Pásztor Róbert, Viskolcz Béla, Oláh Csaba, Váradi Csaba
Institute of Chemistry, Faculty of Materials and Chemical Engineering, University of Miskolc, 3515 Miskolc, Hungary.
Department of Neurosurgery, Borsod-Abaúj-Zemplén County Center Hospital and University Teaching Hospital, 3526 Miskolc, Hungary.
Int J Mol Sci. 2025 Apr 25;26(9):4105. doi: 10.3390/ijms26094105.
Gynecologic tumors are a leading cause of cancer-related mortality in women worldwide, with endometrial, ovarian, and cervical types being the most prevalent. Aberrant glycosylation, a key post-translational modification, plays a crucial role in tumor development, metastasis, and immune evasion. Specific glycosylation changes, such as altered sialylation and fucosylation, have been identified in gynecologic cancers and are associated with disease progression and prognosis. Understanding glycosylation alterations in gynecologic cancers holds promise for novel diagnostic and therapeutic approaches, ultimately enhancing patient outcomes. In this study, the serum N-glycome was analyzed in patients with myoma uteri, endometriosis, and cervical carcinoma by hydrophilic-interaction liquid chromatography (HILIC-UPLC) with fluorescence (FLR) and mass-spectrometric (MS) detection in order to identify their biomarker potential. Individual serum samples were deglycosylated by PNGase F digestion followed by procainamide labeling and solid-phase-extraction-based purification. All disease groups exhibited consistently higher levels of specific bi-antennary glycans (A2G2 and A2G2S1) compared to control patients. Additionally, significantly higher levels of agalactosylated and mono-sialylated glycans were found in cervical cancer, while a notable decrease in bisected N-glycans, alongside an increase in highly branched tetra-sialylated glycans, was found in endometriosis. Our study serves as proof-of-concept, demonstrating that discovering biomarkers within the serum N-glycome is a promising approach for identifying non-invasive indicators of gynecologic conditions.
妇科肿瘤是全球女性癌症相关死亡的主要原因，其中子宫内膜癌、卵巢癌和宫颈癌最为常见。异常糖基化是一种关键的翻译后修饰，在肿瘤发生、转移和免疫逃逸中起关键作用。在妇科癌症中已发现特定的糖基化变化，如唾液酸化和岩藻糖基化改变，这些变化与疾病进展和预后相关。了解妇科癌症中的糖基化改变有望带来新的诊断和治疗方法，最终改善患者预后。在本研究中，通过亲水相互作用液相色谱（HILIC-UPLC）结合荧光（FLR）和质谱（MS）检测，分析了子宫肌瘤、子宫内膜异位症和宫颈癌患者的血清N-聚糖组，以确定其作为生物标志物的潜力。个体血清样本经PNGase F酶切去糖基化，然后进行普鲁卡因酰胺标记和基于固相萃取的纯化。与对照患者相比，所有疾病组中特定的双触角聚糖（A2G2和A2G2S1）水平均持续较高。此外，在宫颈癌中发现无岩藻糖基化和单唾液酸化聚糖水平显著升高，而在子宫内膜异位症中发现平分型N-聚糖显著减少，同时高度分支的四唾液酸化聚糖增加。我们的研究作为概念验证，表明在血清N-聚糖组中发现生物标志物是识别妇科疾病非侵入性指标的一种有前景的方法。
