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J. Creaney



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    New approaches in rare thoracic tumors (ID 60)

    • Event: ELCC 2018
    • Type: Proffered Paper session
    • Track:
    • Presentations: 1
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      214O - Multiplexed proteomics biomarkers for malignant pleural mesothelioma detection in blood (ID 385)

      11:00 - 12:30  |  Author(s): J. Creaney

      • Abstract
      • Slides

      Background:
      Blood biomarkers are not routinely applied for the diagnosis of malignant pleural mesothelioma (MPM). We investigated a multiplexed biomarkers signature composed of 6 glycopeptides for the diagnosis of MPM in blood using mass spectrometry based targeted proteomics.

      Methods:
      We applied the targeted proteomics technology selected reaction monitoring (SRM, also known as multiple reaction monitoring – MRM) to investigate more than 400 serum samples from early and advanced stages MPM patients and asbestos exposed donors. Samples were from biobanks in the USA, Australia and Europe. Samples were enriched for N-linked glycoproteins using hydrazide chemistry. After tryptic digestion, N-linked glycopeptides were separated by liquid chromatography before analysis on a triple quadrupole mass spectrometer (LC-MS/MS). Logistic regression was fitted on a training set of 212 samples followed by evaluation of predictive accuracy of the signature in a validation set of 193 samples.

      Results:
      The proteomics platform for serum processing on 96-well plates and LC-MS/MS analysis had coefficient of variation between 2.0 and 11.4% for peptide quantification over more than 700 measurements, and standard deviation of 0.42 for processing more than 400 replicates. The predictive accuracy for MPM discrimination was significantly higher using multiplexed biomarkers by mass spectrometry compared to using single biomarkers alone. The multiplexed proteomics signature separated MPM patients and asbestos exposed donors with an area under the receiver operating characteristic curve (AUC) of 0.72 in the validation set, and AUC for discriminating early stage MPM from asbestos exposed donors was 0.74. Predictive accuracy of the proteomics signature was not inferior to the currently best available MPM blood biomarker soluble-mesothelin related peptides (SMRP) measured in the samples of the validation set using an enzyme-linked immunosorbent assay (ELISA) approved by the US food and drug administration (FDA). Furthermore, signature was significantly associated with survival of MPM patients after treatment.

      Conclusions:
      Mass spectrometry based proteomics biomarkers have potential for MPM diagnosis in blood.

      Clinical trial identification:


      Legal entity responsible for the study:
      The Ohio State University Medical Center

      Funding:
      Kathy and Jay Worly Lung Cancer Early Detection Fund Don Ward, President, Special Claims Services, Inc. at The Ohio State University Comprehensive Cancer Center (OSUCCC) The Swiss National Science Foundation (postdoc mobility fellowship)

      Disclosure:
      All authors have declared no conflicts of interest.

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