Abstract:
BACKGROUND:Current noninvasive assays for urothelial carcinoma (UC) lack clinical sensitivity and specificity. Given the utility of plasma cell-free DNA (cfDNA) biomarkers, the development of urinary cfDNA biomarkers may improve the diagnostic sensitivity. METHODS:We assessed copy number alterations (CNAs) by shallow genome-wide sequencing of urinary cfDNA in 95 cancer-free individuals and 65 patients with UC, 58 with kidney cancer, and 45 with prostate cancer. We used a support vector machine to develop a diagnostic classifier based on CNA profiles to detect UC (UCdetector). The model was further validated in an independent cohort (52 patients). Genome sequencing data of tumor specimens from 90 upper tract urothelial cancers (UTUCs) and CNA data for 410 urothelial carcinomas of bladder (UCBs) from The Cancer Genome Atlas were used to validate the classifier. Genome sequencing data for urine sediment from 32 patients with UC were compared with cfDNA. To monitor the treatment efficacy, we collected cfDNA from 7 posttreatment patients. RESULTS:Urinary cfDNA was a more sensitive alternative to urinary sediment. The UCdetector could detect UC at a median clinical sensitivity of 86.5% and specificity of 94.7%. UCdetector performed well in an independent validation data set. Notably, the CNA features selected by UCdetector were specific markers for both UTUC and UCB. Moreover, CNA changes in cfDNA were consistent with the treatment effects. Meanwhile, the same strategy could localize genitourinary cancers to tissue of origin in 70.1% of patients. CONCLUSIONS:Our findings underscore the potential utility of urinary cfDNA CNA profiles as a basis for noninvasive UC detection and surveillance.
journal_name
Clin Chemjournal_title
Clinical chemistryauthors
Ge G,Peng D,Guan B,Zhou Y,Gong Y,Shi Y,Hao X,Xu Z,Qi J,Lu H,Zhang X,Zhan Y,Li Y,Wu Y,Ding G,Shen Q,He Q,Li X,Zhou L,Ci Wdoi
10.1373/clinchem.2019.309633subject
Has Abstractpub_date
2020-01-01 00:00:00pages
188-198issue
1eissn
0009-9147issn
1530-8561pii
clinchem.2019.309633journal_volume
66pub_type
杂志文章abstract:BACKGROUND:Serial measurements of neurohormones have been shown to improve prognostication in the setting of acute heart failure (HF) or chronic HF without therapeutic intervention. We investigated the prognostic role of serial measurements of emerging neurohormones and BNP in a cohort of chronic HF patients undergoing...
journal_title:Clinical chemistry
pub_type: 杂志文章
doi:10.1373/clinchem.2009.125856
更新日期:2010-01-01 00:00:00
abstract::We describe optimal conditions for immobilization of two monoclonal antibodies to progesterone for solid-phase assays. Polystyrene surfaces are refined with Protein A to achieve uniform, reproducible, stable, and sterically accessible immobilization of immunoglobulins (IgG). To this end, we optimized the amount of imm...
journal_title:Clinical chemistry
pub_type: 杂志文章
doi:
更新日期:1987-08-01 00:00:00
abstract:BACKGROUND:Studies of the effects of tobacco smoke often rely on reported exposure to cigarette smoke, a measure that is subject to bias. We describe here the relationship between parental smoking exposure as assessed by urinary cotinine excretion and lung function in children with asthma. METHODS:We studied 90 childr...
journal_title:Clinical chemistry
pub_type: 临床试验,杂志文章
doi:
更新日期:1999-04-01 00:00:00
abstract:BACKGROUND:Because reference values for vitamin B(12) concentrations and vitamin B(12)-binding capacities for pregnant women have not been established, the reference values for nonpregnant women are often applied to assess vitamin B(12) status. The aim of the present study was to describe ranges of biochemical indices ...
journal_title:Clinical chemistry
pub_type: 杂志文章
doi:
更新日期:2002-06-01 00:00:00
abstract::We evaluated a new discrete analyzer, the Hitachi 705. The instrument can process sequentially as many as 19 different enzymes or other analytes, with a throughput of 180 tests per hour. We evaluated the spectrophotometer, the sample and reagent probes, and the performance for 11 assays: creatine kinase, aspartate ami...
journal_title:Clinical chemistry
pub_type: 杂志文章
doi:
更新日期:1983-04-01 00:00:00
abstract::We report another patient with a circulating alkaline phosphatase/immunoglobulin complex in his blood, and describe a simple method of demonstrating such complexes. On electrophoresis on cellulose acetate, the complex was relatively slow moving and there was no activity in the normal bone/liver isoenzyme region. When ...
journal_title:Clinical chemistry
pub_type: 杂志文章
doi:
更新日期:1980-10-01 00:00:00
abstract::A patient with the hyperviscosity syndrome exhibited very high concentrations of intermediate to small circulating immune complexes (CIC), involving 40-50% of the IgG present, with IgG rheumatoid factor activity. We demonstrate that precipitation of CIC by polyethylene glycol in the reaction mixture caused interferenc...
journal_title:Clinical chemistry
pub_type: 杂志文章
doi:
更新日期:1988-04-01 00:00:00
abstract::The values of apolipoproteins (apo) A-I and B were determined in a population sample of hospital outpatients with a standardized method to verify if the cutpoints calculated in a cross-sectional study in the US are usable with other populations. We also tested the apolipoproteins' ability to discriminate between healt...
journal_title:Clinical chemistry
pub_type: 杂志文章
doi:
更新日期:1998-01-01 00:00:00
abstract::The isoenzyme pattern of N-acetyl-beta-glucosaminidase (NAG) in serum and urine was studied in two groups of patients with diabetes mellitus and in 30 control subjects. Total NAG activity was significantly (P less than 0.001) increased in the serum and urine of the 20 diabetics with vascular complications, but was ins...
journal_title:Clinical chemistry
pub_type: 杂志文章
doi:
更新日期:1988-12-01 00:00:00
abstract::Biological variation is inherent in all medical tests and is a major source of error in clinical test interpretation. We use inherent test error due to biological variability as the touchstone by which to validate the clinical acceptability of analytical goals. Analytical goals should consist of sets of complementary ...
journal_title:Clinical chemistry
pub_type: 杂志文章,评审
doi:
更新日期:1993-07-01 00:00:00
abstract::The serum pancreolauryl test has limited sensitivity for detecting mild pancreatic insufficiency. The aim of this study was to optimize the serum pancreolauryl test so as to increase the probability of positive results in patients with chronic pancreatitis. The study had three parts. First, the sampling time was optim...
journal_title:Clinical chemistry
pub_type: 临床试验,杂志文章
doi:
更新日期:1998-04-01 00:00:00
abstract:BACKGROUND:Meconium analysis is a diagnostically sensitive and objective alternative to maternal self-report for detecting prenatal tobacco exposure. Nicotine and metabolite disposition in meconium is poorly characterized, and correlation of analytes' concentrations with neonatal outcomes is unexplored. Our objectives ...
journal_title:Clinical chemistry
pub_type: 杂志文章
doi:10.1373/clinchem.2008.109173
更新日期:2008-12-01 00:00:00
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journal_title:Clinical chemistry
pub_type: 杂志文章
doi:
更新日期:1975-05-01 00:00:00
abstract::Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is a recessively inherited defect in the mitochondrial beta-oxidation of fatty acids. A single nucleotide change, the A985 --> G transition, in the MCAD gene accounts for approximately 90% of all the disease-causing mutations in the patients. We have used PCR to am...
journal_title:Clinical chemistry
pub_type: 杂志文章
doi:
更新日期:1998-01-01 00:00:00
abstract:BACKGROUND:Laboratory tests can be an important source of blood loss in hospitals, especially for newborns and patients in intensive care. The aim of this study was to quantify blood loss for laboratory diagnostic tests in a large number of patients in a teaching hospital. METHODS:We estimated blood loss by multiplyin...
journal_title:Clinical chemistry
pub_type: 杂志文章
doi:10.1373/49.10.1651
更新日期:2003-10-01 00:00:00
abstract::We describe a sensitive beta-endorphin (beta-EP) radioimmunoassay specific for beta-EP 1-31 applied to human ventricular and lumbar cerebrospinal fluid (CSF). Specificity was documented by reversed-phase HPLC of CSF pools. Simultaneous ventricular and lumbar CSF samples from 13 patients suspected of having normal-pres...
journal_title:Clinical chemistry
pub_type: 杂志文章
doi:
更新日期:1992-06-01 00:00:00
abstract::We studied the relationship between serum erythropoietin (EPO) concentration and iron status in 67 patients undergoing chronic hemodialysis. Serum concentrations of EPO were measured by RIA with recombinant human EPO. The geometric mean of the serum EPO concentration was 10.9 int. units/L (mean +/- SD range = 7.8 - 15...
journal_title:Clinical chemistry
pub_type: 杂志文章
doi:
更新日期:1992-02-01 00:00:00
abstract::We examined the mechanism by which hypertriglyceridemia interferes with the Roche Diagnostics "Amylochrome" procedure for measurement of amylase in lactescent samples with normal and above-normal amylase activity. The serum blank recommended in the Amylochrome protocol to compensate for lactescence remains inappropria...
journal_title:Clinical chemistry
pub_type: 杂志文章
doi:
更新日期:1982-10-01 00:00:00
abstract:BACKGROUND:Recurrent pregnancy loss, (RPL) affecting 1%-2% of couples, is defined as ≥3 consecutive pregnancy losses before 20-week' gestation. Women with RPL are routinely screened for etiological factors, but routine screening of male partners is not currently recommended. Recently it has been suggested that sperm qu...
journal_title:Clinical chemistry
pub_type: 杂志文章
doi:10.1373/clinchem.2018.289348
更新日期:2019-01-01 00:00:00
abstract::We review atomic flame spectrometry of metals based on the selective laser-enhancement of the rate of atomic ionization. A discussion of basic principles, prior literature, and instrumentation is followed by an overview of analytical figures of merit for the technique, and a look at its present status and areas for fu...
journal_title:Clinical chemistry
pub_type: 杂志文章
doi:
更新日期:1983-09-01 00:00:00
abstract::This case demonstrates the importance of monitoring theophylline concentrations in serum during therapy with this drug. The commonly used body-weight-derived guidelines for therapeutic dose are not adequate and do not preclude the necessity for such monitoring. The ultraviolet spectrophotometric methods available for ...
journal_title:Clinical chemistry
pub_type: 杂志文章
doi:
更新日期:1978-09-01 00:00:00
abstract:BACKGROUND:Few data compare cardiac troponin T (cTnT) and cardiac troponin I (cTnI) in a general population. We sought to evaluate the distribution and association between cTnT, cTnI, and cardiovascular risk factors in a large general population cohort. METHODS:High-sensitivity cTnT and cTnI were measured in serum fro...
journal_title:Clinical chemistry
pub_type: 杂志文章
doi:10.1373/clinchem.2018.292086
更新日期:2018-11-01 00:00:00
abstract:BACKGROUND:Vascular age is an emerging health indicator and predictor of end-organ damage to the heart, brain, and kidney. Although there have been many review publications concerning risk factors for vascular aging, most include cross-sectional epidemiological studies, limiting inferences about temporality. There is a...
journal_title:Clinical chemistry
pub_type: 杂志文章,评审
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更新日期:2019-01-01 00:00:00
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journal_title:Clinical chemistry
pub_type: 杂志文章
doi:
更新日期:1999-09-01 00:00:00
abstract::We describe a simple and convenient method for processing small amounts of tissue samples for trace-metal measurements by atomic absorption spectrometry, by use of a modified Parr microwave digestion bomb. Digestion proceeds rapidly (less than or equal to 90 s) in a sealed Teflon-lined vessel that eliminates contamina...
journal_title:Clinical chemistry
pub_type: 杂志文章
doi:
更新日期:1989-03-01 00:00:00
abstract::This time-resolved immunofluorometric assay (IFMA) developed for measurement of placental protein 5 (PP5) involves two antibodies: a monoclonal anti-PP5 antibody attached to a solid phase and an europium(III) chelate-labeled polyclonal anti-PP5 antibody as a tracer. The measuring range is 0.05-100 micrograms/L and the...
journal_title:Clinical chemistry
pub_type: 杂志文章
doi:
更新日期:1988-08-01 00:00:00
abstract::Four assay procedures for tobramycin in serum--enzyme immunoassay (I), substrate-labeled fluorescent immunoassay (II), radioimmunoassay (III), and bioassay (IV)--were compared and evaluated by replicate and analytical recovery studies. I and II were about 50% more precise than III and IV. II was substantially more nea...
journal_title:Clinical chemistry
pub_type: 杂志文章
doi:
更新日期:1982-01-01 00:00:00
abstract:BACKGROUND:PS-341, a selective inhibitor of the proteasome, currently is under evaluation as an anticancer agent in multiple phase I clinical trials. In animal-model studies, PS-341 was rapidly removed from the vascular compartment and distributed widely, quickly approaching the limits of detection. An accurate pharmac...
journal_title:Clinical chemistry
pub_type: 杂志文章
doi:
更新日期:2000-05-01 00:00:00
abstract::We have evaluated a new immunoenzymatic assay for human thyrotropin involving three monoclonal antibodies (Abbott HTSH EIA) and compared the results with those of two conventional nonequilibrium double-antibody radioimmunoassay (RIA) methods: Clinical Assays' RIA and a research RIA (J Clin Endocrinol Metab 1975; 41:67...
journal_title:Clinical chemistry
pub_type: 杂志文章
doi:
更新日期:1986-03-01 00:00:00
abstract::Using the Selected Method of McKenzie and Henderson (Selected Methods Clin Chem 1983;10:59-67) as a reference method, we compared the performance of 10 commercially available methods for determination of lactate dehydrogenase (LD, EC 1.1.1.27) isoenzymes. Results were expressed as percentage of total LD activity, as d...
journal_title:Clinical chemistry
pub_type: 杂志文章
doi:
更新日期:1988-09-01 00:00:00