Key Laboratory of Marine Drugs, Ministry of Education, School of Medicine and Pharmacy, Shandong Provincial Key Laboratory of Glycoscience and Glycotechnology , Ocean University of China , Qingdao 266003 , China.
Laboratory for Marine Drugs and Bioproducts , Qingdao National Laboratory for Marine Science and Technology , Qingdao 266003 , China.
J Proteome Res. 2019 Jun 7;18(6):2559-2570. doi: 10.1021/acs.jproteome.9b00073. Epub 2019 Apr 2.
Aberrant protein glycosylation is observed in the progression of many types of diseases, including different cancers. In this study, we assess differential N-glycan patterns of human breast cancer cells and tissues by PGC-ESI-MS/MS. Compared with mammary epithelial cells, high-mannose glycans were significantly elevated in breast cancer cells. However, the alteration of N-glycans in tissues was more obvious than that in cells. Sixty-three kinds of different N-glycans were stably identified, and 38 types of them exhibited significant differences between para-carcinoma and breast cancer tissues. High-mannose glycans and core-fucosylated glycans were increased in the breast cancer tissues, while bisected glycans and sialylated glycans were decreased. Moreover, a total of 27 types of N-glycans displayed evident differences between benign breast tumor and breast cancer tissues, and most of them including bisected and sialylated glycans exhibited decreased relative abundances in cancer tissues. Overall, three high-mannose N-glycans (F0H6N2S0, F0H7N2S0, F0H8N2S0) exhibited significant diagnostic accuracy in both breast cancer cells and tissues, suggesting their potential role in biomarkers. Furthermore, a negative correlation between sialylated glycans and age of patients was identified. In conclusion, our results may be beneficial to understand the role that N-glycan plays on the progression of breast cancer and propose potential diagnostic biomarkers.
异常的蛋白质糖基化在许多类型的疾病进展中都有观察到,包括不同类型的癌症。在这项研究中,我们通过 PGC-ESI-MS/MS 评估了人乳腺癌细胞和组织的差异 N-糖型模式。与乳腺上皮细胞相比,乳腺癌细胞中的高甘露糖聚糖明显升高。然而,组织中 N-聚糖的改变比细胞中更为明显。共稳定鉴定了 63 种不同的 N-聚糖,其中 38 种在癌旁组织和乳腺癌组织之间存在显著差异。在乳腺癌组织中,高甘露糖聚糖和核心岩藻糖基化聚糖增加,而双分支聚糖和唾液酸化聚糖减少。此外,良性乳腺肿瘤和乳腺癌组织之间共有 27 种 N-聚糖存在明显差异,其中大多数包括双分支和唾液酸化聚糖在癌症组织中的相对丰度降低。总的来说,三种高甘露糖 N-聚糖(F0H6N2S0、F0H7N2S0、F0H8N2S0)在乳腺癌细胞和组织中均表现出显著的诊断准确性,表明它们在生物标志物中具有潜在作用。此外,还发现唾液酸化聚糖与患者年龄之间存在负相关。总之,我们的研究结果可能有助于了解 N-聚糖在乳腺癌进展中的作用,并提出潜在的诊断生物标志物。