Abstract:
BACKGROUND:Extracellular vesicles (EVs) contain a rich cargo of different RNA species with specialized functions and clinical applications. However, the landscape and characteristics of extracellular vesicle long RNA (exLR) in human blood remain largely unknown. METHODS:We presented an optimized strategy for exLR sequencing (exLR-seq) of human plasma. The sample cohort included 159 healthy individuals, 150 patients with cancer (5 cancer types), and 43 patients with other diseases. Bioinformatics approaches were used to analyze the distribution and features of exLRs. Support vector machine algorithm was performed to construct the diagnosis classifier, and diagnostic efficiency was evaluated by ROC analysis. RESULTS:More than 10000 exLRs, including mRNA, circRNA, and lncRNA, were reliably detected in each exLR-seq sample from 1-2 mL of plasma. We observed that blood EVs contain a substantial fraction of intact mRNAs and a large number of assembling spliced junctions; circRNA was also enriched in blood EVs. Interestingly, blood exLRs reflected their tissue origins and the relative fractions of different immune cell types. Additionally, the exLR profile could distinguish patients with cancer from healthy individuals. We further showed that 8 exLRs can serve as biomarkers for hepatocellular carcinoma (HCC) diagnosis with high diagnostic efficiency in training [area under the curve (AUC) = 0.9527; 95% CI, 0.9170-0.9883], validation cohort (AUC = 0.9825; 95% CI, 0.9606-1), and testing cohort (AUC = 0.9627; 95% CI, 0.9263-0.9991). CONCLUSIONS:In summary, this study revealed abundant exLRs in human plasma and identified diverse specific markers potentially useful for cancer diagnosis.
journal_name
Clin Chemjournal_title
Clinical chemistryauthors
Li Y,Zhao J,Yu S,Wang Z,He X,Su Y,Guo T,Sheng H,Chen J,Zheng Q,Li Y,Guo W,Cai X,Shi G,Wu J,Wang L,Wang P,He X,Huang Sdoi
10.1373/clinchem.2018.301291subject
Has Abstractpub_date
2019-06-01 00:00:00pages
798-808issue
6eissn
0009-9147issn
1530-8561pii
clinchem.2018.301291journal_volume
65pub_type
杂志文章abstract:BACKGROUND:The emergence of a novel pandemic human strain of influenza A (H1N1/09) has clearly demonstrated the need for flexible tools enabling the rapid development of new diagnostic methods. METHODS:We designed a set of reverse-transcription quantitative real-time PCR (RT-qPCR) assays based on the Universal ProbeLi...
journal_title:Clinical chemistry
pub_type: 杂志文章
doi:10.1373/clinchem.2009.136192
更新日期:2009-12-01 00:00:00
abstract:BACKGROUND:Measurement of postimmunization antibody response to pneumococcal capsular polysaccharide (caps-PS) is the standard method to identify deficiency of antipolysaccharide antibody production. However, no standardized criteria have been defined for classification of patients into responders or nonresponders to c...
journal_title:Clinical chemistry
pub_type: 杂志文章
doi:10.1373/clinchem.2006.080051
更新日期:2007-03-01 00:00:00
abstract:BACKGROUND:PCR-based mutation detection is prone to methodological errors, e.g., in restriction length fragment polymorphism (RFLP) and allele-specific amplification (ASA), false PCR results may occur because of technical faults or atypical new mutations. METHODS:We investigated the ability of a genotyping assay based...
journal_title:Clinical chemistry
pub_type: 杂志文章
doi:
更新日期:1999-12-01 00:00:00
abstract::The new oral formulation of cyclosporine (CsA), Neoral (CsA-N), results in increased area under the curve (AUC) and decreased intra- and interindividual variation in blood concentrations and other pharmacokinetic (PK) parameters when compared with the current Sand-immune (CsA-S) formulation. The present study examines...
journal_title:Clinical chemistry
pub_type: 杂志文章
doi:
更新日期:1997-01-01 00:00:00
abstract:BACKGROUND:In malignancy, gene mutations frequently occur in tumor suppressor genes such as p53 and are sporadically located. We describe a homogeneous method for amplification and mutation scanning, and apply the method to the p53 gene. METHODS:Using a series of overlapping fluorescein-labeled oligonucleotides comple...
journal_title:Clinical chemistry
pub_type: 杂志文章
doi:
更新日期:2002-08-01 00:00:00
abstract:BACKGROUND:Immune repertoire sequencing of the T-cell receptor can identify clonotypes that have expanded as a result of antigen recognition or hematological malignancies. However, current sequencing protocols display limitations with nonuniform amplification and polymerase-induced errors during sequencing. Here, we de...
journal_title:Clinical chemistry
pub_type: 杂志文章
doi:10.1093/clinchem/hvaa159
更新日期:2020-09-01 00:00:00
abstract::Peroxidation of lipids is believed to play a key role in various degenerative diseases. However, few simple tests are able to detect individual susceptibility or resistance to peroxidation. Measurement of the basal concentrations of lipid peroxides in plasma is not satisfactory because they are so low. Therefore, we d...
journal_title:Clinical chemistry
pub_type: 杂志文章
doi:
更新日期:1991-10-01 00:00:00
abstract::The pattern of organic acids in urine from 15 normal newborn infants was investigated by gas chromatography/mass spectrometry of trimethylsilylated derivatives. The urine contains large amounts of succinic, fumaric, 2-ketoglutaric, and 3-hydroxy-3-methylglutaric acids, which are all fairly small components of urine fr...
journal_title:Clinical chemistry
pub_type: 杂志文章
doi:
更新日期:1976-01-01 00:00:00
abstract::We used gas chromatography-mass spectrometry to analyze serum specimens from a patient whose metabolic ketoacidosis resulted from sniffing a toluene-containing substance; we also analyzed a sample of the abused substance itself and a serum specimen from a normal subject. The blood samples from the patient showed abnor...
journal_title:Clinical chemistry
pub_type: 杂志文章
doi:
更新日期:1988-12-01 00:00:00
abstract:BACKGROUND:Mass spectrometric assays could potentially replace protein immunoassays in many applications. Previous studies have demonstrated the utility of liquid chromatography-multiple-reaction monitoring-mass spectrometry (LC-MRM/MS) for the quantification of proteins in biological samples, and many examples of the ...
journal_title:Clinical chemistry
pub_type: 杂志文章
doi:10.1373/clinchem.2011.173856
更新日期:2012-04-01 00:00:00
abstract::Plasma hydroxyproline fractions--free-plus-peptide and free--were determined by a method involving centrifugal ultrafiltration and the procedure of Kivirikko et al. [Anal. Biochem. 19, 249 (1967)]. Within- and between-day precision (CV) for the combined fractions was 4--5% and 2.8--6%, respectively. Mean analytical re...
journal_title:Clinical chemistry
pub_type: 杂志文章
doi:
更新日期:1978-02-01 00:00:00
abstract::Published estimates of the imprecision characteristics of immunoassays are often based on quantities of data that seem to be inadequate. The increasing use of imprecision profiles has not necessarily improved the situation. We describe and illustrate a method of computing 95% confidence intervals for profiles estimate...
journal_title:Clinical chemistry
pub_type: 杂志文章
doi:
更新日期:1990-07-01 00:00:00
abstract::Erythrocyte and plasma cholinesterase activities were measured biweekly in one group of 22 subjects for a year and daily for three weeks in another group of nine men. The average range [i.e., (range/mean) X 100] of activity of erythrocyte cholinesterase in men during a year was 8% and during three weeks was 5%. For pl...
journal_title:Clinical chemistry
pub_type: 杂志文章
doi:
更新日期:1975-12-01 00:00:00
abstract::In the diagnosis of chronic (as opposed to acute) liver diseases, combinations of indicators are needed to improve specificity. Alanine aminopeptidase (AAP; microsomal aminopeptidase, EC 3.4.11.2) activity in serum reportedly is a very sensitive indicator of intrahepatic cholestasis and biliary obstruction; it is also...
journal_title:Clinical chemistry
pub_type: 杂志文章
doi:
更新日期:1987-03-01 00:00:00
abstract:BACKGROUND:The prognostic value of changes in paraprotein markers after stem cell transplantation is unknown. We evaluated disease response using serum immunofixation (s-IFIX), total kappa and lambda ratio (KLR), and free light chain (FLC) ratio in myeloma patients who underwent autologous or autologous plus allogeneic...
journal_title:Clinical chemistry
pub_type: 杂志文章
doi:10.1373/clinchem.2009.124370
更新日期:2009-08-01 00:00:00
abstract:BACKGROUND:Since its beginnings, newborn screening for cystic fibrosis (CF) using an assay for immunoreactive trypsinogen (IRT) has been plagued by a high rate of false-positive results (screen positive, diagnosis negative), despite attempts to reduce this rate by use of altered cutoffs and second-tier DNA testing. IRT...
journal_title:Clinical chemistry
pub_type: 杂志文章
doi:10.1373/clinchem.2009.132480
更新日期:2010-03-01 00:00:00
abstract:BACKGROUND:The thiopurine S:-methyltransferase (TPMT) genetic polymorphism has a significant clinical impact on the toxicity of thiopurine drugs, which are used in the treatment of leukemia and as immunosuppressants. To date, 10 mutant alleles are known that are associated with intermediate or low TPMT activity. To fac...
journal_title:Clinical chemistry
pub_type: 杂志文章
doi:
更新日期:2001-03-01 00:00:00
abstract::We compared the performance of three methods for quantifying high-density lipoprotein cholesterol (HDL-C) with the Reference Method for HDL-C, using samples with a wide range of triglyceride (TG) concentrations (290-18000 mg/L). All three comparison assays-- utilizing a magnetic dextran sulfate precipitating reagent, ...
journal_title:Clinical chemistry
pub_type: 杂志文章
doi:
更新日期:1996-05-01 00:00:00
abstract:BACKGROUND:Astilbin is a flavonoid isolated from the rhizome of Smilax glabra. In a previous study, we revealed its unique immunosuppressive activity, a selective inhibition against activated T lymphocytes. This characteristic of astilbin is beneficial for the treatment of human immune diseases. METHODS:We incubated a...
journal_title:Clinical chemistry
pub_type: 杂志文章
doi:10.1373/clinchem.2006.077297
更新日期:2007-03-01 00:00:00
abstract::In this assay for lactate dehydrogenase (EC 1.1.1.27) isoenzyme 1 (LD-1), 1,6-hexanediol is added to serum after total LD has been measured. After incubation for 5 min the total LD remaining is determined. Samples from patients who had a myocardial infarction or who had undergone bypass surgery were assayed simultaneo...
journal_title:Clinical chemistry
pub_type: 杂志文章
doi:
更新日期:1987-04-01 00:00:00
abstract::For 51 liver allograft recipients, we evaluated whether serum profiles of delta (Bd) and conjugated bilirubins (Bc) could be used to diagnose rejection during the first 30-50 postoperative days, in comparison with histology as the "gold standard." Daily measurements of aspartate aminotransferase, alkaline phosphatase,...
journal_title:Clinical chemistry
pub_type: 杂志文章
doi:
更新日期:1990-01-01 00:00:00
abstract::Determination of the concentration of erythrocyte folate by means of competitive protein binding assay critically depends on the extraction procedure applied. Results will be influenced by variable factors such as the in vitro age of the blood samples, the degree of hemolysis, the presence of ascorbic acid, and the pH...
journal_title:Clinical chemistry
pub_type: 杂志文章
doi:
更新日期:1976-07-01 00:00:00
abstract:BACKGROUND:Disease-defining chromosomal translocations are seen in various neoplasms, especially in lymphomas and leukemias. Translocation detection at the DNA level is often complicated by chromosomal breakpoints that are distributed over very large regions. We have developed a ligation-based assay [the looped ligatio...
journal_title:Clinical chemistry
pub_type: 杂志文章
doi:10.1373/clinchem.2016.270140
更新日期:2017-07-01 00:00:00
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journal_title:Clinical chemistry
pub_type: 杂志文章
doi:
更新日期:1980-06-01 00:00:00
abstract::We present the results of measurements of alkaline phosphatase activity from interlaboratory transferability studies conducted by 12 laboratories in five countries. The variability, as demonstrated by within-day precision (CV less than or equal to 2.6%), between-day precision (CV less than or equal to 3.6%), and betwe...
journal_title:Clinical chemistry
pub_type: 杂志文章
doi:
更新日期:1984-05-01 00:00:00
abstract::The molar absorptivity of unconjugated bilirubin in caffeine reagent is independent of the protein matrix. This finding, together with the simplicity of a dilution step for direct spectrophotometry, will improve the calibration methods of bilirubin and make them more nearly accurate. This is encouraging for the develo...
journal_title:Clinical chemistry
pub_type: 杂志文章
doi:
更新日期:1986-07-01 00:00:00
abstract::Time-resolved fluoroimmunoassay was developed for the detection of synovial-type phospholipase A2 (s-PLA2) in human serum. This solid-phase, sandwich assay uses a polyclonal rabbit antibody raised against synovial-type group II PLA2 produced in Escherichia coli. No cross-reactions were detected between s-PLA2 and PLA2...
journal_title:Clinical chemistry
pub_type: 杂志文章
doi:
更新日期:1992-09-01 00:00:00
abstract::The difference in absorbance (delta A) between equimolar acid and alkaline solutions of methyl red, at a wavelength near the isosbestic point of the indicator, is reproducible. Furthermore, this delta A is sensitive to changes in the wavelength calibration of the instrument used to make the measurement. The delta A of...
journal_title:Clinical chemistry
pub_type: 杂志文章
doi:
更新日期:1986-01-01 00:00:00
abstract::We compared cotinine, carboxyhemoglobin, and thiocyanate concentrations in blood sampled from 187 cigarette smokers and 181 non-smokers. All three differed significantly between smokers and non-smokers. Cotinine performed best as a test for assessing smoking status, with a sensitivity of 98% as compared with 94% for c...
journal_title:Clinical chemistry
pub_type: 杂志文章
doi:
更新日期:1984-08-01 00:00:00
abstract::We measured the cross reactivity of two medications--digitoxin and spironolactone--in two digoxin radioimmunoassay (liquid and solid-phase) kit procedures. Both tests showed similar average percentages of cross reactivity with digitoxin (7.2 and 8.9% for intravenous, and 11.9 and 10.9% for oral administration), but no...
journal_title:Clinical chemistry
pub_type: 杂志文章
doi:
更新日期:1978-04-01 00:00:00