Important options available — from start to finish — for translating proteomics results to clinical chemistry

Heegaard, Niels H. H.; Østergaard, Ole; Bahl, Justyna M.C.; Overgaard, Martin; Beck, Hans Christian; Rasmussen, Lars Melholt; Larsen, Martin R.

doi:10.1002/prca.201400137

Cited by 8 publications

(4 citation statements)

References 127 publications

(157 reference statements)

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“…In recent years, the MRM-MS method has gained immense popularity within the field of proteomics based on its application in biomarker development studies [33,34]. Our study demonstrates how targeted MS applied to a classic nested case-control study, when adequately powered to detect subtle differences in serum protein levels, can support the development of multimarker models with better disease prediction.…”

Section: Discussionmentioning

confidence: 83%

First-trimester multimarker prediction of gestational diabetes mellitus using targeted mass spectrometry

et al. 2016

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Aims/hypothesis Gestational diabetes mellitus (GDM) is associated with an increased risk of pre-eclampsia, macrosomia and the future development of type 2 diabetes mellitus in both mother and child. Although an early and accurate prediction of GDM is needed to allow intervention and improve perinatal outcome, no single protein biomarker has yet proven useful for this purpose. In the present study, we hypothesised that multimarker panels of serum proteins can improve firsttrimester prediction of GDM among obese and non-obese women compared with single markers. Methods A nested case-control study was performed on firsttrimester serum samples from 199 GDM cases and 208 controls, each divided into an obese group (BMI ≥27 kg/m 2 ) and a non-obese group (BMI <27 kg/m 2 ). Based on their biological relevance to GDM or type 2 diabetes mellitus or on their previously reported potential as biomarkers for these diseases, a number of proteins were selected for targeted nano-flow liquid chromatography (LC) MS analysis. This resulted in the development and validation of a 25-plex multiple reaction monitoring (MRM) MS assay. Results After false discovery rate correction, six proteins remained significantly different (p<0.05) between obese GDM patients (n=135) and BMI-matched controls (n=139). These included adiponectin, apolipoprotein M and apolipoprotein D. Multimarker models combining protein levels and clinical data were then constructed and evaluated by receiver operating characteristic (ROC) analysis. For the obese, nonobese and all GDM groups, these models achieved marginally higher AUCs compared with adiponectin alone. Conclusions/interpretation Multimarker models combining protein markers and clinical data have the potential to predict women at a high risk of developing GDM.

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Section: Discussionmentioning

confidence: 83%

First-trimester multimarker prediction of gestational diabetes mellitus using targeted mass spectrometry

et al. 2016

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“…The obstacles that have to be overcome prior to the introduction of new diagnostic procedures have recently been discussed in detail . Specifically, the necessity of rigorous validation of new test utilities—preferentially in interventional trials—is rarely fulfilled . In essence, such investigations have to verify whether the new application is improving the current state‐of‐the‐art diagnosis.…”

Section: Implementation Of New Diagnostic Methodsmentioning

confidence: 99%

Clinical applications of MS‐based protein quantification

Sabbagh

Mindt

Neumaier

et al. 2016

Proteomics Clinical Apps

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Mass spectrometry-based assays are increasingly important in clinical laboratory medicine and nowadays are already commonly used in several areas of routine diagnostics. These include therapeutic drug monitoring, toxicology, endocrinology, pediatrics, and microbiology. Accordingly, some of the most common analyses are therapeutic drug monitoring of immunosuppressants, vitamin D, steroids, newborn screening, and bacterial identification. However, MS-based quantification of peptides and proteins for routine diagnostic use is rather rare up to now despite excellent analytical specificity and good sensitivity. Here, we want to give an overview over current fit-for-purpose assays for MS-based protein quantification. Advantages as well as challenges of this approach will be discussed with focus on feasibility for routine diagnostic use.

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“…The SRM/MRM technique is considered the gold standard proteomic quantification method for predefined sets of proteins [ 50 ]. SRM is a nonscanning method that is performed on triple quadrupole-type instruments (QqQ) [ 51 ]. The first quadrupole (Q1) is used to isolate specified precursor ions, the second quadrupole (Q2) serves as the collision cell to activate and dissociate the precursor ion, and the third quadrupole (Q3) is used to isolate the specific product ion [ 52 ].…”

Section: Proteomics In Prostate Cancer Biomarker Discoverymentioning

confidence: 99%

Approaches to the discovery of non-invasive urinary biomarkers of prostate cancer

2018

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Prostate cancer (PCa) continues to be one of the most common cancers in men worldwide. Prostate specific antigen (PSA) measured in blood has been used for decades as an aid for physicians to detect the presence of prostate cancer. However, the PSA test has limited sensitivity and specificity, leading to unnecessary biopsies, overdiagnosis and overtreatment of patients. For these reasons, there is an urgent need for more accurate PCa biomarkers that can detect PCa with high sensitivity and specificity. Urine is a unique source of potential protein biomarkers that can be measured in a non-invasive way. This review comprehensively summarizes state of the art approaches used in the discovery and validation of urinary biomarkers for PCa. Numerous strategies are currently being used in the discovery of urinary biomarkers for prostate cancer including gel-based separation techniques, mass spectrometry, activity-based proteomic assays and software approaches. Antibody-based approaches remain preferred method for validation of candidate biomarkers with rapidly advancing multiplex immunoassays and MS-based targeted approaches. In the last decade, there has been a dramatic acceleration in the development of new techniques and approaches in the discovery of protein biomarkers for prostate cancer including computational, statistical and data mining methods. Many urinary-based protein biomarkers have been identified and have shown significant promise in initial studies. Examples of these potential biomarkers and the methods utilized in their discovery are also discussed in this review.

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Important options available — from start to finish — for translating proteomics results to clinical chemistry

Cited by 8 publications

References 127 publications

First-trimester multimarker prediction of gestational diabetes mellitus using targeted mass spectrometry

First-trimester multimarker prediction of gestational diabetes mellitus using targeted mass spectrometry

Clinical applications of MS‐based protein quantification

Approaches to the discovery of non-invasive urinary biomarkers of prostate cancer

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