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B. Domon

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    P1.06 - Poster Session 1 - Prognostic and Predictive Biomarkers (ID 161)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P1.06-017 - Targeted proteomics and HT-IHC for lung cancer biomarker studies. (ID 1658)

      09:30 - 16:30  |  Author(s): B. Domon

      • Abstract

      Lung cancer is the leading cause of cancer-related death in Luxembourg with high metastatic potential and mortality rate. Despite tremendous efforts made in biomarker studies for this disease, none of the blood-based tests available in the clinic are able to detect the presence of lung cancer early enough or to predict outcome in patients subjected to targeted treatments. Analytical difficulties of plasma proteome due to the high complexity and large dynamic range, and the lack of accessibility to the high-quality clinical samples are major obstacles, requiring a strategic and efficient experiment design to develop potent diagnostic and predictive/prognostic biomarkers.

      In this study, liquid chromatography-mass spectrometry (LC-MS) based targeted proteomics and high-throughput immunohistochemistry (HT-IHC) screening were applied to plasma and tissue samples derived from the matching patients in order to identify lung cancer biomarkers detectable in plasma. A total of 95 biomarker candidates potentially secreted or shed to blood were selected from the previously performed discovery studies. Two proteotypic peptides per target were selected as surrogate peptides and selected reaction monitoring (SRM) based LC-MS assays for 190 peptides were developed. The evaluated assays were multiplexed in two LC-MS methods and analyzed in depleted plasma samples of lung cancer patients. For HT-IHC, tissue micro arrays (TMAs) of matching patients were prepared from formalin fixed and paraffin embedded (FFPE) blocks acquired during the surgery of the patients whose plasma samples were used for proteomic analyses. Both tumor and adjacent non tumor area of the FFPE blocks were included in the TMAs and screened against 50 potential biomarkers.

      The complementary results of LC-MS based assays and HT-IHC were analyzed to find the correlation of the expression profiles of targets found in tumor tissues and plasma samples. Several targets in the IHC experiment exhibited significant scores in tumor compared adjacent normal. 17 plasma proteins were analyzed in the corresponding patients’ plasma samples to identify a panel of biomarkers. This panel of biomarkers were further used to monitor the responsiveness of tumors upon therapeutic and surgical interventions.

      Targeted proteomics was successfully applied to lung cancer biomarker study in plasma samples. Expression profiles of cellular protein markers measured by HT-IHC were critical to group the patient samples to be analyzed. A panel of biomarkers is currently being tested as diagnostic, predictive, or prognostic markers in lung cancer, and preliminary results will be shown.