Lin Monica, Seeley Erin H, Ledet Suzanne, Salazar Christina, Breen Michael T, Eberlin Livia S
Department of Chemistry, The University of Texas at Austin, Austin, TX, USA.
Department of Pathology, Ascension Seton Medical Center, Austin, TX, USA.
Anal Bioanal Chem. 2025 Jun 18. doi: 10.1007/s00216-025-05930-z.
Endometriosis is a gynecological condition characterized by the uncontrolled growth of endometrial-like tissue outside the uterine cavity. Although highly prevalent, the biological mechanisms of endometriosis are poorly understood, and the disease is often misdiagnosed due to the unavailability of pre-operative diagnostic methods. Thus, better characterization of molecular markers of endometriosis is critical to improve our understanding of the disease and management of patients. Here, we used matrix-assisted laser desorption ionization mass spectrometry (MALDI MS) imaging to investigate protein and N-glycan molecular signatures in eutopic endometrium and endometriosis lesions from tissues prospectively collected from patients. MALDI MS imaging of intact proteins revealed neutrophil defensins detected at higher relative abundances in regions of endometriosis lesions, providing evidence that immune/inflammatory processes may be associated with endometriosis. Various alterations in N-glycan molecular profiles were also observed when comparing endometriosis lesions and eutopic endometrium, including a significantly higher detection of fucosylated N-glycans and increased levels of branching from biantennary to tri- and tetra-antennary structures in endometriosis lesions. These results provide evidence that alterations in N-glycosylation machinery are involved in dysregulation of cellular and signaling processes and may contribute to endometriosis development. A co-localization analysis identified several tryptic peptides detected within regions of endometriosis lesions, suggesting extracellular matrix (ECM) proteins such as collagen may contribute to the development of endometriosis lesions. Overall, by characterizing molecular alterations in proteins and N-glycans, the results of this study provide novel insights into potential mechanisms involved in endometriosis pathogenesis.
子宫内膜异位症是一种妇科疾病，其特征是子宫腔外出现类似子宫内膜组织的不受控制的生长。尽管该疾病非常普遍，但人们对其生物学机制了解甚少，并且由于缺乏术前诊断方法，该病常常被误诊。因此，更好地表征子宫内膜异位症的分子标志物对于增进我们对该疾病的理解以及患者的管理至关重要。在此，我们使用基质辅助激光解吸电离质谱（MALDI MS）成像技术，对前瞻性收集的患者组织中的在位子宫内膜和子宫内膜异位症病变中的蛋白质和N-聚糖分子特征进行研究。完整蛋白质的MALDI MS成像显示，在子宫内膜异位症病变区域检测到相对丰度较高的中性粒细胞防御素，这表明免疫/炎症过程可能与子宫内膜异位症有关。在比较子宫内膜异位症病变和在位子宫内膜时，还观察到N-聚糖分子谱的各种变化，包括在子宫内膜异位症病变中岩藻糖基化N-聚糖的检测显著增加，以及从双天线结构到三天线和四天线结构的分支水平增加。这些结果提供了证据，表明N-糖基化机制的改变参与了细胞和信号传导过程的失调，并可能促成子宫内膜异位症的发展。共定位分析确定了在子宫内膜异位症病变区域内检测到的几种胰蛋白酶肽段，表明细胞外基质（ECM）蛋白如胶原蛋白可能促成子宫内膜异位症病变发展。总体而言，通过表征蛋白质和N-聚糖中的分子变化，本研究结果为子宫内膜异位症发病机制中潜在的机制提供了新的见解。
