RESUMEN
Hepatocellular carcinoma (HCC) is the sixth common malignant tumor worldwide, but current efficient and convenient screening methods remain lacking. This study aimed to discover a diagnostic or a screening biomarker from the urine of hepatitis B virus (HBV)-related HCC patients. We used iTRAQ coupled with mass spectrometry to identify candidate urinary proteins in a discovery cohort (n = 40). The selected proteins were confirmed using ELISA in a validation cohort (n = 140). Diagnostic performance of the selected proteins was assessed using receiver operating characteristic (ROC) and qualitative diagnostic analysis. A total of 96 differentially expressed proteins were identified. Urinary α-fetoprotein (u-AFP) and orosomucoid 1 (u-ORM1) were selected as target proteins by bioinformatics analysis and were significantly higher in HCC than in non-HCC patients, as validated by Western blot analysis and ELISA. u-AFP had a strong correlation with serum AFP-L3 (Pearson's r = 0.944, P < 0.0001), indicating that u-AFP may be derived from circulating blood. The area under the curve (AUC) of u-AFP was 0.795 with a sensitivity of 62.5% and a specificity of 95.4%, which showed no significantly difference with serum AFP (se-AFP). The AUC was 0.864 as u-AFP and u-ORM1 were combined, and they performed much better than u-AFP or u-ORM1 alone. Qualitative diagnostic analysis showed that the positive predictive value of u-AFP was 90.1% and the diagnostic sensitivity of parallel combination of u-AFP and u-ORM1 was 85.1%. Taken together, AFP and ORM1 in the urine may be used as a diagnostic or screening biomarker of HCC, and studies on large samples are needed to validate the result.NEW & NOTEWORTHY This study provides a novel way to find biomarkers of hepatocellular carcinoma (HCC) and a new perspective of α-fetoprotein clinical application. The urine reagent strips may be helpful in high epidemic areas of HCC and in low-resource settings.
Asunto(s)
Biomarcadores/orina , Carcinoma Hepatocelular/etiología , Carcinoma Hepatocelular/orina , Virus de la Hepatitis B , Hepatitis B Crónica/complicaciones , Neoplasias Hepáticas/etiología , Neoplasias Hepáticas/orina , Orosomucoide/orina , alfa-Fetoproteínas/orina , Adulto , Anciano , Estudios de Cohortes , Femenino , Humanos , Masculino , Tamizaje Masivo , Persona de Mediana Edad , Proteoma , Reproducibilidad de los Resultados , alfa-Fetoproteínas/genéticaRESUMEN
BACKGROUND: Down's syndrome occurs when a person has three copies of chromosome 21, or the specific area of chromosome 21 implicated in causing Down's syndrome, rather than two. It is the commonest congenital cause of mental disability and also leads to numerous metabolic and structural problems. It can be life-threatening, or lead to considerable ill health, although some individuals have only mild problems and can lead relatively normal lives. Having a baby with Down's syndrome is likely to have a significant impact on family life. The risk of a Down's syndrome affected pregnancy increases with advancing maternal age.Noninvasive screening based on biochemical analysis of maternal serum or urine, or fetal ultrasound measurements, allows estimates of the risk of a pregnancy being affected and provides information to guide decisions about definitive testing. Before agreeing to screening tests, parents need to be fully informed about the risks, benefits and possible consequences of such a test. This includes subsequent choices for further tests they may face, and the implications of both false positive and false negative screening tests (i.e. invasive diagnostic testing, and the possibility that a miscarried fetus may be chromosomally normal). The decisions that may be faced by expectant parents inevitably engender a high level of anxiety at all stages of the screening process, and the outcomes of screening can be associated with considerable physical and psychological morbidity. No screening test can predict the severity of problems a person with Down's syndrome will have. OBJECTIVES: To estimate and compare the accuracy of first and second trimester urine markers for the detection of Down's syndrome. SEARCH METHODS: We carried out a sensitive and comprehensive literature search of MEDLINE (1980 to 25 August 2011), EMBASE (1980 to 25 August 2011), BIOSIS via EDINA (1985 to 25 August 2011), CINAHL via OVID (1982 to 25 August 2011), The Database of Abstracts of Reviews of Effectiveness (The Cochrane Library 2011, Issue 7), MEDION (25 August 2011), The Database of Systematic Reviews and Meta-Analyses in Laboratory Medicine (25 August 2011), The National Research Register (archived 2007), Health Services Research Projects in Progress database (25 August 2011). We studied reference lists and published review articles. SELECTION CRITERIA: Studies evaluating tests of maternal urine in women up to 24 weeks of gestation for Down's syndrome, compared with a reference standard, either chromosomal verification or macroscopic postnatal inspection. DATA COLLECTION AND ANALYSIS: We extracted data as test positive or test negative results for Down's and non-Down's pregnancies allowing estimation of detection rates (sensitivity) and false positive rates (1-specificity). We performed quality assessment according to QUADAS (Quality Assessment of Diagnostic Accuracy Studies) criteria. We used hierarchical summary ROC (receiver operating characteristic) meta-analytical methods to analyse test performance and compare test accuracy. We performed analysis of studies allowing direct comparison between tests. We investigated the impact of maternal age on test performance in subgroup analyses. MAIN RESULTS: We included 19 studies involving 18,013 pregnancies (including 527 with Down's syndrome). Studies were generally of high quality, although differential verification was common with invasive testing of only high-risk pregnancies. Twenty-four test combinations were evaluated formed from combinations of the following seven different markers with and without maternal age: AFP (alpha-fetoprotein), ITA (invasive trophoblast antigen), ß-core fragment, free ßhCG (beta human chorionic gonadotrophin), total hCG, oestriol, gonadotropin peptide and various marker ratios. The strategies evaluated included three double tests and seven single tests in combination with maternal age, and one triple test, two double tests and 11 single tests without maternal age. Twelve of the 19 studies only evaluated the performance of a single test strategy while the remaining seven evaluated at least two test strategies. Two marker combinations were evaluated in more than four studies; second trimester ß-core fragment (six studies), and second trimester ß-core fragment with maternal age (five studies).In direct test comparisons, for a 5% false positive rate (FPR), the diagnostic accuracy of the double marker second trimester ß-core fragment and oestriol with maternal age test combination was significantly better (ratio of diagnostic odds ratio (RDOR): 2.2 (95% confidence interval (CI) 1.1 to 4.5), P = 0.02) (summary sensitivity of 73% (CI 57 to 85) at a cut-point of 5% FPR) than that of the single marker test strategy of second trimester ß-core fragment and maternal age (summary sensitivity of 56% (CI 45 to 66) at a cut-point of 5% FPR), but was not significantly better (RDOR: 1.5 (0.8 to 2.8), P = 0.21) than that of the second trimester ß-core fragment to oestriol ratio and maternal age test strategy (summary sensitivity of 71% (CI 51 to 86) at a cut-point of 5% FPR). AUTHORS' CONCLUSIONS: Tests involving second trimester ß-core fragment and oestriol with maternal age are significantly more sensitive than the single marker second trimester ß-core fragment and maternal age, however, there were few studies. There is a paucity of evidence available to support the use of urine testing for Down's syndrome screening in clinical practice where alternatives are available.
Asunto(s)
Biomarcadores/orina , Síndrome de Down/diagnóstico , Primer Trimestre del Embarazo/orina , Segundo Trimestre del Embarazo/orina , Gonadotropina Coriónica/orina , Estriol/orina , Reacciones Falso Positivas , Femenino , Gonadotropinas/orina , Humanos , Edad Materna , Valor Predictivo de las Pruebas , Embarazo , Sensibilidad y Especificidad , alfa-Fetoproteínas/orinaRESUMEN
UNLABELLED: There is no clinically applicable biomarker for surveillance of hepatocellular carcinoma (HCC), because the sensitivity of serum alpha-fetoprotein (AFP) is too low for this purpose. Here, we determined the diagnostic performance of a panel of urinary metabolites of HCC patients from West Africa. Urine samples were collected from Nigerian and Gambian patients recruited on the case-control platform of the Prevention of Liver Fibrosis and Cancer in Africa (PROLIFICA) program. Urinary proton nuclear magnetic resonance ((1) H-NMR) spectroscopy was used to metabolically phenotype 290 subjects: 63 with HCC; 32 with cirrhosis (Cir); 107 with noncirrhotic liver disease (DC); and 88 normal control (NC) healthy volunteers. Urine samples from a further cohort of 463 subjects (141 HCC, 56 Cir, 178 DC, and 88 NC) were analyzed, the results of which validated the initial cohort. The urinary metabotype of patients with HCC was distinct from those with Cir, DC, and NC with areas under the receiver operating characteristic (AUROC) curves of 0.86 (0.78-0.94), 0.93 (0.89-0.97), and 0.89 (0.80-0.98) in the training set and 0.81 (0.73-0.89), 0.96 (0.94-0.99), and 0.90 (0.85-0.96), respectively, in the validation cohort. A urinary metabolite panel, comprising inosine, indole-3-acetate, galactose, and an N-acetylated amino acid (NAA), showed a high sensitivity (86.9% [75.8-94.2]) and specificity (90.3% [74.2-98.0]) in the discrimination of HCC from cirrhosis, a finding that was corroborated in a validation cohort (AUROC: urinary panel = 0.72; AFP = 0.58). Metabolites that were significantly increased in urine of HCC patients, and which correlated with clinical stage of HCC, were NAA, dimethylglycine, 1-methylnicotinamide, methionine, acetylcarnitine, 2-oxoglutarate, choline, and creatine. CONCLUSION: The urinary metabotyping of this West African cohort identified and validated a metabolite panel that diagnostically outperforms serum AFP.
Asunto(s)
Biomarcadores de Tumor/orina , Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/diagnóstico , Metionina/orina , Niacinamida/análogos & derivados , Sarcosina/análogos & derivados , alfa-Fetoproteínas/orina , Acetilcarnitina/orina , Adolescente , Adulto , África Occidental/epidemiología , Anciano , Anciano de 80 o más Años , Carcinoma Hepatocelular/epidemiología , Carcinoma Hepatocelular/orina , Estudios de Casos y Controles , Colina/orina , Creatina/orina , Femenino , Humanos , Ácidos Cetoglutáricos/orina , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/orina , Masculino , Persona de Mediana Edad , Niacinamida/orina , Fenotipo , Reproducibilidad de los Resultados , Sarcosina/orina , Sensibilidad y Especificidad , Adulto JovenRESUMEN
UNLABELLED: Sterigmatocystin (STC) is a wide spread mycotoxin produced by Aspergillus fungi, with hepatotoxic and carcinogenetic proprieties. OBJECTIVES: To determine the STC concentration in blood and urine from patient with liver cirrhosis (LC) and hepatocellular carcinoma (HCC), with correlation with liver function parameters. MATERIAL AND METHODS: The study enrolled 166 patients divided in three groups: control--55 patients (27M, 28F); LC--58 patients (31M, 27F); HCC--53 patients (26M, 27F). 20 ml of blood and 50 ml of urine were collected from each patient and liver enzymes and alfa-fetoprotein (AFP) were measured. STC was determined by high performance liquid chromatography, with concomitant detection in ultraviolet and fluorescence. RESULTS: STC was detected in 26.2% of samples, more frequently in LC and HCC groups (p < 0.001). STC mean values were 0.014 ng/ml and 0.005 ng/ml in blood, respective urine of controls, rising to 0.626 ng/ml (p = 0.003) respective 1.053 ng/ml (p = 0.049) in LC and 2.02 ng/ml in blood (p < 0.0001) and 9.39 ng/ml in urine (p = 0.003) in patients with HCC. There is a perfect correlation between serum and urinary levels of STC in controls (r = 1), that become weak in patients with LC (r = 0.48) and insignificant in HCC (r = 0.15). AFP values were significantly correlated with STC concentration in patient with HCC, in both blood (r = 0.31) and urine (r = 0.84). CONCLUSIONS: STC values in patients with LC and HCC were significantly higher compared to controls. Strong positive correlation of STC with AFP in patients with liver cancer suggested a possible role of this mycotoxin in pathogenesis of the disease.
Asunto(s)
Hepatopatías/sangre , Hepatopatías/orina , Esterigmatocistina/sangre , Esterigmatocistina/orina , Anciano , Biomarcadores/sangre , Biomarcadores/orina , Carcinoma Hepatocelular/sangre , Carcinoma Hepatocelular/orina , Estudios de Casos y Controles , Cromatografía Líquida de Alta Presión , Enfermedad Crónica , Femenino , Humanos , Cirrosis Hepática/sangre , Cirrosis Hepática/orina , Hepatopatías/diagnóstico , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/orina , Masculino , Persona de Mediana Edad , alfa-Fetoproteínas/metabolismo , alfa-Fetoproteínas/orinaRESUMEN
Hepatocellular carcinoma (HCC) is a common malignancy in the world with high morbidity and mortality rate. Identification of novel biomarkers in HCC remains impeded primarily because of the heterogeneity of the disease in clinical presentations as well as the pathophysiological variations derived from underlying conditions such as cirrhosis and steatohepatitis. The aim of this study is to search for potential metabolite biomarkers of human HCC using serum and urine metabolomics approach. Sera and urine samples were collected from patients with HCC (n = 82), benign liver tumor patients (n = 24), and healthy controls (n = 71). Metabolite profiling was performed by gas chromatography time-of-flight mass spectrometry and ultra performance liquid chromatography-quadrupole time of flight mass spectrometry in conjunction with univariate and multivariate statistical analyses. Forty three serum metabolites and 31 urinary metabolites were identified in HCC patients involving several key metabolic pathways such as bile acids, free fatty acids, glycolysis, urea cycle, and methionine metabolism. Differentially expressed metabolites in HCC subjects, such as bile acids, histidine, and inosine are of great statistical significance and high fold changes, which warrant further validation as potential biomarkers for HCC. However, alterations of several bile acids seem to be affected by the condition of liver cirrhosis and hepatitis. Quantitative measurement and comparison of seven bile acids among benign liver tumor patients with liver cirrhosis and hepatitis, HCC patients with liver cirrhosis and hepatitis, HCC patients without liver cirrhosis and hepatitis, and healthy controls revealed that the abnormal levels of glycochenodeoxycholic acid, glycocholic acid, taurocholic acid, and chenodeoxycholic acid are associated with liver cirrhosis and hepatitis. HCC patients with alpha fetoprotein values lower than 20 ng/ml was successfully differentiated from healthy controls with an accuracy of 100% using a panel of metabolite markers. Our work shows that metabolomic profiling approach is a promising screening tool for the diagnosis and stratification of HCC patients.
Asunto(s)
Biomarcadores de Tumor/sangre , Carcinoma Hepatocelular/sangre , Neoplasias Hepáticas/sangre , Metaboloma , Adolescente , Adulto , Anciano , Ácidos y Sales Biliares/sangre , Ácidos y Sales Biliares/orina , Biomarcadores de Tumor/orina , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/orina , Estudios de Casos y Controles , Femenino , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/orina , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Análisis de Componente Principal , Adulto Joven , alfa-Fetoproteínas/metabolismo , alfa-Fetoproteínas/orinaRESUMEN
OBJECTIVE: To investigate the relationship of urine fetuin-A and other promotors and inhibitors of urine crystalization with urolithiasis, as fetuin-A inhibits the precipitation of hydroxyapatite from supersaturated solutions of calcium and phosphate in vitro but no information on urine fetuin-A in patients with urolithiasis is available. PATIENTS AND METHODS: In all, 39 patients with urolithiasis and 22 individuals with no urolithiasis or probands with undetected stones were involved. All patients underwent kidney ultrasonography and X-ray examination, and body mass index (BMI) was calculated. Serum creatinine, parathyroid hormone, calcium, magnesium, anorganic phosphate, uric acid and urine creatinine, albumin, alpha(1)-microglobulin, sulphate, oxalate, citrate and fetuin-A (ELISA) were determined. RESULTS: The patients with urolithiasis had lower urine fetuin-A levels (median 4.9 vs 0.77 mg/day; P < 0.01) and citraturia levels (1.7 vs 5.1 mmol/day; P = 0.02); and higher calciuria (6.5 vs 5.2 mmol/day) and oxaluria (0.47 vs 0.25; P = 0.04). Patients with fetuin-A levels in the lowest quartile had an odds ratio of 36 compared with individuals in the highest quartile. The sensitivity of the urine fetuin-A level for urolithiasis was 97.4% and specificity was 100% (area under the curve 0.99; 95% confidence interval 0.94-1.0) using a urine fetuin-A threshold of Asunto(s)
Urolitiasis/patología
, alfa-Fetoproteínas/metabolismo
, Estudios de Casos y Controles
, Cristalización
, Ensayo de Inmunoadsorción Enzimática
, Femenino
, Humanos
, Masculino
, Persona de Mediana Edad
, Recurrencia
, Sensibilidad y Especificidad
, Urolitiasis/sangre
, Urolitiasis/orina
, alfa-Fetoproteínas/orina
RESUMEN
Urinary exosomes containing apical membrane and intracellular fluid are normally secreted into the urine from all nephron segments, and may carry protein markers of renal dysfunction and structural injury. We aimed to discover biomarkers in urinary exosomes to detect acute kidney injury (AKI), which has a high mortality and morbidity. Animals were injected with cisplatin. Urinary exosomes were isolated by differential centrifugation. Protein changes were evaluated by two-dimensional difference in gel electrophoresis and changed proteins were identified by mass spectrometry. The identified candidate biomarkers were validated by Western blotting in individual urine samples from rats subjected to cisplatin injection; bilateral ischemia and reperfusion (I/R); volume depletion; and intensive care unit (ICU) patients with and without AKI. We identified 18 proteins that were increased and nine proteins that were decreased 8 h after cisplatin injection. Most of the candidates could not be validated by Western blotting. However, exosomal Fetuin-A increased 52.5-fold at day 2 (1 day before serum creatinine increase and tubule damage) and remained elevated 51.5-fold at day 5 (peak renal injury) after cisplatin injection. By immunoelectron microscopy and elution studies, Fetuin-A was located inside urinary exosomes. Urinary Fetuin-A was increased 31.6-fold in the early phase (2-8 h) of I/R, but not in prerenal azotemia. Urinary exosomal Fetuin-A also increased in three ICU patients with AKI compared to the patients without AKI. We conclude that (1) proteomic analysis of urinary exosomes can provide biomarker candidates for the diagnosis of AKI and (2) urinary Fetuin-A might be a predictive biomarker of structural renal injury.
Asunto(s)
Lesión Renal Aguda/orina , Proteínas Sanguíneas/orina , Proteómica/métodos , Daño por Reperfusión/orina , Lesión Renal Aguda/etiología , Lesión Renal Aguda/patología , Adulto , Anciano , Anciano de 80 o más Años , Animales , Antineoplásicos/efectos adversos , Antineoplásicos/farmacología , Biomarcadores/orina , Membrana Celular/metabolismo , Cisplatino/efectos adversos , Cisplatino/farmacología , Femenino , Humanos , Riñón/efectos de los fármacos , Riñón/lesiones , Riñón/patología , Masculino , Persona de Mediana Edad , Modelos Animales , Ratas , Daño por Reperfusión/etiología , Daño por Reperfusión/patología , alfa-2-Glicoproteína-HS , alfa-Fetoproteínas/orinaRESUMEN
The tumor markers for malignant tumors arisen from urinary system including prostate cancer were reviewed. As for renal cell carcinoma there was no good marker used in routine test level at present. In the diagnosis of urothelial (transitional cell) carcinoma, mainly bladder cancer, 3 methods (urinary BTA, NMP22 and BFP) are used now in Japan. They all seem to be not fully sufficient in respect of the specificity. In foreign countries, new tests such as urinary telomerase and BLCA-4 are used and have been evaluated. On the diagnosis of prostate cancer, serum total PSA is well established and used. Various PSA relation markers have been advocated for the differentiation between benign prostate hypertrophy and carcinoma in so called "gray zone" level of total PSA. In methods based on the molecular forms of PSA, the ratio of free PSA to total PSA (f/T) is widely use, and proPSA is a test that is expected. Other approaches such as volume of index PSA, age specific PSA reference range and PSA velocity are also in practical application. Human glandular kallikrein 2, which belong to the human kallikrein family as well as PSA, is expected as a tumor specific marker.
Asunto(s)
Antígenos de Neoplasias/orina , Biomarcadores de Tumor/orina , Proteínas Nucleares/orina , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/diagnóstico , Neoplasias Urológicas/diagnóstico , Biomarcadores de Tumor/sangre , Ensayo de Inmunoadsorción Enzimática/métodos , Productos de Degradación de Fibrina-Fibrinógeno/orina , Humanos , Inmunohistoquímica/métodos , Masculino , Telomerasa , Calicreínas de Tejido/sangre , alfa-Fetoproteínas/orinaRESUMEN
BACKGROUND/AIM: N1,N12-diacetylspermine (DiAcSpm), a diacetylpolyamine which was recently identified in urine, appeared to be a useful tumor marker for urogenital cancers. Here we examined the clinical significance of urinary DiAcSpm as a tumor marker for hepatocellular carcinoma (HCC). METHODS: Urine samples were collected from patients with HCC and benign liver diseases. Urinary levels of DiAcSpm were measured by ELISA, which was newly developed in order to analyze large numbers of samples. RESULTS: The appropriate threshold value was set at 325 nM/g x creatinine. The sensitivity of the DiAcSpm assay for HCC was 65.5% and the specificity calculated between HCC and liver cirrhosis was 76.0%. The percentage of DiAcSpm-positive HCC patients was similar to that for AFP or PIVKA-II. At more advanced clinical stages, the positive percentage of these three markers increased but the DiAcSpm levels appeared to move independently of AFP and PIVKA-II. In HCC patients, the DiAcSpm levels reflected the progression of disease or the effect of treatment. CONCLUSIONS: DiAcSpm levels were found to reflect the severity, activity or viability of HCC. Urinary DiAcSpm can therefore be considered one of the useful indexes for patients with HCC.
Asunto(s)
Carcinoma Hepatocelular/orina , Neoplasias Hepáticas/orina , Espermina/análogos & derivados , Espermina/orina , Biomarcadores/orina , Biomarcadores de Tumor , Creatinina/metabolismo , Ensayo de Inmunoadsorción Enzimática , Reacciones Falso Positivas , Humanos , Hígado/metabolismo , Cirrosis Hepática/orina , Poliaminas/orina , Precursores de Proteínas/orina , Protrombina/orina , Curva ROC , Sensibilidad y Especificidad , Factores de Tiempo , alfa-Fetoproteínas/orinaRESUMEN
Alpha-fetoprotein (AFP) was 1 of the first serum protein markers to serve in the dual capacities of tumor marker and fetal defect marker, ie, an oncofetal protein, in the clinical laboratory. Although the serum-marker capacity of AFP has long been used, less is known of the fluid compartments of this oncofetal protein during fetal and perinatal development. In this review, the biologic activities of AFP are discussed in light of its presence in the various biologic fluid compartments: fetal serum, amniotic fluid, cord blood, urine, and maternal serum. AFP concentrations within the biologic fluids are considered in the context of gestational age, sex, body weight, and anatomic location. Discussion follows concerning the relationships and roles of AFP in various developmental disorders such as hypothyroidism, folate deficiencies, autoimmune disorders, acquired immunodeficiency disorder (AIDS), congenital heart defects, cystic fibrosis, preeclampsia/hypertension, and platelet aggregation disorders. Based on its presence in so many types of birth defects, malformations, and congenital anomalies, AFP can be seen to serve as a form of molecular "duct tape" during pregnancy and postnatal development.
Asunto(s)
Sangre Fetal/química , Intercambio Materno-Fetal , Complicaciones del Embarazo/diagnóstico , Diagnóstico Prenatal , alfa-Fetoproteínas/análisis , Síndrome de Inmunodeficiencia Adquirida/diagnóstico , Amniocentesis/métodos , Líquido Amniótico/química , Enfermedades Autoinmunes/diagnóstico , Anomalías Congénitas/sangre , Anomalías Congénitas/diagnóstico , Fibrosis Quística/diagnóstico , Diabetes Mellitus Tipo 1/diagnóstico , Eritropoyesis , Femenino , Deficiencia de Ácido Fólico/diagnóstico , Cardiopatías Congénitas/diagnóstico , Humanos , Hipotiroidismo/diagnóstico , Masculino , Agregación Plaquetaria , Preeclampsia/diagnóstico , Embarazo , alfa-Fetoproteínas/orinaRESUMEN
The urinary tumor markers BTA, BFP and NMP22 used for urothelial cancer in Japan are reviewed briefly. We also evaluate and compare the sensitivity and specificity of BTA, BFP and NMP22 with urine cytology in detecting bladder cancer in 24 of our patients. The results showed that the sensitivity with urine cytology, BTA, BFP and NMP22 was 37, 54, 66 and 62% respectively. The specificity of BTA, BFP and NMP22 with urine cytology was 100, 65, 60 and 70% respectively. The sensitivity with BTA, BFP and NMP22 for urothelial cancer was higher than that with urine cytology. However, all except for urine cytology showed high false positive rates (83-90%) for urinary tract infection. These markers may thus complement urine cytology, which has a low sensitivity for urothelial cancer. Quite possibly they could act as low-cost and useful tumor markers, which could in turn reduce the number of invasive cystoscopic examinations. However, considering their high false positive rates for benign disease such as urinary tract infection, we must acknowledge that an ideal urothelial tumor marker, which is simple, non-invasive, inexpensive and accurate with high sensitivity and specificity has yet to be developed.
Asunto(s)
Biomarcadores de Tumor/orina , Neoplasias de la Vejiga Urinaria/diagnóstico , Neoplasias Urológicas/diagnóstico , Antígenos de Neoplasias/orina , Humanos , Proteínas Nucleares/orina , Telomerasa/metabolismo , Neoplasias de la Vejiga Urinaria/orina , Orina/citología , Neoplasias Urológicas/orina , alfa-Fetoproteínas/orinaRESUMEN
BACKGROUND: The reliability of a new screening test for epithelial cancer of the urinary tract was evaluated and the results were compared with those obtained employing urinary cytology in routine use. METHODS: The subjects consisted of 187 cases selected randomly from among the patients who attended Toho University Ohashi Hospital during a period of 1 year from January 1998. The values for urine basic fetoprotein (BFP) and polyamine and urinary cytology were examined. RESULTS: Urine BFP is considered useful for screening and monitoring urinary tract epithelial cancer as is urinary cytology. Urine BFP showed a statistically significant difference (P < 0.05) for G1 compared with urinary cytology and a significantly high level compared with urinary cytology as to the positive rate in the low stage group (P < 0.05). The positive rate of urine BFP was high in patients with urinary tract infection. CONCLUSION: Determining urine BFP, when combined with urinary cytology, is considered very useful for diagnosing patients with urinary tract epithelial cancer. This study suggests the possibility of urine BFP being superior to urinary cytology for screening early cancer and also as an indicator for observations on the clinical course.
Asunto(s)
Biomarcadores de Tumor/orina , Carcinoma de Células Transicionales/orina , Poliaminas/orina , Neoplasias Urológicas/orina , alfa-Fetoproteínas/orina , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Orina/citologíaRESUMEN
PURPOSE: The early diagnosis of bladder cancer allows for effective local treatment and optimizes the success of surgical therapy. Basic fetoprotein (BFP), measured using a rapid latex immuno-agglutination method, was introduced for the detection of transitional cell carcinoma. The objective of this study was to determine whether there was a correlation between urine BFP level and the grade or stage of bladder cancer, and whether the level could serve as a biochemical marker of bladder cancer. MATERIALS AND METHODS: Single voided specimens were obtained from 66 patients with confirmed or suspicious bladder cancer on cystoscopy, urine cytology or BFP. Each sample was divided into 3 aliquots of which 1 was for urine analysis, 1 was tested for BFP according to latex immunoagglutination method and 1 was sent for cytological examination. All patients subsequently underwent bladder biopsy. RESULTS: There were 54 (82%) patients with biopsy confirmed bladder cancer and 12 (18%) with benign conditions of the bladder. Overall sensitivity with BFP and urine cytology was 38.9% and 48.1% respectively. Specificity was 58.3% and 75.0%, and positive predictive value was 80.8% and 89.7%, respectively. The positive rate of BFP and cytology was higher in invasive cancer (75% and 100%, respectively) than in superficial cancer (36% and 28%). There was no correlation between BFP level and tumor grade, while cytology had a strong association. Linear regression analysis showed the significant correlation between BFP level and tumor size (r = 0.695, p < 0.0001). The detection rate of bladder cancer was higher by the combination of BFP and cytology than by using alone. CONCLUSIONS: BFP in conjunction with urine cytology can increase the detection rate of bladder cancer. But BFP alone cannot be used as a screening test for bladder cancer.
Asunto(s)
Biomarcadores de Tumor/orina , Carcinoma de Células Transicionales/diagnóstico , Neoplasias de la Vejiga Urinaria/diagnóstico , alfa-Fetoproteínas/orina , Adulto , Anciano , Anciano de 80 o más Años , Citodiagnóstico , Humanos , Pruebas de Fijación de Látex , Persona de Mediana Edad , Sensibilidad y EspecificidadRESUMEN
We compared the results of urinary basic fetoprotein (BFP) and the BTA test with those of urinary cytology in patients with bladder cancer. We also analyzed the urinary BFP and the BTA test results in patients with benign diseases and postoperative bladder cancer with no evidence of recurrence. The cutoff value for urinary BFP was set at 10 ng/ml. Classes 4 and 5 according to urinary cytology were defined as positive. The sensitivity of urinary BFP for Ta, 1 bladder cancer was significantly higher than that of urinary cytology (p < 0.05). The urinary cytology positive rate for Ta, 1 bladder cancer improved when combined with urinary BFP and the BTA test. The urinary BFP positive rate for benign diseases was significantly higher in patients with pyuria than in patients without pyuria (p < 0.05). The BTA test positive rate for benign diseases was higher in patients with pyuria than in patients without pyuria. The urinary BFP and the BTA test positive rates for postoperative bladder cancer with no evidence of recurrence was significantly higher in patients with urinary diversion than in patients without urinary diversion (BFP: p < 0.01, BTA: p < 0.05).
Asunto(s)
Antígenos de Neoplasias/orina , Biomarcadores de Tumor/orina , Neoplasias de la Vejiga Urinaria/diagnóstico , alfa-Fetoproteínas/orina , Adulto , Anciano , Anciano de 80 o más Años , Citodiagnóstico , Reacciones Falso Positivas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: The aim of this study was to ascertain the normal range of the midtrimester maternal urine alpha-fetoprotein (AFP) concentrations in Taiwanese pregnancies. METHODS: AFP was measured in the urine samples, obtained before genetic amniocentesis, from 268 women with normal singleton pregnancies between 14 and 21 weeks of gestation. Week-specific median values for urine AFP/creatinine (Cr) were calculated by weighted linear regression after log transformation and the data were converted to units in the multiple of the median (MoM). The gestational age in all cases was determined by ultrasound parameters. RESULTS: The levels of urine AFP and AFP/Cr increased gradually with advancing gestational age. The AFP/Cr MoM values of singleton pregnancies after log transformation showed a normal distribution with a mean (standard deviation) of 0.0071 (0.3228). The median, 10th and 90th centiles of AFP/Cr were 0.98, 0.43 and 3.61 MoM, respectively. Of the pregnant Taiwanese women studied, 4.9% (13/268) and 16% (43/268) had urine AFP/Cr MoM levels less than 0.31 MoM and 0.5 MoM respectively. CONCLUSION: The establishment of a reference range which allows for gestational differences in AFP/Cr levels is essential for further antenatal testing.
Asunto(s)
Síndrome de Down/diagnóstico , alfa-Fetoproteínas/orina , Adulto , Creatinina/orina , Femenino , Edad Gestacional , Humanos , Embarazo , Valores de ReferenciaRESUMEN
We developed a latex agglutination nephelometric immunoassay for urinary basic fetoprotein (BFP) that functioned well and had good specificity, precision, and recovery. Reference intervals started below 0.5 microgram/L, the lower limit of the range of sensitivity of the assay, and went up to 7.0 micrograms/L at the 97.5th percentile without age- or sex-related variation, in accordance with the NCCLS guidelines. BFP was unstable at pH 5.0 at 4 degrees C and 25 degrees C. The western blot method showed BFP found in the semen to be structurally identical to purified BFP from hepatoma ascites, in which concentration ranged from 94.2 to 145.2 micrograms/L and, further, to have the same molecular weight and reactivity with a monoclonal antibody. BFP levels were elevated in cases urinary BFP concentration included ureter stone, infection, and prostate and bladder cancer. Moreover, BFP concentration correlated closely with that of alpha 2-macroglobulin, indicating that BFP is probably secreted locally in close pathophysiologic association with post-renal hemorrhage. We thus conclude that BFP is a urinary nonspecific marker for inflammation or tumor. The best indication for BFP as a tumor marker may be follow-up when diagnosis of genitourinary cancer is definite.
Asunto(s)
Enfermedades Urogenitales Femeninas/orina , Enfermedades Renales/orina , Enfermedades Urogenitales Masculinas , alfa-Fetoproteínas/orina , Adulto , Anciano , Biomarcadores , Western Blotting , Femenino , Humanos , Concentración de Iones de Hidrógeno , Masculino , Persona de Mediana Edad , Nefelometría y Turbidimetría , Semen/metabolismo , Sensibilidad y EspecificidadRESUMEN
A group of 215 healthy workers of the Bydgoszcz Industrial Works "Pasamon", aged 19-61 years, was examined. Normal values of CEA and AFP in urine were determined using the RIA method. They were 0-42 ng/ml and 0-9 UI/ml, respectively. The increase of CEA was often observed in patients with the urinary tract infections. The cytological examination of urine sediment and determination of CEA level may, in some cases, indicate the difference between the urinary tract infections and urothelial carcinomas.
Asunto(s)
Antígeno Carcinoembrionario/orina , Enfermedades Profesionales/orina , Infecciones Urinarias/orina , Neoplasias Urológicas/orina , alfa-Fetoproteínas/orina , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Exposición Profesional , Valores de ReferenciaRESUMEN
The influence of exposure to tobacco smoke on maternal serum alpha-fetoprotein (AFP) levels at 16 wk gestation was examined. Urinary cotinine levels were used to quantify exposure to tobacco smoke. Significantly higher levels of maternal serum AFP were found in 101 women who had more than 1.0 microgram cotinine/mg urinary creatinine compared with 180 women whose urinary cotinine levels were below this level [(mean +/- SD) 1.23 +/- 0.64 and 1.06 +/- 0.54 respectively; 95 per cent CI of difference of means 0.01-0.31; P < 0.05]. There was a mild albeit statistically significant correlation between urinary cotinine levels and maternal serum AFB (r 0.099; P < 0.05). However, the difference in maternal serum AFP levels between the two groups was not found to be significant, when adjustments for maternal body mass index were made.
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Fumar/efectos adversos , alfa-Fetoproteínas/análisis , Índice de Masa Corporal , Cotinina/orina , Creatinina/orina , Femenino , Humanos , Embarazo , Segundo Trimestre del Embarazo , Radioinmunoensayo , alfa-Fetoproteínas/orinaAsunto(s)
Coproporfirinas/orina , Embolización Terapéutica , Neoplasias Hepáticas Experimentales/orina , Neoplasias Hepáticas/orina , Adulto , Anciano , Alanina Transaminasa/sangre , Animales , Femenino , Humanos , Isomerismo , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas Experimentales/terapia , Masculino , Persona de Mediana Edad , alfa-Fetoproteínas/orinaRESUMEN
We found that urinary fibronectin (UFN) in cancer patients was almost all fragmented and consisted mainly of the cell-binding domain. We developed a two-site immunoenzymometric assay for UFN, using two monoclonal antibodies that both recognize this domain of fibronectin. The amount of UFN was expressed as arbitrary units per milligram of creatinine. Some 2% of the 623 healthy subjects had UFN above the clinical cutoff point (200 arb. units/mg creatinine), as did 14% of the 271 patients with nonmalignant diseases. In contrast, concentrations of UFN exceeded the cutoff point in 59% of the 589 patients with cancer. In 37 patients with gastrointestinal cancer tested for UFN and for one or more of three established serum tumor markers, UFN was found in 25, significantly more often than the other markers. These results indicated that UFN is a marker that may be helpful in evaluating many kinds of cancer.