Detection of oesophageal cancer biomarkers by plasma proteomic profiling of human cell line xenografts in response to chemotherapy

Peter Kelly, V. Appleyard, K. Murray, F. Paulin, D. Lamont, L. Baker, S. Suttie, D. Exon, A. Thompson

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    Abstract

    BACKGROUND: The incidence of oesophageal adenocarcinoma is increasing worldwide but survival remains poor. Neoadjuvant chemotherapy may improve survival, but targeting treatment to patients who respond to chemotherapy could be improved by the availability of markers of response. This study sought proteomic markers of therapeutic response using an adenocarcinoma xenograft model.

    METHODS: Epirubicin, cisplatin or 5-fluorouracil was administered to severe combined immune-deficient mice bearing OE19 oesophageal adenocarcinoma xenografts. Murine plasma samples from treated and untreated xenografts were analysed by surface-enhanced laser desorption/ionisation time-of-flight mass spectroscopy, and panels of peaks were found using class prediction models that distinguished treatment groups. Proteins in these peaks were identified by mass spectroscopy in tryptic digests of purified fractions. Five paired samples from oesophageal cancer patients before and after chemotherapy were analysed using the same methodology.

    RESULTS: Plasma protein peaks were identified that differed significantly (P<0.05, ANOVA) between the treated xenograft and control groups. Marker panels predicted treated vs untreated xenografts with sensitivities of 100%, specificities of 86-100% and test efficiencies of 89-100%. Three of the proteins identified in these panels, apolipoprotein A-I, serum amyloid A and transthyretin were confirmed in the clinical samples.

    CONCLUSION: Plasma protein markers can be detected in response to chemotherapy in oesophageal adenocarcinoma xenografts and in clinical samples, and have the potential to monitor response and guide chemotherapy in oesophageal adenocarcinoma. British Journal of Cancer (2010) 103, 232-238. doi: 10.1038/sj.bjc.6605741 www.bjcancer.com Published online 15 June 2010 (C) 2010 Cancer Research UK

    Original languageEnglish
    Pages (from-to)232-238
    Number of pages7
    JournalBritish Journal of Cancer
    Volume103
    Issue number2
    DOIs
    Publication statusPublished - 13 Jul 2010

    Keywords

    • oesophageal adenocarcinoma
    • response to chemotherapy
    • proteomics
    • biomarkers
    • FLIGHT MASS-SPECTROMETRY
    • HEMOGLOBIN LEVEL
    • TUMOR-REGRESSION
    • STAGING SYSTEM
    • PROTEIN
    • CARCINOMA
    • ADENOCARCINOMA
    • SURVIVAL
    • MARKERS
    • CHEMORADIOSENSITIVITY

    Cite this

    Kelly, P., Appleyard, V., Murray, K., Paulin, F., Lamont, D., Baker, L., Suttie, S., Exon, D., & Thompson, A. (2010). Detection of oesophageal cancer biomarkers by plasma proteomic profiling of human cell line xenografts in response to chemotherapy. British Journal of Cancer, 103(2), 232-238. https://doi.org/10.1038/sj.bjc.6605741