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

Gangliosides profiling in serum of breast cancer patient: GM3 as a potential diagnostic biomarker
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乳腺癌患者血清中的神经节苷脂分析:GM3 作为潜在的诊断生物标志物

DOI:
10.1007/s10719-019-09885-z
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发表时间:
2019-10-01
影响因子:
3
通讯作者:
Li, Guoyun
Li, Guoyun
中科院分区:
生物学4区
文献类型:
--
作者:
Li, Qinying;Sun, Mei;Li, Guoyun

文献摘要

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神经节苷脂在病理条件下发生变化,特别是在癌症中。在这里,我们的目的是分析乳腺癌血清中的神经节苷脂,并提出潜在的生物标志物。首先采用LC-FTMS法鉴定血清中神经节苷脂的种类,然后采用LC-MS/MS-MRM法测定健康志愿者、乳腺良性肿瘤患者和乳腺癌患者血清中神经节苷脂的含量。测定了49种神经节苷脂,包括GM 1、GM 2、GM 3、GD 1、GD 3和GT 1。与健康志愿者相比,乳腺癌患者血清GM 1、GM 2、GM 3、GD 1和GD 3水平呈上升趋势。特别地,作为主要的鞘糖脂组分,GM 3在癌症血清中显示出优异的诊断准确性(AUC > 0.9)。GM 3种类的PCA谱在正常和癌症血清之间显示出明显的区别。ROC曲线显示GM 3在恶性肿瘤和良性肿瘤血清中的诊断准确性较高。此外,发现GM 3可作为区分管腔型B亚型与其他亚型的诊断标志物。此外,GM 3和Ki-67状态的患者之间的正相关性被确定。总之,我们的研究结果介绍了血清神经节苷脂在乳腺癌中的变化模式,并建议血清GM 3作为乳腺癌诊断和管腔B亚型区分的潜在诊断生物标志物。
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.