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C. Caviezel

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    P1.02 - Biology/Pathology (ID 614)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Biology/Pathology
    • Presentations: 1
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      P1.02-005 - SolvingĀ the Interfering Problem of Tissue Embedding OCT Compound in Activity Based Multiplex Profiling of Tyrosine Kinase Substrates (ID 9485)

      09:30 - 16:00  |  Author(s): C. Caviezel

      • Abstract

      The analysis of clinically relevant human tissue preserved in optimal cutting temperature (OCT) medium with activity based proteomic approaches are promising for the discovery of novel druggable disease biomarkers for the diagnosis, prognosis and prediction of response to therapeutic interventions. Nonetheless, and for many different proteomic approaches, there are important signal interferences observed in the presence of the OCT compound.

      We tested activity based multiplex profiling tyrosine kinase substrates in a large batch of neoplastic and non-neoplastic lung resection specimen embedded with or without OCT. Since January 2003 we collected fresh frozen matched pairs from malignant adenocarcinoma and non-neoplastic lung biopsies. In 2007, we started to embedded all our samples in OCT. We obtained all clinical characteristics of 47 patients with early TNM stage 1 lung adenocarcinoma. We observed significant differences in overall phosphorylation levels and searched for reasons explaining such a large effect.

      We ruled out the implication of either short versus long storage time after sample extraction or of nonhomogeneous batch processing of samples. We documented that the clear downward shift in overall phosphorylation levels coincided with the introduction of OCT as an improved embedding medium for resection specimen. For all the kinomes extracted, we developed a corrective procedure where a median centering was performed on the values of each peptide, separately for the with or without OCT samples.

      We applied corrective filtering of data to the multiplex profiling approach of well characterised tyrosine kinase substrates obtained in lung resection specimen embedded with or without OCT. With the OCT correction parameters applied, the quantitation of molecular prognosis signature based on tyrosine kinase activity differences found in lung adenocarcinoma resection specimens may result in the identification of novel targets for future anti-lung cancer therapies.