Identification of biomarkers for drug-resistant endometriosis using clinical proteomics

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Proteomics identified proteins related to neutrophil activation and inflammation, including azurocidin, in drug-resistant endometriosis cases compared to sensitive ones.

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This paper investigated the mechanisms underlying resistance to the progestin dienogest (DNG) in a subset of endometriotic cases by performing clinical proteomics comparing protein expression profiles in DNG-sensitive versus DNG-resistant endometriotic cyst fluid. Proteins associated with neutrophil/granulocyte activation (e.g., myeloperoxidase, lactotransferrin) and inflammatory processes (including azurocidin and neutrophil gelatinase-associated lipocalin) were identified as extracted candidate markers, with azurocidin highlighted as potentially important due to its protease activity related to insulin-like growth factor-1 signaling. A major limitation explicitly acknowledged in the text is that the authors mainly identify and propose biomarkers, calling for further investigation rather than establishing causal mechanisms. This paper is centrally about endometriosis — it identifies proteomic biomarkers linked to dienogest-resistant endometriotic cysts and implicates inflammation-related proteins (especially azurocidin) in resistance-related biology and possible carcinogenesis of endometrioma.

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Abstract

Dienogest (DNG), is an effective and widely used progestin used in the treatment of endometriosis, yet clinically, a subset of cases show resistance to DNG treatment. During a previous investigation on the effect of DNG of cytokines and growth factor production, we incidentally found that endometriotic cyst fluid did not demonstrate inhibitory effects to DNG in a subset of cases. To clarify the mechanisms of this resistance to DNG, we performed proteomics analysis to compare the protein expression between DNG-sensitive and resistant cases. Based upon our results, several proteins were extracted that relate to neutrophil granulocyte activation marker (myeloperoxidase, lactotransferrin), inflammation (azurocidin, neutrophil gelatinase-associated lipocalin, etc.), and others biological processes reflecting the clinical environment of the endometriotic cyst. Among these proteins, azurocidin (AZU) is perhaps most interesting one as azurocidin is a protease that cleaves insulin-like growth factor-1 (IGFBP-1) associated with clear cell carcinoma of the ovary. We propose that the proteins extracted in the present study warrant further investigation in their relationship to carcinogenesis of endometrioma. Similar content being viewed by others

References

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Acknowledgement

This work was supported by JSPS KAKENHI Grant Number 18K09236. Author information Authors and Affiliations Corresponding author Ethics declarations Conflict of interest There is no conflict of interest about this study. Ethical approval This study was approved by the institutional review board (673-02; Faculty of Medicine Research Ethics Committee, Kyorin University). Additional information Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Rights and permissions About this article Cite this article Kobayashi, Y., Fukutomi, T., Mita, S. et al. Identification of biomarkers for drug-resistant endometriosis using clinical proteomics. Human Cell 34, 394–399 (2021). https://doi.org/10.1007/s13577-020-00465-0 Received: Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s13577-020-00465-0

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mesh:D004715endometriosis

MeSH descriptors

Antimicrobial Cationic Peptides Blood Proteins Drug Resistance Endometriosis Endometriosis Nandrolone Proteomics Antimicrobial Cationic Peptides Antimicrobial Cationic Peptides Antimicrobial Cationic Peptides Blood Proteins Blood Proteins Blood Proteins Carcinogenesis Carcinogenesis Cell Line Drug Resistance Endometriosis Endometriosis Endometriosis

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