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pmid:28117336
CD5 molecule-like and transthyretin as putative biomarkers of chronic myeloid leukemia - an insight from the proteomic analysis of human plasma.
Iram Fatima · Saima Sadaf · Syed Ghulam Musharraf · Naghma Hashmi · Muhammad Waheed Akhtar
Scientific reports · 2017 doi:10.1038/srep40943
Paper
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Experiment
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Data
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Analysis
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Execution
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Complete file
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Aim of this study was to identify the candidate circulating markers of chronic-phase chronic myeloid leukemia (CP-CML) manifestations, having potential to develop into predictive- or monitoring-biomarkers. A proteomic approach, two-dimensional gel electrophoresis in conjunction with mass spectrometry (2DE-MS), was employed for this purpose. Based on the spot intensity measurements, six proteins were found to be consistently dysregulated in CP-CML subjects compared to the healthy controls [false discovery rate (FDR) threshold ≤0.05]. These were identified as α-1-antichymotrypsin, α-1-antitrypsin, CD5 molecule-like, stress-induced phosphoprotein 1, vitamin D binding protein isoform 1 and transthyretin by MS analysis [PMF score ≥79; data accessible via ProteomeXchange with identifier PXD002757]. Quantitative ELISA, used for validation of candidate proteins both in the pre-treated and nilotinib-treated CP-CML cases, demonstrate that CD5 molecule-like, transthyretin and alpha-1-antitrypsin may serve as useful predictive markers and aid in monitoring the response of TKI-based therapy (ANOVA p < 0.0001). Two of the circulating marker proteins, identified in this study, had not previously been associated with chronic- or acute-phase myeloid leukemia. Exploration of their probable association with CP-CML, in a larger study cohort, may add to our understanding of the disease mechanism besides developing clinically useful biomarkers in future.", "claims": [{"id": "claim-method", "statement": "The spot intensity differences obtained from the 2D-gel images of at least 3 different sets of independent plasma samples were analyzed by non-parametric Mann-Whitney U test.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:28117336", "locator": "sections[14] \"Statistical analysis and validation of biomarker candidates\" paragraph 2", "quote": "The spot intensity differences obtained from the 2D-gel images of at least 3 different sets of independent plasma samples were analyzed by non-parametric Mann-Whitney U test."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The proteomics data was deposited to the ProteomeXchange Consortium8 via PRIDE partner repository (http://www.ebi.ac.uk/pride/) with the dataset identifier PXD002757.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:28117336", "locator": "sections[5] \"2D proteome profiling and mass spectrometric analysis\" paragraph 2", "quote": "The proteomics data was deposited to the ProteomeXchange Consortium8 via PRIDE partner repository (http://www.ebi.ac.uk/pride/) with the dataset identifier PXD002757."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The study used two-dimensional gel electrophoresis with mass spectrometry (2DE-MS), identified differentially expressed proteins using a false discovery rate threshold ≤0.05 and peptide mass fingerprinting score ≥79, and made the proteomics data accessible through ProteomeXchange under identifier PXD002757.", "kind": "quantitative", "target": {"value": 0.0001, "unit": "p-value", "tolerance": null, "source": "Quantitative ELISA, used for validation of candidate proteins both in the pre-treated and nilotinib-treated CP-CML cases, demonstrate that CD5 molecule-like, transthyretin and alpha-1-antitrypsin may serve as useful predictive markers and aid in monitoring the response of TKI-based therapy (ANOVA p < 0.0001)."}, "evidence": [{"asset": "source:pmid:28117336", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "A proteomic approach, two-dimensional gel electrophoresis in conjunction with mass spectrometry (2DE-MS), was employed for this purpose."}, {"asset": "source:pmid:28117336", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Based on the spot intensity measurements, six proteins were found to be consistently dysregulated in CP-CML subjects compared to the healthy controls [false discovery rate (FDR) threshold ≤0.05]."}, {"asset": "source:pmid:28117336", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "These were identified as α-1-antichymotrypsin, α-1-antitrypsin, CD5 molecule-like, stress-induced phosphoprotein 1, vitamin D binding protein isoform 1 and transthyretin by MS analysis [PMF score ≥79; data accessible via ProteomeXchange with identifier PXD002757]."}, {"asset": "source:pmid:28117336", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Quantitative ELISA, used for validation of candidate proteins both in the pre-treated and nilotinib-treated CP-CML cases, demonstrate that CD5 molecule-like, transthyretin and alpha-1-antitrypsin may serve as useful predictive markers and aid in monitoring the response of TKI-based therapy (ANOVA p < 0.0001)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "The study used two-dimensional gel electrophoresis with mass spectrometry (2DE-MS), identified differentially expressed proteins using a false discovery rate threshold ≤0.05 and peptide mass fingerprinting score ≥79, and made the proteomics data accessible through ProteomeXchange under identifier PXD002757.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:28117336"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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