Chen Dayong, Zhou Ling, Qiao Hai, Wang Yiting, Xiao Yao, Fang Liaoqiong, Yang Bing, Wang Zhibiao
State Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing 400016, P.R. China.
Department of Obstetrics and Gynecology, The Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563000, P.R. China.
Exp Ther Med. 2022 Jun;23(6):374. doi: 10.3892/etm.2022.11301. Epub 2022 Apr 7.
Extracellular vesicles (EVs) carry specific proteins involved in intercellular communication. EVs with different protein contents are released into circulation in different diseases. Recent studies have identified proteins in adenomyosis (AM)-derived EVs (AMEVs) from blood as biomarkers for this disease. AM is an extension of endometrial tissue into the uterine myometrium. Magnetic resonance imaging (MRI) is the most accurate imaging tool for identifying adenomyosis. Therefore, the present study aimed to investigate the role of EVs in diagnosing AM. In the present study, tissue AMEVs (T-AMEVs) were isolated from lesion homogenates of patients with adenomyosis, and blood AMEVs (B-AMEVs) were isolated from peripheral blood of patients with AM via differential centrifugation and density gradient centrifugation. T-AMEVs and B-AMEVs were characterized by electron microscopy, western blotting and mass spectrometry and analysed using FunRich3.1.3 software. T-AMEVs (average diameter, 150.9±102.2 nm) and B-AMEVs (194.1±66.81 nm) expressed the CD9, CD63 and flotillin-2 EV markers. A total of 211 proteins expressed in T-AMEVs and B-AMEVs overlapped with Vesiclepedia database entries, including 2 epithelial-to-mesenchymal transition (EMT)-associated proteins and 6 invasion-associated proteins. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that these 211 proteins were associated with the 'regulation of cell morphogenesis' and 'cytoskeletal organization' terms, as well as the PPAR and HIF-1 signalling pathways, which are related to the proliferation and metastasis of endometrial cells that cannot invade the myometrium under normal circumstances. Among the 211 proteins, HSP90A, STIP1 and TAGLN-2 were expressed in T-AMEVs and B-AMEVs, but not in serum EVs of women without adenomyosis/endometriosis, and these proteins might be the potential biomarkers for adenomyosis. These findings provide insights into the molecular features of adenomyosis and the new candidate biomarkers for diagnosis.
细胞外囊泡（EVs）携带参与细胞间通讯的特定蛋白质。不同蛋白质含量的EVs在不同疾病中释放到循环系统中。最近的研究已将血液中来自子宫腺肌病（AM）的EVs（AMEVs）中的蛋白质鉴定为该疾病的生物标志物。子宫腺肌病是子宫内膜组织向子宫肌层的延伸。磁共振成像（MRI）是识别子宫腺肌病最准确的成像工具。因此，本研究旨在探讨EVs在子宫腺肌病诊断中的作用。在本研究中，通过差速离心和密度梯度离心从子宫腺肌病患者的病变匀浆中分离出组织AMEVs（T-AMEVs），并从子宫腺肌病患者的外周血中分离出血液AMEVs（B-AMEVs）。通过电子显微镜、蛋白质印迹法和质谱对T-AMEVs和B-AMEVs进行表征，并使用FunRich3.1.3软件进行分析。T-AMEVs（平均直径，150.9±102.2 nm）和B-AMEVs（194.1±66.81 nm）表达CD9、CD63和flotillin-2 EV标志物。共有211种在T-AMEVs和B-AMEVs中表达的蛋白质与Vesiclepedia数据库条目重叠，其中包括2种上皮-间质转化（EMT）相关蛋白和6种侵袭相关蛋白。基因本体论和京都基因与基因组百科全书（KEGG）通路分析表明，这211种蛋白质与“细胞形态发生调控”和“细胞骨架组织”术语以及PPAR和HIF-1信号通路相关，这些通路与在正常情况下无法侵入肌层的子宫内膜细胞的增殖和转移有关。在这211种蛋白质中，HSP90A、STIP1和TAGLN-2在T-AMEVs和B-AMEVs中表达，但在无子宫腺肌病/子宫内膜异位症女性的血清EVs中不表达，这些蛋白质可能是子宫腺肌病的潜在生物标志物。这些发现为子宫腺肌病的分子特征和新的诊断候选生物标志物提供了见解。
