Prognostic and immunological role of alpha-L-fucosidase 2 (FUCA2) in hepatocellular carcinoma.

Background: This study investigated the prognostic and immunological significance of alpha-L-fucosidase 2 (FUCA2) in hepatocellular cancer (HCC). Methods: The expression of FUCA2 and its clinical and prognostic values were explored across several databases, namely the University of Alabama Cancer Database, The Cancer Genome Atlas, Gene Expression Profiling Interactive Analysis, and the Human Protein Atlas. The prognostic relevance of FUCA2 was investigated using Kaplan-Meier curves, nomograms, and Cox analysis. The "limma" package in R was used to identify differentially expressed genes between high and low FUCA2 expression. A protein interaction network was established using the Search Tool for the Retrieval of Interacting Genes (STRING), whereas hub genes and clustering modules were identified using Cytoscape. "clusterProfiler", an R package, was used to examine the potential function of FUCA2. Using gene set enrichment analysis, signaling pathways associated with FUCA2 expression were identified. Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT), Tumor Immune Estimation Resource (TIMER) 2.0, and Tumor and Immune System Interaction Database (TISIDB) were used to examine immune infiltration and FUCA2 in HCC. Results: Many datasets indicated that FUCA2 expression is higher in HCC, and that this is related to age and overall survival (OS). With the cutoff value of 50% as the dividing threshold, the patients were divided into a high-FUCA2 expression group (n=167) and a low-FUCA2 expression group (n=168). High levels of FUCA2 expression coincided with decreased OS. FUCA2 expression in HCC was associated with immune infiltrates. The functional mechanisms of FUCA2 depend on signal release, extracellular matrix collagen, and neuroactive ligands and receptors. Conclusions: In HCC, increased FUCA2 expression is associated with a poor prognosis and immune infiltration. FUCA2 may serve as an immunological and predictive biomarker for HCC.

Association and prognostic significance of alpha-L-fucosidase-1 and matrix metalloproteinase 9 expression in esophageal squamous cell carcinoma.

BACKGROUND: Alpha-L-fucosidase-1 (FUCA1) has been demonstrated to play opposing regulatory roles in adenocarcinoma and non-adenocarcinoma. Moreover, recent studies reported that FUCA1 could decrease the invasion capability by downregulating matrix metalloproteinase 9 (MMP-9) expression. However, the potential role and prognostic significance of FUCA1 in esophageal squamous cell carcinoma (ESCC) have not yet been explored. AIM: To evaluate the status, association, and prognostic value of FUCA1 and MMP-9 expression in ESCC. METHODS: Patients who underwent esophagectomy for ESCC between January 1, 2014, and December 31, 2014 at Sun Yat-Sen University Cancer Center were enrolled. The expression status of FUCA1 and MMP-9 in cancerous tissues was detected using immunohistochemistry. In addition, the expression profiles of the FUCA1 and MMP-9 genes in non-metastatic ESCC were extracted from The Cancer Genome Atlas (TCGA) database. RESULTS: High expression of FUCA1 and MMP-9 was found in 90 patients (75.6%) and 62 patients (52.1%), respectively. In the high FUCA1 expression group, the constituent ratios of patients with stage III disease (61.1% vs 37.9%, P = 0.029), lymphatic invasion (62.2% vs 31.0%, P = 0.003), and high MMP-9 expression (60.0% vs 27.6%, P = 0.002) were significantly higher than those in the low FUCA1 expression group. In Kaplan-Meier univariate analysis, advanced tumor-node-metastasis stage (III, P = 0.001), positive regional lymph node metastasis (N+, P = 0.002), high FUCA1 expression (P = 0.001), and high MMP-9 expression (P = 0.002) were potential predictors of shorter overall survival (OS), which was similar to the results analyzed based on the TCGA database. Further Cox multivariate regression analyses still demonstrated that FUCA1 and MMP-9 expression levels were independent prognostic factors of OS [hazard ratio (HR): 0.484, 95% confidence interval (CI): 0.239-0.979; P = 0.044; and HR: 0.591, 95%CI: 0.359-0.973, P = 0.039, respectively]. CONCLUSION: FUCA1 cooperation with MMP-9 may have a major role in affecting the ESCC invasion and metastatic capability, and serve as a valuable prognostic biomarker in ESCC.

Alpha-L-fucosidase levels in patients with oral submucous fibrosis and controls: A comparative study.

Background: Oral submucous fibrosis (OSMF) in recent times has been recognized as a potentially malignant disorder (PMD) with an increased risk of developing oral squamous cell carcinoma with malignant transformation rates that vary from 0.6% to 36%. Alpha-L-fucosidase (AFU) is a lysosomal enzyme that is involved in maintaining the homeostasis of fucose metabolism. In benign and malignant tumors, the cells modulate their surface by increasing fucosylation leading to uncontrolled growth. Aims and objectives: This study was designed to estimate the levels of salivary and serum AFU in patients with OSMF and healthy controls and also to evaluate the clinical utility of salivary AFU levels over serum. Materials and Methods: Saliva and blood samples were collected from twenty participants in both the groups (OSMF and healthy controls). Serum and salivary alpha-L-fucosidase levels were measured by enzyme-linked immunosorbent assay. The data were subjected to appropriate statistical analysis. Results: We found a significant increase in alpha-L-fucosidase level in OSMF compared with healthy subjects. Pearson's correlation showed salivary alpha-L-fucosidase level to have superior sensitivity in detecting OSMF compared with serum alpha-L-fucosidase. Conclusion: The outcome of this study suggests that salivary alpha-L-fucosidase can be utilized as a biomarker in early detection of oral precancer and cancer.

Fucosidosis in Tunisian patients: mutational analysis and homology-based modeling of FUCA1 enzyme.

BACKGROUND: Fucosidosis is an autosomal recessive lysosomal storage disease caused by defective alpha-L-fucosidase (FUCA1) activity, leading to the accumulation of fucose-containing glycolipids and glycoproteins in various tissues. Clinical features include angiokeratoma, progressive psychomotor retardation, neurologic signs, coarse facial features, and dysostosis multiplex. METHODS: All exons and flanking intron regions of FUCA1 were screened by direct sequencing to identify mutations and polymorphisms in three unrelated families with fucosidosis. Bioinformatics tools were then used to predict the impacts of novel alterations on the structure and function of proteins. Furthermore, the identified mutations were localized onto a 3D structure model using the DeepView Swiss-PdbViewer 4.1 software, which established a function-structure relationship of the FUCA1 proteins. RESULTS: Four novel mutations were identified in this study. Two patients (P1 and P2) in Families 1 and 2 who had the severe phenotype were homoallelic for the two identified frameshift mutations p.K57Sfs*75 and p.F77Sfs*55, respectively. The affected patient (P3) from Family 3, who had the milder phenotype, was heterozygous for the novel missense mutation p.G332E and the novel splice site mutation c.662+5g>c. We verified that this sequence variation did not correspond to a polymorphism by testing 50 unrelated individuals. Additionally, 16 FUCA1 polymorphisms were identified. The structure prediction analysis showed that the missense mutation p.G332E would probably lead to a significant conformational change, thereby preventing the expression of the FUCA1 protein indeed; the 3D structural model of the FUCA1 protein reveals that the glycine at position 332 is located near a catalytic nucleophilic residue. This makes it likely that the enzymatic function of the protein with p.G332E is severely impaired. CONCLUSION: These are the first FUCA1 mutations identified in Tunisia that cause the fucosidosis disease. Bioinformatics analysis allowed us to establish an approximate structure-function relationship for the FUCA1 protein, thereby providing better genotype/phenotype correlation knowledge.

Unique Microbial Catabolic Pathway for the Human Core N-Glycan Constituent Fucosyl-α-1,6-N-Acetylglucosamine-Asparagine.

The survival of commensal bacteria in the human gut partially depends on their ability to metabolize host-derived molecules. The use of the glycosidic moiety of N-glycoproteins by bacteria has been reported, but the role of N-glycopeptides or glycoamino acids as the substrates for bacterial growth has not been evaluated. We have identified in Lactobacillus casei strain BL23 a gene cluster (alf-2) involved in the catabolism of the glycoamino acid fucosyl-α-1,6-N-GlcNAc-Asn (6'FN-Asn), a constituent of the core-fucosylated structures of mammalian N-glycoproteins. The cluster consists of the genes alfHC, encoding a major facilitator superfamily (MFS) permease and the α-l-fucosidase AlfC, and the divergently oriented asdA (aspartate 4-decarboxylase), alfR2 (transcriptional regulator), pepV (peptidase), asnA2 (glycosyl-asparaginase), and sugK (sugar kinase) genes. Knockout mutants showed that alfH, alfC, asdA, asnA2, and sugK are necessary for efficient 6'FN-Asn utilization. The alf-2 genes are induced by 6'FN-Asn, but not by its glycan moiety, via the AlfR2 regulator. The constitutive expression of alf-2 genes in an alfR2 strain allowed the metabolism of a variety of 6'-fucosyl-glycans. However, GlcNAc-Asn did not support growth in this mutant background, indicating that the presence of a 6'-fucose moiety is crucial for substrate transport via AlfH. Within bacteria, 6'FN-Asn is defucosylated by AlfC, generating GlcNAc-Asn. This glycoamino acid is processed by the glycosylasparaginase AsnA2. GlcNAc-Asn hydrolysis generates aspartate and GlcNAc, which is used as a fermentable source by L.casei These data establish the existence in a commensal bacterial species of an exclusive metabolic pathway likely to scavenge human milk and mucosal fucosylated N-glycopeptides in the gastrointestinal tract.IMPORTANCE The gastrointestinal tract accommodates more than 1014 microorganisms that have an enormous impact on human health. The mechanisms enabling commensal bacteria and administered probiotics to colonize the gut remain largely unknown. The ability to utilize host-derived carbon and energy resources available at the mucosal surfaces may provide these bacteria with a competitive advantage in the gut. Here, we have identified in the commensal species Lactobacillus casei a novel metabolic pathway for the utilization of the glycoamino acid fucosyl-α-1,6-N-GlcNAc-Asn, which is present in the core-fucosylated N-glycoproteins from mammalians. These results give insight into the molecular interactions between the host and commensal/probiotic bacteria and may help to devise new strategies to restore gut microbiota homeostasis in diseases associated with dysbiotic microbiota.

Alpha-l-fucosidase: a novel serum biomarker to predict prognosis in early stage esophageal squamous cell carcinoma.

BACKGROUND: Alpha-l-fucosidase (AFU) not only detects hepatocellular carcinoma (HCC) early but also is used as a clinical prognostic indicator of several malignant tumors. However, no study has investigated the prognostic significance of AFU in a cohort of patients with esophageal squamous cell carcinomas (ESCCs). METHODS: A retrospective dataset that included 160 consecutive patients with early stage (pT1N0) ESCC who received surgery between January 2005 and December 2012 was analyzed to identify the prognostic value of serum AFU for overall survival (OS) by using Kaplan-Meier analysis and Cox multivariate regression modeling. RESULTS: The level of serum AFU ranged from 6.2 to 77.0 U/L with a median of 19.9 U/L, and the best cutoff point for OS was 17.95 U/L. Analysis by Pearson's correlation showed that the levels of serum ALT and GGT were both positively correlated with the level of serum AFU (r=0.403, P<0.001 and r=0.264, P=0.001, respectively). After adjusting for significant factors identified by univariate analysis, the Cox multivariate regression model indicated that a young age (<65 years), no history of alcohol consumption, and a low AFU level (≤17.95 U/L) were still significantly associated with longer OS (P=0.008, 0.004 and 0.017, respectively). The 5-year and 10-year OS rates for patients with high AFU levels vs. low AFU levels were 76.2% vs. 86.0%, and, 46.7% vs. 83.4%, respectively. CONCLUSIONS: Compared with other serum biomarkers, AFU showed a better prognostic value for long-term survival in patients with early stage ESCC.

Alpha-L-fucosidase-1 is a diagnostic marker that distinguishes mucoepidermoid carcinoma from squamous cell carcinoma.

Alpha-L-fucose is a component of glycans on the cell surface. Alpha-L-fucose is correlated with tumorigenesis and malignancy, and alpha-L-fucosidase-1 (FUCA1), the enzyme that removes terminal α-L-fucose residues from glycoproteins, is downregulated in some high malignancy cancers. The expression profile of FUCA1 in head and neck tumors remains unknown, and we analyzed the expression profiles of FUCA1 and an upstream molecule p53 in mucoepidermoid carcinoma (MEC) and oral squamous cell carcinoma (OSCC). FUCA1 was expressed in most MECs irrespective of histopathological grading, whereas expression in OSCCs was low. High immunohistochemical intensity of p53 was detected in OSCCs at high frequency, but rarely detected in MECs. Genetic mutation analysis using next-generation sequencing revealed no significant mutation of TP53 in MECs. We further analyzed the expression profiles of FUCA1 in normal major and minor salivary glands and found strong expression in the intercalated duct, moderate expression in mucous acinar cells and no expression in serous acinar cells. These contrasting immunohistochemical profiles and anatomical distribution in normal salivary glands suggest that FUCA1 is a useful marker to distinguish MEC from OSCC, and many MECs have similar immunohistochemical phenotypes to intercalated duct and mucous acinar cells.

Diagnostic value of multiple serum tumor markers for hepatocellular carcinoma / 中国综合临床

Objective To explore the four tumor markers of alpha-fetoprotein ( AFP ), α-L-fucosidase( AFU), carbohydrate antigen 199 ( CA199) and carcinoembryonic antigen ( CEA) and their combined use for primary hepatocellular carcinoma (HCC) diagnosis and treatment value. Methods From February 2016 to August 2018,92 patients with primary hepatocellular carcinoma (HCC group),79 patients with benign liver disease (chronic hepatitis and cirrhosis group) and 99 healthy adults (control group) were selected as subjects. The serum levels of four tumor markers in different populations were compared. Results The serum levels of four tumor markers ( AFP ( 192. 4 ± 89. 3) μg／L、AFU( 78. 6 ± 25. 8) U／L、CA199 (107. 2 ± 59. 5) U／mL、 CEA ( 37. 9 ± 14. 9) μg／L) were significantly higher than those of benign liver disease group(AFP( 17. 4 ± 6. 3) μg／L、AFU( 35. 4 ± 17. 2) U／L、CA199( 29. 3± 15. 2) U／mL、CEA( 4. 9 ±1. 7) μg／L) and normal people( AFP(4. 8±1. 1) μg／L、AFU(12. 2±3. 6) U／L、CA199( 6. 4± 2. 3) U／mL、CEA(1. 8±0. 4) μg／L) . There differences had significant ( all P＜0. 05) . The abnormal rate of single factor in hepatocellular carcinoma group ( AFP 84. 8%, AFU 52. 2%, CA199 41. 3%, CEA35. 9%) was significantly higher than that in benign liver disease group ( AFP 15. 2%, AFU 19. 0%, CA19916. 5%, CEA13. 9%) and normal group (AFP 4. 0%,AFU 5. 0%,CA199 3. 0%,CEA 6. 0% ug／L),the difference was statistically significant ( all P＜0. 05) . The highest sensitivity was AFP ( 84. 8%) and the highest specificity was AFP and CA199 (91. 0%). The sensitivity of combined detection was 94. 6% higher than that of single index ( AFP 84. 8%, AFU52. 2%, CA199 41. 3%, CEA35. 9%) . Conclusion The combined detection of AFP,AFU,CA199 and CEA can increase the sensitivity of diagnosis of hepatocellular carcinoma and reduce the rate of missed diagnosis, which will be beneficial to the early diagnosis and treatment of hepatocellular carcinoma.

Carbon dots and gold nanoparticles based immunoassay for detection of alpha-L-fucosidase.

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 3.4 nM (well below the diagnostic cutoff point of 80 nM), and a broad linear range of detection from 11.3 to 200 nM were achieved. We also demonstrate the determination of the concentration of AFU in human blood serum.

Transcriptomic analysis of FUCA1 knock-down in keratinocytes reveals new insights into the pathogenesis of fucosidosis skin lesions.

Fucosidosis is a rare lysosomal storage disease which has been classified into two subtypes, depending on the severity of clinical signs and symptoms. Fucosidosis patients' skin abnormalities include angiokeratoma corporis diffusum, widespread telangiectasia, thick skin, hyperhidrosis and hypohidrosis, acrocyanosis and distal transverse nail bands. It has been described that >50% of fucosidosis patients have angiokeratoma. At molecular level, fucosidosis is caused by lysosomal alpha-L-fucosidase (FUCA1) gene mutations. Obtaining samples for functional studies has been challenging due to the inherent difficulty in finding affected individuals. The effect of FUCA1 dysfunction on gene expression is unknown. The aim of this study was to analyse, in keratinocytes, the transcriptomic effect of FUCA1 knock-down for a better understanding of skin lesions' pathogenesis affecting fucosidosis patients. FUCA1 knock-down (siRNA) was performed in human HaCaT immortalised keratinocytes. Affymetrix arrays and qPCR were used for analysing gene expression. Bioinformatics was used for functional clustering of modified genes. In total, 387 genes showed differential expression between FUCA1 silenced and non-silenced cells (222 up-regulated and 165 down-regulated). Up-regulated genes belonged to two major groups: keratinocyte differentiation/epidermal development (n = 17) and immune response (n = 61). Several transcription factors were up-regulated in FUCA1-siRNA transfected cells. This effect might partly have been produced by abnormal transcription factor expression, that is FOXN1. We thus propose that fucosidosis-related skin lesions (eg angiokeratoma) and those of other diseases (eg psoriasis) might be caused by dysfunctions in common aetiological overlapping molecular cascades.

Plasma alpha-L-fucosidase activity in chronic inflammation and autoimmune disorders in a pediatric cohort of hospitalized patients.

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.

The detection value of serum alpha -L -fucosidase and alpha fetoprotein 3 in primary hepatocellular ;carcinoma / 中国基层医药

Objective To study the detection value of serum alpha -L -fucosidase(AFU)and alpha fetoprotein 3(AFP -L3)in primary hepatocellular carcinoma(HCC).Methods 100 patients with primary HCC were enrolled as HCC group,54 cases without HCC were selected as non HCC group,100 healthy persons were selected as healthy group.Serum AFU and AFP-L3 levels in three groups were determined.The serum AFU was measured by the chemical colorimetry,and the AFP-L3 level was determined by chemiluminescence immunoassay.Results The serum levels of AFU in HCC group,non HCC group and healthy group were (71.61 ±3.01)U/L,(11.06 ±2.15)U/L, (8.54 ±1.28)U/L.The serum levels of AFP-L3 in HCC group,non HCC group and healthy group were (30.14 ± 2.93)%,(3.27 ±0.83)%,(2.77 ±0.62)%.The serum levels of AFU and AFP-L3 in HCC group were signifi-cantly higher than those in non HCC group and healthy group (t=13.172,9.770,16.036,7.160,all P0.05).The positive rates of AFU were 87.00%,9.26%and 3.00%in HCC group, non HCC group and healthy group.The positive rate of AFU in HCC group was significantly higher than that in non HCC group and healthy group (χ2 =34.06,57.62,all P0.05).The positive rates of AFP-L3 were 89.00%,7.41%and 2.00%in HCC group,non HCC group and healthy group.The positive rate of AFP-L3 in HCC group was significantly higher than that in non HCC group and healthy group (χ2 =41.06,77.62,all P0.05 ).There were no significant differences in serum tumor diameter about AFU, AFP-L3(t=0.167,0.579,0.201,0.601,all P>0.05),and there were significant differences about TNM stage, lymph node metastasis,and tumor thrombus (t =6.156,9.105,10.161,8.120,9.770,12.821,all P<0.05). Conclusion Serum AFU and AFP -L3 can not only help the diagnosis of primary liver cancer,but also can determine the prognosis of patients.

A correlated study between-L-alpha glucosidase and intrauterine growth and glucose and lipid metabolism in fetus below the gestational age / 实用医学杂志

Objective To investigate the change of serum alpha-L-fucosidase(AFU)and its correlation with the blood glucose and lipid level in small for gestational age(SGA)fetuses. Methods 125 SGA fetuses and 128 fetuses in appropriate for gestational age(AGA)with wet lung were treated in our hospital and were investigated as case control study. The serum of AFU ,blood glucose and lipid were measured and compared within 24 hours after birth in these 2 groups. Results Comparing with the AGA infants ,the SGA babies had lower level of serum AFU,high density lipoprotein,apolipoprotein A and apolipoprotein B(P<0.05). The correlation analysis showed that the serum AFU level has positive correlation with blood glucose,total cholesterol,high density lipoprotein, low density lipoproteinand apolipoprotein A(P < 0.05),while it has negative correlation with serum triglycerides in SGA(P<0.05). Conclusions The SGA infants have lower level of serum AFU and lipid metabolic disorders after birth,and its serum AFU level has correlation with its blood glucose and lipid level.

Assessment of serum GP73, AFP-L3, AFP and AFU detection in the diagnosis of hepatocellular carcinoma / 中华检验医学杂志

Objective Explore the clinical application values of Golgi Protein 73 ( GP73 ) , AFP variants (AFP-L3) , Alpha fetoprotein ( AFP) and α-l-Fucosidase ( AFU) detection in the diagnosis of hepatocellular carcinoma ( HCC) .Methods From January of 2013 to June of 2014, 84 case of HCC Patients( HCC group ) who presented at interventional department; 64 case of cirrhotic patients ( liver cirrhosis group ) , 86 case of chronic hepatitis patients ( chronic hepatitis group ) and 120 healthy people ( normal control group) were selected from Shanghai Tongren Hospital.GP73 was detected by the enzyme-linked immunosorbent assay (ELISA), AFP-L3 was isolated with ACSC, AFP and AFP-L3 were detected with ECLIA and calculated the percentage content of AFP-L3 ( AFP-L3%) , AFU was detected with enzyme kinetic method.Adopted the SPSS 19.0 statistical software for data analysis.The rank sum test was used in the multi group comparison;the chi square test was used in the comparison group.Results Serum levels of GP73, AFP-L3, AFP and AFU in HCC group were 202.1 μg/L, 9.5%, 68.3 μg/L, 33.2 μg/L respectively.Their difference from those of the normal control group(69.0 μg/L,2.5%,4.5 μg/L,24.2μg/L) was of statistical significance (U was 1126.59, 204.67,1247.68,564.08,respectively,all P 0.05) Sensitivity of GP73 and AFP in individual inspection was 95.24%, significantly higher than that of AFU, AFP-L3. Specificity of AFP-L3 was 94.81%respectively, with an accuracy of 85.88% respectively.Specificity and accuracy of the allied detection of GP73, AFP-L3, AFP and AFU for HCC diagnosis were 98.52% and 84.75% respectively.Conclusions The allied combination of serum GP73, AFP-L3, AFP and AFU makes up for the insufficient clinical applications of individual serum markers. It is of great clinical significance to improve the diagnosis of HCC.

Evaluation of the diagnostic value of alpha-l-fucosidase, alpha-fetoprotein and thymidine kinase 1 with ROC and logistic regression for hepatocellular carcinoma.

The purpose of this study was to evaluate the diagnostic efficiency for hepatocellular carcinoma (HCC) with the combined analysis of alpha-l-fucosidase (AFU), alpha-fetoprotein (AFP) and thymidine kinase 1 (TK1). Serum levels of AFU, AFP and TK1 were measured in: 116 patients with HCC, 109 patients with benign hepatic diseases, and 104 normal subjects. The diagnostic value was analyzed using the logistic regression equation and receiver operating characteristic curves (ROC). Statistical distribution of the three tested tumor markers in every group was non-normally distributed (Kolmogorov-Sminov test, Z = 0.156-0.517, P < 0.001). The serum levels of AFP and TK1 in patients with HCC were significantly higher than those in patients with benign hepatic diseases (Mann-Whitney U test, Z = -8.570 to -5.943, all P < 0.001). However, there was no statistically significant difference of AFU between these two groups (Mann-Whitney U test, Z = -1.820, P = 0.069). The levels of AFU were significantly higher in patients with benign hepatic diseases than in normal subjects (Mann-Whitney U test, Z = -7.984, P < 0.001). Receiver operating characteristic curves (ROC) in patients with HCC versus those without HCC indicated the optimal cut-off value was 40.80 U/L for AFU, 10.86 µg/L for AFP and 1.92 pmol/L for TK1, respectively. The area under ROC curve (AUC) was 0.718 for AFU, 0.832 for AFP, 0.773 for TK1 and 0.900 for the combination of the three tumor markers. The combination resulted in a higher Youden index and a sensitivity of 85.3%. The combined detection of serum AFU, AFP and TK1 could play a complementary role in the diagnosis of HCC, and could significantly improve the sensitivity for the diagnosis of HCC.

Application of serum alpha-L-fucosidase in monitoring the function of placenta / 国际检验医学杂志

Objective To investigate the application of maternal serum α-L-fucosidase to the placental function monitoring. Methods Comparative analysis of the changes of serum α-L-fucosidase between 120 patients with advanced placental dysfunction, pregnant women with different stages of gestation and 80 healthy non-pregnant woman was performed,and the correlation of the se-rum α-L-fucosidase of 120 cases with advanced placental dysfunction with UE3 and HPL was analyzed.Results The level of serumα-L-fucosidase of patients with placental dysfunction was lower than that of normal pregnant women,and the difference was statisti-cally significant (P <0.05 ).The serum α-L-fucosidase was correlated with UE3 and HPL which were the indicators of placental function monitoring (r=0.534 and 0.587,P <0.05).Conclusion Serum α-L-fucosidase can serve as the conventional biochemical indicator for monitoring placental function.

Study on correlation between the joint detection of CHE,AFU and AFP and primary liver cancer / 国际检验医学杂志

Objective To explore the correlation between the joint detection of cholinesterase(CHE),alpha-L-fucosidase(AFU) and alpha-fetoprotein(AFP)and primary hepatic cancer(PHC).Methods 56 cases of patients with PHC(PHC group),52 cases of patients with liver cirrhosis(LC group)and 60 cases of healthy individuals(control group)were enrolled in this study,and serum levels of CHE,AFU and AFP were detected and statistically analysed.Results Serum levels of CHE in patients with PHC were negatively correlated with levels of AFU and AFP(correlation coefficient was -0.889 and -0.797 respectively,P <0.05),the ser-um levels of CHE in patients with LC were also negatively correlated with levels of AFU and AFP (correlation coefficient was-0.598 and -0.653 respectively,P <0.05).The positive rates of joint detection of CHE,AFU and AFP in PHC group and LC group were higher than that in the control group,had statistically significant differences(P <0.05 ).Conclusion CHE,AFU and AFP are sensitive indicators of liver lesions,and the joint detection could provide reference value for diagnosis and monitoring pro-gression of PHC.

Carcinogenic effects of aflatoxin B1 among wheat handlers.

BACKGROUND: Epidemiological studies have demonstrated that serum aflatoxin B1 (AFB1) is a hepatocarcinogenic mycotoxin and contributor to the high rate of hepatocellular carcinoma (HCC). The prevalence of liver cancer in Egypt is particularly worrisome. In a registry-based analysis of occupational risk for HCC, significant excesses were observed especially for grain mill workers. OBJECTIVE: The aim of this study was to assess the hepatic carcinogenicity of AFB1 in wheat handlers. METHODS: Serum AFB1/albumin (AFB1/Alb), alpha-fetoprotein (AFP), alpha-l-fucosidase (AFU), and arginase were estimated in exposed wheat handlers including millers and bakers. The control group was composed of non-occupationally exposed workers. RESULTS: AFB1/Alb and AFU were significantly higher among workers employed as bakers compared to mill workers and controls. Mill workers had higher levels of AFB1/Alb than the controls. AFB1/Alb, AFP, and AFU were all significantly higher and arginase was significantly lower among HCC cases compared to the other groups. There was a significant correlation between AFU and AFB1/Alb in bakers and between AFP and AFB1/Alb in HCC cases. Arginase was inversely correlated with AFB1/Alb in HCC cases. AFB1/Alb was significantly correlated with the duration of exposure in bakers. CONCLUSION: Wheat handlers exposed to Aspergillus flavus have a high risk of elevated serum AFB1/Alb levels and AFU.