Development of a label‐free LC‐MS/MS strategy to approach the identification of candidate protein biomarkers of disease recurrence in prostate cancer patients in a clinical trial of combined hormone and radiation therapy

Morrissey, Brian M.; O'Shea, Carmel; Armstrong, John G.; Rooney, Cathy; Staunton, Lisa; Sheehan, Martina; Shannon, Aoife M.; Pennington, Stephen R.

doi:10.1002/prca.201300004

Cited by 19 publications

(20 citation statements)

References 42 publications

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“…Indeed the MRM approach has been implemented in several large-scale biomarker studies over the past couple of years. These assays have so far proved particularly useful in the field of toxicology and oncology [ 71 – 73 ]. This technique has not yet been exploited to its full potential in rheumatology, but evidence supporting its potential utility does exist.…”

Section: An Emerging Mass Spectrometry Technologymentioning

confidence: 99%

Early biomarkers of joint damage in rheumatoid and psoriatic arthritis

Ardle¹,

Flatley²,

Pennington³

et al. 2015

Arthritis Res Ther

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Joint destruction, as evidenced by radiographic findings, is a significant problem for patients suffering from rheumatoid arthritis and psoriatic arthritis. Inherently irreversible and frequently progressive, the process of joint damage begins at and even before the clinical onset of disease. However, rheumatoid and psoriatic arthropathies are heterogeneous in nature and not all patients progress to joint damage. It is therefore important to identify patients susceptible to joint destruction in order to initiate more aggressive treatment as soon as possible and thereby potentially prevent irreversible joint damage. At the same time, the high cost and potential side effects associated with aggressive treatment mean it is also important not to over treat patients and especially those who, even if left untreated, would not progress to joint destruction. It is therefore clear that a protein biomarker signature that could predict joint damage at an early stage would support more informed clinical decisions on the most appropriate treatment regimens for individual patients. Although many candidate biomarkers for rheumatoid and psoriatic arthritis have been reported in the literature, relatively few have reached clinical use and as a consequence the number of prognostic biomarkers used in rheumatology has remained relatively static for several years. It has become evident that a significant challenge in the transition of biomarker candidates to clinical diagnostic assays lies in the development of suitably robust biomarker assays, especially multiplexed assays, and their clinical validation in appropriate patient sample cohorts. Recent developments in mass spectrometry-based targeted quantitative protein measurements have transformed our ability to rapidly develop multiplexed protein biomarker assays. These advances are likely to have a significant impact on the validation of biomarkers in the future. In this review, we have comprehensively compiled a list of candidate biomarkers in rheumatoid and psoriatic arthritis, evaluated the evidence for their potential as biomarkers of bone (joint) damage, and outlined how mass spectrometry-based targeted and multiplexed measurement of candidate biomarker proteins is likely to accelerate their clinical validation and the development of clinical diagnostic tests.

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Section: An Emerging Mass Spectrometry Technologymentioning

confidence: 99%

Early biomarkers of joint damage in rheumatoid and psoriatic arthritis

Ardle¹,

Flatley²,

Pennington³

et al. 2015

Arthritis Res Ther

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“…Serum for LC-MS/MS analysis was prepared by depletion of the 14 most highly abundant proteins using a MARS Hu-14 affinity depletion column (Agilent Technologies, P/N 5188-6557) and visually confirmed using SDS chromatography as previously described 23. Depleted samples were further concentrated by centrifugation and then subjected to in-solution tryptic digestion followed by desalting using C18 zip tips (online supplementary methods S3).…”

Section: Methodsmentioning

confidence: 99%

Molecular signature characterisation of different inflammatory phenotypes of systemic juvenile idiopathic arthritis

et al. 2019

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ObjectivesThe International League of Associations for Rheumatology classification criteria define systemic juvenile idiopathic arthritis (SJIA) by the presence of fever, rash and chronic arthritis. Recent initiatives to revise current criteria recognise that a lack of arthritis complicates making the diagnosis early, while later a subgroup of patients develops aggressive joint disease. The proposed biphasic model of SJIA also implies a ‘window of opportunity’ to abrogate the development of chronic arthritis. We aimed to identify novel SJIA biomarkers during different disease phases.MethodsChildren with active SJIA were subgrouped clinically as systemic autoinflammatory disease with fever (SJIA syst ) or polyarticular disease (SJIA poly ). A discovery cohort of n=10 patients per SJIA group, plus n=10 with infection, was subjected to unbiased label-free liquid chromatography mass spectrometry (LC-MS/MS) and immunoassay screens. In a separate verification cohort (SJIA syst , n=45; SJIA poly , n=29; infection, n=32), candidate biomarkers were measured by multiple reaction monitoring MS (MRM-MS) and targeted immunoassays.ResultsSignatures differentiating the two phenotypes of SJIA could be identified. LC-MS/MS in the discovery cohort differentiated SJIA syst from SJIA poly well, but less effectively from infection. Targeted MRM verified the discovery data and, combined with targeted immunoassays, correctly identified 91% (SJIA syst vs SJIA poly ) and 77% (SJIA syst vs infection) of all cases.ConclusionsMolecular signatures differentiating two phenotypes of SJIA were identified suggesting shifts in underlying immunological processes in this biphasic disease. Biomarker signatures separating SJIA in its initial autoinflammatory phase from the main differential diagnosis (ie, infection) could aid early-stage diagnostic decisions, while markers of a phenotype switch could inform treat-to-target strategies.

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“…Following SRM analysis, it was demonstrated that these 12 proteins could be used to distinguish patients with PsA from those with OA [126]. Other research groups have identified clusters of differentially expressed proteins in synovial fluid and tissues from a wide range of arthritides [127,128]. However, in the context of routine analysis in clinics, it would be more convenient if biomarkers were developed in readily accessible biofluids such as blood or urine.…”

Section: Biomarker Discovery In Psamentioning

confidence: 96%

“…Using this assay, it was possible to detect protein biomarkers predictive of disease recurrence in prostate cancer patients Morriessy et al [128] Ademowo et al developed an MRM assay incorporating 57 proteins measured in synovial tissue. Using this assay, it was possible to distinguish between PsA patients who responded well to therapy from those who did not respond Ademowo et al [125] Cretu et al developed an MRM assay for 47 candidate biomarkers found to be differentially expressed during LC-MS/MS analysis of PsA and psoriasis serum.…”

Section: Mrmmentioning

confidence: 98%

Psoriatic Arthritis Under a Proteomic Spotlight: Application of Novel Technologies to Advance Diagnosis and Management

et al. 2015

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Psoriatic arthritis is a form of inflammatory arthritis that is frequently associated with psoriasis. Individuals with this disease present with heterogeneous clinical manifestations, making it challenging to diagnose and select optimal treatment strategies. Perhaps, not unsurprisingly, there are currently no molecular diagnostic or prognostic tests to confirm if a patient has the disease or predict how they may respond to therapy. Instead, a range of classification criteria have been developed, and the experience of the treating clinician is heavily relied upon. It is therefore widely accepted that there is a significant and as yet unmet need for effective molecular markers in psoriatic arthritis. Protein mediators drive disease pathogenesis and, therefore, represent logical potential biomarkers. Indeed, significant advances have recently been made by the introduction of multiplexed protein biomarker tests for monitoring disease activity in rheumatoid arthritis. At the same time, recent advances in proteomics have enhanced the capabilities for the detection and discovery of protein biomarkers. These advances offer renewed opportunities for the development of multi-protein biomarker signatures to support clinical decision-making in the diagnosis, prognosis and treatment of psoriatic arthritis. This review summarises the pathogenesis of psoriatic arthritis, highlighting specific areas of unmet clinical need. Furthermore, it seeks to illustrate how the latest developments in proteomic technologies could be used to enhance our understanding of the molecular pathology of psoriatic arthritis and improve clinical outcomes and quality of life for patients.

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Development of a label‐free LC‐MS/MS strategy to approach the identification of candidate protein biomarkers of disease recurrence in prostate cancer patients in a clinical trial of combined hormone and radiation therapy

Cited by 19 publications

References 42 publications

Early biomarkers of joint damage in rheumatoid and psoriatic arthritis

Early biomarkers of joint damage in rheumatoid and psoriatic arthritis

Molecular signature characterisation of different inflammatory phenotypes of systemic juvenile idiopathic arthritis

Psoriatic Arthritis Under a Proteomic Spotlight: Application of Novel Technologies to Advance Diagnosis and Management

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