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Tissue proteome analysis revealed an association between cancer, immune system response, and the idiopathic granulomatous mastitis

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Abstract

Idiopathic Granulomatous Mastitis (IGM) is a disease that clinically mimics breast cancers with symptoms of pain, edema, erythema, nipple discharge, nipple retraction, and fistula. Although IGM is considered to be formed by autoimmune responses or infections, the molecular mechanism behind formation and progress is unknown. Therefore, in this study, we aimed to investigate molecular mechanisms underlying IGM formation, progress, and recurrence by monitoring the changes at the proteome level. Protein extracts prepared from IGM (n = 15) and within-control tissues (n = 15) were subjected to nHPLC followed by LC–MS/MS proteomic analysis. Label-free quantitation analysis revealed that sixty differentially regulated between the two groups. Those proteins were classified based on their role in metabolic pathways using bioinformatics tools. Based on DAVID analysis, 16 of the differently regulated proteins were associated with the immune system, while 17 proteins were involved in cancer metabolism. STRING analysis showed that five of the differentially regulated proteins were associated with combined immune deficiency which were PNP, TAP1, ITGAL, PRKDC, and PTPRC while the other proteins were involved in insulin response and neutrophil degranulation. This study is one of the very few studies that investigated the changes in protein expressions of IGM tissues compared to controls. For the first time, we have shown the relationship of IGM with the immune system at the protein level and also underlined the cancer-like behavior of the disease. Furthermore, the proteins that were pointed out as combined immune deficiency-related proteins may have value as diagnostic markers for idiopathic granulomatous mastitis although further studies are needed to shed more light on the pathogenesis of the disease.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

This study was supported by Kocaeli University Scientific Research Projects Coordination Unit under Grant no. 2019/092.

Funding

This study was supported by Kocaeli University Scientific Research Projects Coordination Unit under Grant no. 2019/092.

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Authors and Affiliations

  1. Department of Medical Biology, Medical School, Kocaeli University, 41001, Kocaeli, Turkey

    Merve Gulsen Bal Albayrak, Murat Kasap & Gurler Akpinar

  2. Department of General Surgery, Medical School, Kocaeli University, 41001, Kocaeli, Turkey

    Turgay Simsek, Nuh Zafer Canturk & Sertac Ata Guler

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  1. Merve Gulsen Bal Albayrak
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Contributions

Study conception and experimental design were performed by MGBA, MK, and GA. Tissue collection with surgeries and storage were performed by TS, ZC, and SAG. Sample preparation and protein isolation were performed by MGBA and TŞ. Western Blot analysis, LC–MS/MS analysis and MS analysis were performed by MGB, MK, and GA. Bioinformatic analysis were performed by MGBA and GA. The first draft of the manuscript was written by MGBA. Writing, review, and editing the draft were performed by GA and MK. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Gurler Akpinar.

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The authors have no relevant financial or non-financial interests to disclose.

Ethical approval

The Kocaeli University Ethics Committee has approved this work (approval numbers: KU GOKAEK-2019/16.05 2019/140). To protect the human subjects and maintain high ethical standards, Declaration of Helsinki was followed. All patients provided their written informed consents, and all the procedures were performed at Kocaeli University Hospital.

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Informed consents, approved by the ethics committee, were acquired from each patient.

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Albayrak, M.G.B., Simsek, T., Kasap, M. et al. Tissue proteome analysis revealed an association between cancer, immune system response, and the idiopathic granulomatous mastitis. Med Oncol 39, 238 (2022). https://doi.org/10.1007/s12032-022-01845-2

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