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
    Mittal, Parul ; Klingler-Hoffmann, Manuela ; Arentz, Georgia ; Winderbaum, Lyron ; Kaur, Gurjeet ; Anderson, Lyndal ; Scurry, James ; Leung, Yee ; Stewart, Colin J. R. ; Carter, Jonathan ; Hoffmann, Peter ; Oehler, Martin K. / Annexin A2 and alpha actinin 4 expression correlates with metastatic potential of primary endometrial cancer. In: BBA: Proteins and Proteomics. 2017 ; Vol. 1865, No. 7. pp. 846-857.
    @article{5041bdb6cf494156a0436f76fa6e1ff5,
    title = "Annexin A2 and alpha actinin 4 expression correlates with metastatic potential of primary endometrial cancer",
    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.",
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    author = "Parul Mittal and Manuela Klingler-Hoffmann and Georgia Arentz and Lyron Winderbaum and Gurjeet Kaur and Lyndal Anderson and James Scurry and Yee Leung and Stewart, {Colin J. R.} and Jonathan Carter and Peter Hoffmann and Oehler, {Martin K.}",
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    Mittal, P, Klingler-Hoffmann, M, Arentz, G, Winderbaum, L, Kaur, G, Anderson, L, Scurry, J, Leung, Y, Stewart, CJR, Carter, J, Hoffmann, P & Oehler, MK 2017, 'Annexin A2 and alpha actinin 4 expression correlates with metastatic potential of primary endometrial cancer' BBA: Proteins and Proteomics, vol. 1865, no. 7, pp. 846-857. https://doi.org/10.1016/j.bbapap.2016.10.010

    Annexin A2 and alpha actinin 4 expression correlates with metastatic potential of primary endometrial cancer. / Mittal, Parul; Klingler-Hoffmann, Manuela; Arentz, Georgia; Winderbaum, Lyron; Kaur, Gurjeet; Anderson, Lyndal; Scurry, James; Leung, Yee; Stewart, Colin J. R.; Carter, Jonathan; Hoffmann, Peter; Oehler, Martin K.

    In: BBA: Proteins and Proteomics, Vol. 1865, No. 7, 07.2017, p. 846-857.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Annexin A2 and alpha actinin 4 expression correlates with metastatic potential of primary endometrial cancer

    AU - Mittal, Parul

    AU - Klingler-Hoffmann, Manuela

    AU - Arentz, Georgia

    AU - Winderbaum, Lyron

    AU - Kaur, Gurjeet

    AU - Anderson, Lyndal

    AU - Scurry, James

    AU - Leung, Yee

    AU - Stewart, Colin J. R.

    AU - Carter, Jonathan

    AU - Hoffmann, Peter

    AU - Oehler, Martin K.

    PY - 2017/7

    Y1 - 2017/7

    N2 - 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.

    AB - 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.

    KW - Endometrial cancer

    KW - Metastasis

    KW - Annexin A2

    KW - a actinin 4

    KW - MALDI MSI

    KW - Label free LC-MS/MS

    KW - LYMPH-NODE METASTASIS

    KW - TISSUE MICROARRAY ANALYSIS

    KW - FACTOR RECEPTOR EXPRESSION

    KW - GYNECOLOGIC-ONCOLOGY-GROUP

    KW - IMAGING MASS-SPECTROMETRY

    KW - BREAST-CANCER

    KW - PROSTATE-CANCER

    KW - GENE-EXPRESSION

    KW - GASTRIC-CANCER

    KW - OVARIAN-CANCER

    U2 - 10.1016/j.bbapap.2016.10.010

    DO - 10.1016/j.bbapap.2016.10.010

    M3 - Article

    VL - 1865

    SP - 846

    EP - 857

    JO - Biochimica et Biophysica Acta - Proteins and Proteomics

    JF - Biochimica et Biophysica Acta - Proteins and Proteomics

    SN - 1570-9639

    IS - 7

    ER -