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乳腺癌患者血清神经节苷脂谱分析:GM3 作为一种潜在的诊断生物标志物。

Gangliosides profiling in serum of breast cancer patient: GM3 as a potential diagnostic biomarker.

机构信息

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.

Qingdao Municipal Hospital, The Affiliated Qingdao Municipal Hospital, Qingdao University Medical College, Qingdao, 266071, China.

出版信息

Glycoconj J. 2019 Oct;36(5):419-428. doi: 10.1007/s10719-019-09885-z. Epub 2019 Jul 11.

Abstract

Gangliosides altered during the pathological conditions and particularly in cancers. Here, we aimed to profile the gangliosides in breast cancer serum and propose potential biomarkers. LC-FTMS method was first used to identify all the ganglioside species in serum, then LC-MS/MS-MRM method was employed to quantitate the levels of gangliosides in serum from healthy volunteers and patients with benign breast tumor or breast cancer. 49 ganglioside species were determined, including GM1, GM2, GM3, GD1, GD3 and GT1 species. Compared to healthy volunteers, the levels of GM1, GM2, GM3, GD1 and GD3 displayed a rising trend in breast cancer patients. In particular, as the major glycosphingolipid component, GM3 showed excellent diagnostic accuracy in cancer serum (AUC > 0.9). PCA profile of the GM3 species showed clear distinction between normal and cancer serum. What's more, ROC curve proved great diagnostic accuracy of GM3 between cancer and benign serum. In addition, GM3 was discovered as a diagnostic marker to differentiate luminal B subtype from other subtypes. Furthermore, a positive correlation between GM3 and Ki-67 status of patients was identified. In conclusion, our results introduced the alteration patterns of serum gangliosides in breast cancer and suggested serum GM3 as a potential diagnostic biomarker in breast cancer diagnosis and luminal B subtype distinction.

摘要

神经节苷脂在病理条件下发生改变,尤其是在癌症中。在这里,我们旨在分析乳腺癌血清中的神经节苷脂谱,并提出潜在的生物标志物。首先使用 LC-FTMS 方法鉴定血清中的所有神经节苷脂种类,然后使用 LC-MS/MS-MRM 方法定量测定健康志愿者、良性乳腺肿瘤患者和乳腺癌患者血清中的神经节苷脂水平。确定了 49 种神经节苷脂种类,包括 GM1、GM2、GM3、GD1、GD3 和 GT1 种类。与健康志愿者相比,GM1、GM2、GM3、GD1 和 GD3 的水平在乳腺癌患者中呈上升趋势。特别是 GM3 作为主要的糖脂成分,在癌症血清中具有出色的诊断准确性(AUC > 0.9)。GM3 种类的 PCA 图谱显示正常和癌症血清之间有明显区别。此外,ROC 曲线证明 GM3 在癌症和良性血清之间具有很好的诊断准确性。此外,GM3 被发现是区分腔 B 亚型与其他亚型的诊断标志物。此外,还确定了 GM3 与患者 Ki-67 状态之间的正相关关系。总之,我们的结果介绍了乳腺癌血清中神经节苷脂的改变模式,并提出血清 GM3 作为乳腺癌诊断和区分腔 B 亚型的潜在诊断生物标志物。

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