cancer, hepatitis, psoriasis, and multiple myeloma had serum α-l-fucosidase activities higher, while patients with Wilms' tumor, breast cancer, hepatic encephalopathy, or postbreast surgery had comparable activities to that of healthy controls. Unexpectedly, patients with the rest of 36 diseases had the statistically lower levels of serum α-l-fucosidase activities compared to that of healthy controls. Moreover, patients with uremia, azotemia, myeloproliferative disorder, and Alzheimer's disease had lowest median levels of serum α-l-fucosidase activities among the 64 diseases studied. Taken together, our data showed that serum α-l-fucosidase activities are not only useful for liver cancer diagnosis but also valuable indicators for different types of human diseases.
Subject(s)
Pre-Eclampsia/blood , Pre-Eclampsia/enzymology , alpha-L-Fucosidase/blood , Case-Control Studies , Female , Humans , Pregnancy , Publications , RNA, Messenger/genetics , RNA, Messenger/metabolism , alpha-L-Fucosidase/geneticsABSTRACT
Hepatocellular carcinoma (HCC) is among the leading causes of mortality in the world. The detection of HCC in its early stage is the key for early treatment and thus the improvement of the chances of survival. Among the various methods of HCC screening, assays based on the detection of biomarker that is specific to HCC such as alpha-l-fucosidase (AFU) have been regarded as the most prominent methods. In this regards, a new assay for the detection of AFU to screen HCC was developed. This assay was based on the energy transfer between carbon dots (C-dots) and gold nanoparticles (AuNPs), the concentration of AFU could be monitored by the degree of C-dots fluorescence quenching due to the energy transfer. With this assay, a limit of detection of 3.4â¯nM (well below the diagnostic cutoff point of 80â¯nM), and a broad linear range of detection from 11.3 to 200â¯nM were achieved. We also demonstrate the determination of the concentration of AFU in human blood serum.
Subject(s)
Carbon/chemistry , Gold/chemistry , Immunoassay , Metal Nanoparticles/chemistry , alpha-L-Fucosidase/blood , Antibodies, Immobilized/chemistry , Antibodies, Immobilized/immunology , Biomarkers, Tumor/blood , Carcinoma, Hepatocellular/diagnosis , Citric Acid/chemistry , Fluorescein-5-isothiocyanate/chemistry , Humans , Limit of Detection , Liver Neoplasms/diagnosis , alpha-L-Fucosidase/immunologyABSTRACT
Cancers and many other diseases, such as hepatocellular carcinoma (HCC) and cardiovascular diseases (CVD), have threatened human lives for centuries. Therefore, a novel technique for such disease prediction is in an urgent demand for timely treatment. Biomarkers, alpha-L-fucosidase (AFU) for HCC and cardiac troponin I (cTnI) for CVD, have proven to be essential in the role of disease detection. Herein, we report on an ultrasensitive plasmonic biosensor that converts plasmonic absorption to electrical current in order to detect AFU and cTnI using whole human blood in a real-time and parallel fashion. The detection limit was calculated to be 0.016 U/L for AFU and 0.015 ng/mL for cTnI, respectively. Combined with the versatility of the strategies for different biomarkers, these results demonstrate that the developed biosensor exhibits a promising application for the prediction of cancers and many other diseases.
Subject(s)
Biosensing Techniques/methods , Blood Chemical Analysis/methods , Limit of Detection , Troponin I/blood , alpha-L-Fucosidase/blood , Humans , Time FactorsABSTRACT
PURPOSE: Adaptation of the colorimetric method for the determination of ß-d-galactosidase, ß-d-glucuronidase and α-l-fucosidase activities in serums from hemolyzed blood, the material currently being discarded. MATERIALS AND METHODS: The materials included serums from hemolyzed and non-hemolyzed blood, obtained from 26 healthy volunteers. The adaptation of the method involved precipitation of the proteins with trichloroacetic acid after incubating serums with substrates, but before determining the products of enzymatic reactions. RESULTS: In serums from hemolyzed and non-hemolyzed blood of the same persons, we found high correlations among the results obtained using hemolyzed blood (with adapted) and non-hemolyzed blood (with non-adapted) methods. CONCLUSION: We are able to determine the ß-d-galactosidase, ß-d-glucuronidase and α-l-fucosidase activities in serums from hemolyzed blood (with adapted) and non-hemolyzed blood (with non-adapted) methods, with the same accuracy and precision.
Subject(s)
Glucuronidase/blood , Hemolysis , alpha-L-Fucosidase/blood , beta-Galactosidase/blood , Adult , Female , Hemoglobins/metabolism , Humans , Hydrogen-Ion Concentration , Kinetics , Male , Middle Aged , Nitrophenols/metabolism , Young AdultABSTRACT
Alpha-L-fucosidase (AFU) has been reported to be a predictor of survival in patients with several cancers, but it is unclear whether AFU is associated with prognosis in patients with intrahepatic cholangiocarcinoma (iCCA). In this study, we used receiver operating characteristic (ROC) analysis to generate the cutoff point of AFU for overall survival (OS). The prognostic influence of the AFU level in serum on OS was studied using Kaplan-Meier curves. Moreover, invasion assays and Western blotting were performed to explore the effects of AFU on iCCA invasion in vitro. We found that higher AFU levels (≥20.85 U/L) were significantly associated with favorable median OS (44.3 months versus 20.1 months; P = 0.022) in iCCA patients. Cox regression models' analyses showed that the AFU level was an independent predictor for OS (P = 0.006). Moreover, our results revealed that the AFU could impair the invasion capability of the iCCA cells, HuH28, and also downregulated the expression of matrix metalloproteinase 2 and matrix metalloproteinase 9. In conclusion, our results indicate that AFU is a significantly favorable prognostic factor in iCCA patients.
Subject(s)
Bile Duct Neoplasms/blood , Bile Duct Neoplasms/pathology , Cholangiocarcinoma/blood , Cholangiocarcinoma/pathology , Neoplasm Invasiveness/pathology , alpha-L-Fucosidase/blood , Bile Duct Neoplasms/metabolism , Bile Ducts, Intrahepatic/pathology , Biomarkers, Tumor/blood , Cell Line, Tumor , Cholangiocarcinoma/metabolism , Down-Regulation/physiology , Female , Humans , Male , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 9/metabolism , Middle Aged , Prognosis , ROC Curve , Retrospective StudiesABSTRACT
The protective effect of zinc selenium tea against metabolic syndrome (MetS) was tested by using a high-sucrose-high-fat diet (HSHFD)-induced MetS model. Fifty Sprague-Dawley rats were randomly divided into five groups: normal diet (C-group), HSHFD (CH-group), HSHFD + green tea (0.24 g/kg/day) (TH-group), HSHFD + low-dose zinc selenium organic tea (0.24 g/kg/day) (ZTHL-group), and HSHFD + high-dose zinc selenium organic tea (1.20 g/kg/day) (ZTHH-group). After 8 weeks, compared to both the C-group and CH-group, the hepatosomatic index (HI) was significantly reduced in the ZTHL-group (p < 0.05). Fasting blood glucose (FBG) levels were highest in the TH-group, followed by the CH-group, then the ZTHL-group, then the ZTHH-group, and finally the C-group. Compared with the CH-group, the serum total cholesterol (TC) and low density lipid-cholesterol (LDL-C) concentrations were significantly lower in the ZTHH-group (p < 0.05). Significant decreases in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bile acids (TBA), alkaline phosphatase (ALP), and direct bilirubin (DBIL) levels were observed in ZTHL-group versus the CH-group (p < 0.05). Serum alpha-L-fucosidase (AFU) levels in the ZTHH-group were lower than in the CH-group (P < 0.01). Histopathological examination of the liver and fat biopsies illustrates that the liver cells showed a decrease in the extent of necrosis and dropsy in the ZTHL-group and ZTHH-group versus the CH-group. Zinc selenium tea showed a protection effect against hepatic damage.
Subject(s)
Antioxidants/pharmacology , Hypoglycemic Agents/pharmacology , Metabolic Syndrome/drug therapy , Obesity/drug therapy , Selenium Compounds/pharmacology , Tea/chemistry , Zinc Compounds/pharmacology , Adipose Tissue/drug effects , Adipose Tissue/metabolism , Adipose Tissue/pathology , Alanine Transaminase/blood , Alkaline Phosphatase/blood , Animals , Aspartate Aminotransferases/blood , Bilirubin/blood , Blood Glucose/metabolism , Cholesterol, LDL/antagonists & inhibitors , Cholesterol, LDL/blood , Diet, High-Fat/adverse effects , Dose-Response Relationship, Drug , Fasting , Female , Liver/drug effects , Liver/metabolism , Liver/pathology , Liver Function Tests , Male , Metabolic Syndrome/blood , Metabolic Syndrome/etiology , Metabolic Syndrome/pathology , Obesity/blood , Obesity/etiology , Obesity/pathology , Rats , Rats, Sprague-Dawley , Sucrose/administration & dosage , alpha-L-Fucosidase/bloodABSTRACT
Human α-fucosidase (EC 3.2.1.51) is an enzyme (hydrolase) of particular biological and medical interest, as the inherited deficiency in its activity leads to fucosidosis, a pathology belonging to severe glycoprotein lysosomal storage disorders. Although its importance has increased in latest years, data about its plasma level in children with inflammatory disorders are still lacking. In the present study, plasma activity of α-L-fucosidase-1 (FUCA-1) and its potential association with chronic inflammatory pathologies was evaluated in hospitalized individuals, both pediatric and adult ones. A number of 201 Hungarian hospitalized patients, 144 children (1-13 years) and 57 adults (31-88 years), were enrolled in the study and underwent plasma assay of FUCA-1 activity, following the normal routine analytical run in the hospital service. Regression and Pearson tests were evaluated to investigate the relationship between FUCA-1 plasma levels and inflammatory disorders diagnosed with subjects recruited in the study. No correlation of FUCA-1 activity was observed in the pediatric patients with immune (p = 0.9677) or metabolic (p = 0.6974) disorders, but a correlation was reported when comparing clusters of chronic inflammatory and autoimmune disease vs. controls (p < 0.05). Furthermore, a relationship was found between FUCA-1 activity in plasma and inflammatory disorders and autoimmunity both in adults and in the pediatric cohort of patients (Pearson test, p = 0.000148). Alterations in plasma levels of FUCA-1 were significantly associated with chronic inflammatory and autoimmune disorders, both in children and adults. The result of the present study should encourage further research on FUCA-1 as a marker of chronic inflammation and autoimmunity.
Subject(s)
Autoimmune Diseases/metabolism , Inflammation/metabolism , alpha-L-Fucosidase/blood , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Cohort Studies , Female , Fucosidosis/genetics , Hospitalization , Humans , Hungary , Infant , Male , Middle Aged , alpha-L-Fucosidase/geneticsABSTRACT
Detection of alpha-l-fucosidase has been shown to have relevance in diagnosing hepatocellular carcinoma. Few assays have been developed to measure this enzyme, with most relying on colorimetric techniques involving the enzyme's kinetics. While these assays are facile and quick, the sensitivity is not always sufficient for early tumor detection. To improve upon previous assays for alpha-l-fucosidase, a fluorescence based immunoassay was produced implementing an alpha-l-fucosidase specific antibody (FUCA2). The immobilization of the alpha-l-fucosidase-specific antibody onto a quartz slide was investigated with several bioconjugation approaches and an immunoassay for detection of alpha-l-fucosidase was produced. The immunoassay was utilized to produce calibration curves for quantifying alpha-l-fucosidase concentrations in both PBS and human blood serum. A detection limit of 10 nM was found using human blood serum, which is well below the diagnostic cutoff point of 80 nM.
Subject(s)
Carcinoma, Hepatocellular/blood , Carcinoma, Hepatocellular/diagnosis , Immunoassay/methods , Liver Neoplasms/blood , Liver Neoplasms/diagnosis , alpha-L-Fucosidase/blood , Biomarkers, Tumor/blood , Early Diagnosis , Humans , Limit of DetectionABSTRACT
AIM: To explore the association between serum α-L-fucosidase (AFU) and non-alcoholic fatty liver disease (NAFLD). METHODS: A total of 16473 individuals (9456 men and 7017 women) were included in the current study, who presented for a health examination at the First Affiliated Hospital of Zhejiang University School of Medicine in 2014. The baseline characteristics of the cohort were compared by NAFLD status. Linear regression analysis and stepwise multiple regression analysis were applied to assess the risk factors for NAFLD. Receiver operating characteristic curve was used to determine the sensitivity and specificity of AFU in the diagnosis of NAFLD. RESULTS: The prevalence rates of NAFLD and metabolic syndrome (MetS) were 38.0% and 25.4%, respectively. The NAFLD group had significantly higher AFU levels than the non-NAFLD group (28.7 ± 7.9 U/L vs 26.0 ± 7.3 U/L, P < 0.001) and the prevalence rate of NAFLD increased with progressively higher serum AFU levels. AFU was positively correlated with MetS and its five components: central obesity, hypertriglyceridemia, low high-density lipoprotein cholesterol, and elevated blood pressure and fasting glucose. Stepwise multiple logistic regression analysis showed that AFU was associated with an increased risk of NAFLD (OR = 1.009, 95%CI: 1.003-1.014, P < 0.001). The best cut-off value of AFU for the diagnosis of NAFLD was 27.5 U/L. The area under the curve (diagnostic efficacy index) was 0.606. The sensitivity and specificity were 54.6% and 61.8%, respectively. CONCLUSION: AFU level is significantly associated with NAFLD, and elevated AFU level is an independent risk factor for NAFLD.
Subject(s)
Metabolic Syndrome/blood , Non-alcoholic Fatty Liver Disease/blood , alpha-L-Fucosidase/blood , Adult , Area Under Curve , Biomarkers/blood , Chi-Square Distribution , China/epidemiology , Cross-Sectional Studies , Female , Humans , Linear Models , Logistic Models , Male , Metabolic Syndrome/diagnosis , Metabolic Syndrome/enzymology , Metabolic Syndrome/epidemiology , Middle Aged , Multivariate Analysis , Non-alcoholic Fatty Liver Disease/diagnosis , Non-alcoholic Fatty Liver Disease/enzymology , Non-alcoholic Fatty Liver Disease/epidemiology , Odds Ratio , Predictive Value of Tests , Prevalence , ROC Curve , Reproducibility of Results , Risk Factors , Up-RegulationABSTRACT
Rumex vesicarius is an edible herb distributed in Egypt and Saudi Arabia. The whole plant has significant value in folk medicine and it has been used to alleviate several diseases. Hepatocellular carcinoma (HCC), the major primary malignant tumor of the liver, is one of the most life-threatening human cancers. The goal of the current study was to explore the potent role of Rumex vesicarius extract against HCC induced in rats. Thirty adult male albino rats were divided into 3 groups: (I): Healthy animals received orally 0.9% normal saline and served as negative control group, (II): HCC group in which rats were orally administered N-nitrosodiethylamine NDEA, (III): HCC group treated orally with R. vesicarius extract in a dose of 400 mg/kg b.wt daily for two months. ALT and AST, ALP and γ-GT activities were estimated. CEA, AFP, AFU, GPC-3, Gp-73 and VEGF levels were quantified. Histopathological examination of liver tissue sections was also carried out. The results of the current study showed that the treatment of the HCC group with R. vesicarius extract reversed the significant increase in liver enzymes activity, CEA, AFP, AFU, glypican 3, golgi 73 and VEGF levels in serum as compared to HCC-untreated counterparts. In addition, the favorable impact of R. vesicarius treatment was evidenced by the marked improvement in the histopathological features of the liver of the treated group. In conclusion, the present experimental setting provided evidence for the significance of R. vesicarius as anticancer candidate with a promising anticancer potential against HCC. The powerful hepatoprotective properties, the potent antiangiogenic activity and the effective antiproliferative capacity are responsible for the anticancer effect of this plant.
Subject(s)
Antineoplastic Agents, Phytogenic/therapeutic use , Carcinoma, Hepatocellular/drug therapy , Liver Neoplasms, Experimental/drug therapy , Phytotherapy , Plant Extracts/therapeutic use , Rumex , Alanine Transaminase/blood , Alkaline Phosphatase/blood , Animals , Aspartate Aminotransferases/blood , Carcinoembryonic Antigen/blood , Carcinoma, Hepatocellular/blood , Carcinoma, Hepatocellular/chemically induced , Carcinoma, Hepatocellular/pathology , Diethylnitrosamine , Glycoproteins/blood , Glypicans/blood , Liver Neoplasms, Experimental/blood , Liver Neoplasms, Experimental/chemically induced , Liver Neoplasms, Experimental/pathology , Male , Rats , Rats, Wistar , Vascular Endothelial Growth Factor A/blood , alpha-Fetoproteins/metabolism , alpha-L-Fucosidase/blood , gamma-Glutamyltransferase/bloodABSTRACT
Hepatocellular carcinoma (HCC) surveillance lacks a reliable biomarker. Alpha-fetoprotein (AFP) is the most widely used. However, not all HCCs secrete AFP. AFP may be elevated with cirrhosis in the absence of HCC. Serum alpha-L-fucosidase (AFU) and squamous cell carcinoma antigen-immunoglobulin M complex (SCCA-IgM) were found to be useful markers in diagnosing HCC. SCCA-IgM and AFU were assessed by ELISA technique; AFP was measured by enzyme chemiluminescence in serum of 40 patients with HCC, 30 patients with liver cirrhosis, and 20 healthy control participants to compare their accuracy in early diagnosis of HCC. Serum SCCA-IgM and AFU levels were significantly elevated in HCC group compared to cirrhotic group (P value<0.001 and <0.001, respectively). Receiver operating characteristic curve showed the optimal cutoff value for SCCA-IgM was 233 AU/ml with sensitivity 87.5% and specificity 66% and for AFU was 25 U/L with sensitivity 87.5% and specificity 98%. AFP cutoff value was 48 ng/mL with sensitivity of 70% and specificity of 53.3%. The simultaneous determination of AFP and SCCA-IgM activity increased the sensitivity to 92.5% and specificity to 62.1%. There were positive significant correlations between SCCA-IgM and each of AFU (r=0.296, P=0.005) and AFP (r=0.284, P=0.007) and no correlation between AFP and AFU. All markers did not correlate with the tumor size or affected by the Child score. The significant difference between SCCA-IgM and AFU levels among HCC and cirrhotic patients suggests their use as potential diagnostic tools and allows identifying a new group of HCC patients even in the absence of elevated AFP.
Subject(s)
Antigens, Neoplasm/blood , Biomarkers, Tumor/blood , Carcinoma, Hepatocellular/diagnosis , Immunoglobulin M/blood , Liver Cirrhosis/diagnosis , Liver Neoplasms/diagnosis , Serpins/blood , alpha-L-Fucosidase/blood , Adult , Carcinoma, Hepatocellular/blood , Case-Control Studies , Enzyme-Linked Immunosorbent Assay , Female , Follow-Up Studies , Humans , Liver/metabolism , Liver/pathology , Liver Cirrhosis/blood , Liver Neoplasms/blood , Male , Middle Aged , Neoplasm Staging , Prognosis , ROC Curve , alpha-Fetoproteins/metabolismABSTRACT
BACKGROUND: Preoperative alpha-L-fucosidase (AFU) has been used as a diagnostic biomarker for hepatocellular carcinoma (HCC), but its role as a prognostic predictor after partial hepatectomy has not been well defined. The study aimed to investigate the prognostic significance of preoperative serum AFU for HCC patients after hepatic resection. METHODS: A retrospective training data set and a prospective validation data set were used to evaluate the prognosis of HCC after partial hepatectomy. A total of 669 patients with histopathologically confirmed HCC were enrolled. Univariate and multivariate analyses were used to identify the prognostic significance of preoperative serum AFU. RESULTS: The retrospective training data set showed a preoperative AFU>35 u l(-1) should be used. The prospective validation data set showed preoperative AFU was an independent prognostic factor of overall survival (OS) (P=0.008; hazard ratio: 2.333; 95% confidence interval: 1.249-4.369). Patients with a preoperative AFU>35 u l(-1) had a lower recurrence-free survival rate and an OS rate than those with AFU≤35 u l(-1), and they have a higher tendency to form macrovascular invasion. Furthermore, the prognostic significance of AFU>35 u l(-1) could also be applied to patients with alpha-fetoprotein levels of ≤400 ng ml(-1). CONCLUSIONS: Preoperative serum AFU is a prognostic predictor of HCC.
Subject(s)
Biomarkers, Tumor/blood , Carcinoma, Hepatocellular/diagnosis , Liver Neoplasms/diagnosis , alpha-L-Fucosidase/physiology , Adult , Aged , Carcinoma, Hepatocellular/blood , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/surgery , Female , Follow-Up Studies , Hepatectomy , Humans , Liver Neoplasms/blood , Liver Neoplasms/mortality , Liver Neoplasms/surgery , Male , Middle Aged , Prognosis , Retrospective Studies , Sample Size , Survival Analysis , Treatment Outcome , Validation Studies as Topic , alpha-L-Fucosidase/bloodABSTRACT
Alpha-fetoprotein (AFP) is the primary marker for detecting hepatocellular carcinoma (HCC) and has been used widely in the clinic, but AFP is a biomarker characterized by poor sensitivity and specificity. Alpha-L-fucosidase (AFU) has been proposed as a tumor marker for diagnosis of HCC in many studies. However, conclusions of its diagnostic value are inconsistent. The current review aimed to evaluate the diagnostic value of AFU for HCC. After systematic review of 12 related studies, sensitivity, specificity, and diagnostic odds ratio (DOR) were pooled using random-effect models. Summary receiver operating characteristic (sROC) curve analysis was used to summarize the overall test performance. The pooled sensitivity for AFU was 0.72 (95% confidence interval (CI) 0.69-0.76), while the pooled specificity was 0.78 (95% CI 0.74-0.81). DOR was 10.26 (95% CI 5.99-17.59), and the area under the curve (AUC) was 0.8125. AFU had great value for the diagnosis of HCC as a serum marker.
Subject(s)
Biomarkers, Tumor/blood , Carcinoma, Hepatocellular/diagnosis , Liver Neoplasms/diagnosis , alpha-L-Fucosidase/blood , Carcinoma, Hepatocellular/enzymology , Humans , Liver Neoplasms/enzymology , ROC CurveABSTRACT
BACKGROUND: In hospital patients suffering from adverse clinical and biochemical symptoms of malnutrition, it is often necessary to employ parenteral nutrition to avoid the body's tissue becoming broken down by being metabolised. Thus, the patient's welfare and survival can be supported throughout any periods of medical crisis. Two of the enzymes responsible for metabolising glycoconjugates are alpha-fucosidase (FUC) and beta-glucuronidase (GLU), present in lysosomes. They release fucose or glucuronic acid from the non-reducing end of oligosaccharide chains. OBJECTIVE: To determine the effect of parenteral nutrition administered to ill patients, on glycoconjugate metabolism, by measuring serum and urinary activities of FUC and GLU. Material and methods. Blood samples and the daily urine collection were taken from 23 patients' who had been undergoing parenteral nutrition for either 5 or 10 days, as well as from a baseline sample. Enzyme activities in serum and urine were determined by the method of Zwierz et al. RESULTS: Serum FUC activities were significantly lower after 10 days compared to 5, (p< 0.0172), whereas GLU activities were significantly lower after both 5 and 10 days, (p< 0.0007 and p< 0.0208 respectively), compared to levels before starting parenteral nutrition. GLU activities were however higher after 10 days than those after 5 days, (p< 0.0023). In urine, FUC activities were significantly decreased after 10 days compared to 5 days after starting parenteral nutrition, (p< 0.0245). Urine GLU activities were unaffected by parenteral nutrition nor was any effect seen on FUC or GLU activities when calculated per 1mg creatinine. CONCLUSIONS: Serum FUC and GLU activities can be used for assessing the effect of parenteral nutrition on glycoconjugate metabolism. The significant decreases of serum GLU activity observed after 5 and 10 days, may serve to indicate that the components of parental nutrition are appropriate and that the body has become suitably adapted to this form of nutrition.