Annexin A2 and alpha actinin 4 expression correlates with metastatic potential of primary endometrial cancer

Parul Mittal, Manuela Klingler-Hoffmann, Georgia Arentz, Lyron Winderbaum, Gurjeet Kaur, Lyndal Anderson, James Scurry, Yee Leung, Colin J. R. Stewart, Jonathan Carter, Peter Hoffmann, Martin K. Oehler

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    Abstract

    The prediction of lymph node metastasis using clinic-pathological data and molecular information from endometrial cancers lacks accuracy and is therefore currently not routinely used in patient management. Consequently, although only a small percentage of patients with endometrial cancers suffer from metastasis, the majority undergo radical surgery including removal of pelvic lymph nodes. Upon analysis of publically available data and published research, we compiled a list of 60 proteins having the potential to display differential abundance between primary endometrial cancers with versus those without lymph node metastasis. Using data dependent acquisition LC-ESI-MS/MS we were able to detect 23 of these proteins in endometrial cancers, and using data independent LC-ESI-MS/MS the differential abundance of five of those proteins was observed. The localization of the differentially expressed proteins, was visualized using peptide MALDI MSI in whole tissue sections as well as tissue microarrays of 43 patients. The proteins identified were further validated by immunohistochemistry. Our data indicate that annexin A2 protein level is upregulated, whereas annexin Al and a actinin 4 expression are downregulated in tumours with lymph node metastasis compared to those without lymphatic spread. Moreover, our analysis confirmed the potential of these markers, to be included in a statistical model for prediction of lymph node metastasis. The predictive model using highly ranked m/z values identified by MALDI MSI showed significantly higher predictive accuracy than the model using immunohistochemistry data. In summary, using publicly available data and complementary proteomics approaches, we were able to improve the prediction model for lymph node metastasis in EC. (C) 2016 Elsevier B.V. All rights reserved.

    Original languageEnglish
    Pages (from-to)846-857
    Number of pages12
    JournalBBA: Proteins and Proteomics
    Volume1865
    Issue number7
    DOIs
    Publication statusPublished - Jul 2017

    Cite this

    Mittal, P., Klingler-Hoffmann, M., Arentz, G., Winderbaum, L., Kaur, G., Anderson, L., ... Oehler, M. K. (2017). Annexin A2 and alpha actinin 4 expression correlates with metastatic potential of primary endometrial cancer. BBA: Proteins and Proteomics, 1865(7), 846-857. https://doi.org/10.1016/j.bbapap.2016.10.010