Areas covered: In this perspective, literature- and empirical evidence is combined with author’s opinions to discuss the progress of ultrahigh resolution MS and provide insight in its potential for validation and development of clinical tests.
Expert commentary: Thus far two ‘low resolution’ MS strategies have been implemented in the clinic: quantification of proteins using triple quadrupole instruments and identification of unknown microorganisms using comparative analysis with spectral libraries on MALDI-TOF instruments. The rise of HRAM technology further boosts the potential of MS-based tests for detection and quantitation of disease-specific biomarkers which meet the analytical performance specifications needed for clinical assays. 相似文献
Areas covered: High-resolution mass spectrometry, coupled with state of the art fractionation systems are revealing the plethora of diagnostic/prognostic proteomic information existing within urinary exosomes, glycoproteins, and proteins. Affinity capture pre-processing techniques such as combinatorial peptide ligand libraries and biomarker harvesting hydrogel nanoparticles are enabling measurement/identification of previously undetectable urinary proteins.
Expert commentary: Future challenges in the urinary proteomics field include a) defining either single or multiple, universally applicable data normalization methods for comparing results within and between individual patients/data sets, and b) defining expected urinary protein levels in healthy individuals. 相似文献
Objective: The aim of this paper is the discovery of new non-invasive biomarker for the monitoring of VHLD patients.
Materials and methods: We compared the urinary proteome of VHLD patients, ccRCC patients and healthy volunteers.
Results: Among all differentially expressed proteins, alpha-1-antitrypsin (A1AT) and APOH (beta-2-glycoprotein-1) are strongly over-abundant only in the urine of VHLD patients with a history of ccRCC.
Discussion and conclusion: A1AT and APOH could be promising non-invasive biomarkers. 相似文献
Areas covered: Beyond microbe identification, MALDI-TOF MS offers great opportunities for fast strain typing and detection of antimicrobial susceptibility/resistance in both bacterial and fungal organisms. Drawing on evidence from PubMed literature searches, clinical microbiology laboratory experience, and the authors’ opinions, this review summarizes recent significant advances and ongoing challenges in these areas.
Expert commentary: In the near future, it is expected that the implementation of new analytical algorithms, automation of procedures, and refinement of assays will enhance the clinical and epidemiological usefulness of MALDI-TOF and other MS technologies. 相似文献
Areas covered: In this review, several proteomic approaches are described in order to help and provide the basis for the identification of biomarkers useful in early diagnosis, also in discovery novel targets for therapeutic agents. In fact, the identification of biomarkers will have a high potential to detect leptomeningeal lymphoma, as well as to predict its progression and treatment response.
Expert commentary: In the case of LM by Central nervous system (CNS) lymphoma, these studies generated the first insights into the utility of proteomic analysis for biomarker identification and will be demonstrated that identifying specific proteins in cerebrospinal fluid (CSF) had much greater sensitivity for detecting LM in comparison to standard cytological protocols. 相似文献
Areas covered: Proteomics is a powerful tool that enables the identification and quantification of novel candidate biomarkers of disease. In this review, we discuss the role of proteomic technologies in biomarker discovery and validation, peripheral blood as a source of protein biomarkers, statistical methods for analyzing proteomic data, and some existing challenges in the field. We also review a selection of previously published studies focused on identifying blood-based diagnostic protein biomarkers of MDD and BD within a ten-year period.
Expert commentary: Proteomic studies have led to the identification of numerous potential biomarkers of MDD and BD. However, clinical validation and translation into clinical practice have not yet been achieved. Conducting large-scale validation studies and addressing various factors that limit the reproducibility of the proteomic findings are key to ensure that robust and reliable biomarker tests are developed and clinically validated. 相似文献
Areas covered: In the present review, we summarize studies using mass spectrometric (MS) approaches to identify protein alterations in the cerebrospinal fluid (CSF) of ALS patients. In total, we identified 11 studies fulfilling our criteria by searching in the PubMed database using the keywords ‘ALS’ and ‘CSF’ combined with ‘proteome’, ‘proteomic’, ‘mass spectrometry’ or ‘protein biomarker’. Ten proteins were differently regulated in ALS CSF compared to controls in at least 2 studies. We will discuss the relevance of the identified proteins regarding the frequency of identification, extent of alteration and brain-specificity.
Expert commentary: Most of the identified CSF biomarker candidates are irreproducible or mainly blood-derived. We assign the missing success of CSF proteomic studies in biomarker discovery to a lack of sensitivity, unsuitable normalization, low quality assurance and variations originating from sample preparation. These issues must be improved in future proteomic studies in CSF. 相似文献
Areas covered: This review is comprised of evidence obtained from literature searches from PubMed. It covers the evidence of diagnostic, prognostic, and predictive biomarkers for gastric cancer using proteomic technologies, and provides up-to-date references.
Expert commentary: The proteomic technologies have not only enabled the screening of a large number of samples, but also enabled the identification of diagnostic, prognostic and predictive biomarkers for gastric cancer. While major challenges still remain, to date, proteomic studies in gastric cancer have provided a wealth of information in revealing proteome alterations associated with the disease. 相似文献
Objective: The study examined the early release kinetics of TnTuORF.
Materials and methods: We analyzed the time course of the release of cardiac troponins I and T and TnTuORF in patients (n?=?31) with hypertrophic obstructive cardiomyopathy undergoing transcoronary ablation of septal hypertrophy (TASH).
Results: Fifteen minutes after TASH, the levels of both troponins increased significantly (cTnT median: 18?ng/L versus 27?ng/L; cTnI median: 15?ng/L versus 25?ng/L). TnTuORF showed no variation.
Discussion: We observed a significantly greater increase in cTnI compared with cTnT.
Conclusion: Our results demonstrate that troponin assays allow early detection of myocardial injury, whereas TnTuORF levels remain unchanged in this setting. 相似文献
Areas covered: The review examines proteomic and genomic techniques for cancer biomarker detection and outlines advantages and challenges of integrating multiple omics approaches to achieve optimal sensitivity and address tumor heterogeneity. This discussion is based on a systematic literature review and direct participation in translational studies.
Expert commentary: Identifying aggressive cancers early on requires improved sensitivity and implementation of biomarkers representative of tumor heterogeneity. During the last decade of genomic and proteomic research, significant advancements have been made in next generation sequencing and mass spectrometry techniques. This in turn has led to a dramatic increase in identification of potential genomic and proteomic cancer biomarkers. However, limited successes have been shown with translation of these discoveries into clinical practice. We believe that the integration of these omics approaches is the most promising molecular tool for comprehensive cancer evaluation, early detection and transition to Precision Medicine in oncology. 相似文献
Objective: The aim of the current study was to evaluate the relation between the change in CRP velocity (CRPv) and 30-d mortality among STEMI patients.
Material and methods: We included consecutive patients with a diagnosis of STEMI who presented to Tel-Aviv Medical Center between 2008 and 2014 and had their CRP measured with a wide range assay (wr-CRP) at least twice during the 24?h after admission. CRPv was defined as the change in wr-CRP concentration (mg/l) divided by the change in time (in hours) between the two measurements.
Results: The study population comprised of 492 patients, mean age was 62?±?14, 80% were male. CRPv was significantly higher among patients who died within 30 d of admission (1.42?mg/l versus 0.18?mg/l, p?<?0.001). In a multivariate regression model adjusted to multiple confounders, CRPv was independently associated with 30-d mortality (OR 1.39, 95% CI: 1.20–1.62, p?<?0.001).
Conclusion: CRPv might be an independent and rapidly measurable biomarker for short-term mortality in patients presenting with STEMI. 相似文献
Areas covered: Herein, we review recent advances in quantitative proteomic technology and their applications in studies to identify intrinsic tumor subtypes of various tumors, to illuminate mechanistic aspects of pharmacological and oncogenic adaptations, and to highlight interaction targets for anti-cancer compounds and cancer-addicted proteins.
Expert commentary: Quantitative proteomic technologies are being successfully employed to classify tumor samples into distinct intrinsic subtypes, to improve existing DNA/RNA based classification methods, and to evaluate the activation status of key signaling pathways. 相似文献
Objective: To evaluate circulatory apoptotic markers and oxidative stress in patients with PCOS.
Materials and methods: Forty-four women with PCOS, and 44 healthy women as controls were enrolled in the study. Oxidative stress parameters and caspases levels were measured in serum.
Results: The caspase 9 level was significantly lower and related with oxidant status in patients with PCOS, while the circulating levels of caspases 3 and 7 were statistically similar in both groups.
Discussion: This study is the first report demonstrating the circulating levels of apoptotic markers and their relationship with oxidant status in PCOS.
Conclusion: The circulating caspase 9 and oxidant status might contribute to apoptotic dysregulation in PCOS. 相似文献
Objective: To establish a panel of protein biomarkers incorporated in a multiplexed microarray (BCa chip) and a classifier for diagnosing recurrent NMIBC.
Materials and methods: Urine samples from 45 patients were tested. Diagnostic performance was evaluated by receiver operating characteristic (ROC) analysis.
Results: A multi biomarker panel (ECadh, IL8, MMP9, EN2, VEGF, past recurrences, BCG therapies and stage at diagnosis) was identified yielding an area under the curve of 0.96.
Discussion and conclusion: This biomarker panel represents a potential diagnostic tool for noninvasive diagnosis of recurrent NMIBC. 相似文献
Areas covered: This review provides an overview of the technological basis, applications and limitations of some of the most commonly used full-length, recombinant protein and protein fragment microarray platforms, including ProtoArray Human Protein Microarrays, HuProt Human Proteome Microarrays, Human Protein Atlas Protein Fragment Arrays, Nucleic Acid Programmable Arrays and Immunome Protein Arrays.
Expert commentary: The choice of appropriate protein microarray platform depends on the specific biological application in hand, with both more focused, lower density and higher density arrays having distinct advantages. Full-length protein arrays offer advantages in biomarker discovery profiling applications, although care is required in ensuring that the protein production and array fabrication methodology is compatible with the required downstream functionality. 相似文献
Methods: We conducted a cross-sectional study of 225 participants (104 men). The levels of hs CRP and fasting lipid parameters were analyzed by COBAS. Body composition was determined with dual-energy X-ray absorptiometry.
Results: Twenty-one (9?%) participants had elevated hs CRP levels (>3?mg/mL). The levels of hs CRP had significant correlations (p?<0.05) with obesity and metabolic variables among women. Stepwise multivariate regression analysis identified FM (%) (accounted for 22.5% of the variability in hs CRP levels) as a major determinant of hs CRP levels. On multivariate regression, FM (%) was the independent determinant of intermediate and elevated hs CRP in women after adjustment for the potential confounders.
Conclusions: Obesity may play a direct role in the elevated hs CRP levels in women, but not men living in Singapore. This is probably due to different body composition or different effects of sex hormones on adipose tissue between men and women. 相似文献
Objective: To explore protein markers of stress in saliva of eight medical residents who performed emergency medicine simulations.
Materials and methods: Saliva was collected before the simulations, after the simulations, and following morning upon waking. Proteins were separated by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), identified by mass spectrometry (MS), and relatively quantified by densitometry.
Results: Salivary alpha-amylase and S–type cystatins significantly increased, while the ~26?kDa and low-molecular weight (MW) (<10?kDa) SDS-PAGE bands exhibited changes after stress.
Discussion and conclusion: Alpha-amylase and cystatins are potential salivary markers of acute stress, but further validation should be performed using larger sample populations. 相似文献
Objective: The objective of this study is to explored novel biomarkers for phospholipidosis using a metabolomic approach.
Method: NMR spectrometry and LC/MS/MS analyses were applied to urine and plasma of rats administrated cationic amphiphilic drugs.
Results: The phenylacetylglycine to hippuric acid ratio in plasma was increased in time and dose-dependent manners; and it was well correlated with histopathological observation.
Conclusion: The plasma phenylacetylglycine to hippuric acid ratio is a potential marker in monitoring drug-induced phospholipidosis. 相似文献
Objective: To study neopterin, protein carbonyl and malondialdehyde (MDA) in EPTB.
Methods: Sixty nine clinically confirmed cases with an equal number of age and sex matched healthy controls were enrolled. Ziehl–Neelsen staining for acid fast bacilli and culture on Lowenstein–Jensen medium were performed on all the extrapulmonary specimens. Serum neopterin and protein carbonyl levels were estimated using commercial ELISA kits. Malondialdehyde was determined by measuring thiobarbituric acid reactive substances.
Results: Serum neopterin, protein carbonyl and MDA levels were significantly discriminative for cases of EPTB from healthy controls (p?<?0.05). Levels of all the three biomarkers under study significantly differed between culture as well as smear positive and negative cases. A positive correlation between neopterin and protein carbonyl was seen among the cases.
Conclusions: So far few studies have integrated combination of validated host biomarkers for active disease in EPTB. Our study suggests the potential diagnostic role of neopterin, protein carbonyl and MDA in EPTB. 相似文献
Objective: To evaluate the circulating proteins as liver biomarkers for the identification of HCC associated with HCV infection in Egyptian patients using LC-MS/MS analysis.
Methods: Blood sera were collected from 31 HCC patients and the fractionated proteins were subjected to LC-MS/MS analysis. Protein candidates were validated by enzyme-linked immunosorbent assay (ELISA).
Results: Thirty-three proteins were significantly identified in the sera of HCC patients with persistent HCV infection. These proteins are involved in several biological processes including acute phase response, complement activation, hemostasis process and lipid metabolism. The level of lectin galactoside-binding soluble 3 binding protein (LGALS3BP), Kininogen-1 (KNG1), serum amyloid A2 (SAA2) and paraoxonase 1 (PON1) and alpha-fetoprtoein (AFP) were elevated in serum.
Conclusion: In HCC patients with chronic HCV infection, we identified a group of differentially expressed circulating proteins involved in regulating different cellular mechanisms. 相似文献