Tandem mass tag-based quantitative proteomic profiling of the serum of patients with abnormal uterine bleeding associated with copper intrauterine device.

OBJECTIVE To investigate changes in the level of protein in serum and uncover the underlying pathogenesis of abnormal uterine bleeding (AUB) associated with copper intrauterine devices (Cu IUD). METHODS Protein profiles were investigated via tandem mass tag (TMT)-based quantitative proteomics and bioinformatics technology. Quantification and characterization of candidate proteins were further performed in 33 controls and 45 cases by Luminex assay and enzyme-linked immunosorbent assay. RESULTS In total, 842 proteins were identified via TMT coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) in the serum of individuals with IUDs. Among them, 25 differentially expressed proteins (p < 0.05) were observed, including eight upregulated proteins and 17 downregulated proteins. Ten proteins were verified, and Alpha-1-Antitrypsin (a1AT) had a significantly elevated expression in women with AUB associated with the Cu IUD compared with healthy controls (p = 0.026) and a high area under the curve value (0.656), as well as sensitivity (64.9%) and specificity (71.9%). CONCLUSION This is the first study to explore changes in serum protein and the underlying mechanisms of AUB associated with the Cu IUD via TMT technology. a1AT with biomarker potential was validated. These findings might provide an experimental basis for the early diagnosis or treatment of AUB associated with the Cu IUD.