卵巢癌中血小板和血小板衍生微粒的脂质谱

Qianghua Hu , Miao Wang , Min Soon Cho , Chunyan Wang , Alpa M. Nick , Perumal Thiagarajan , Fleur M. Aung , Xianlin Han , Anil K. Sood , Vahid Afshar-Kharghan
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引用次数: 30

摘要

背景:卵巢癌患者发生静脉血栓的风险很高。血小板和血小板衍生微粒(PMP)的膜脂双分子层为凝血蛋白的组装和血栓的形成提供了平台。方法将卵巢癌患者的血小板脂质组成和pmp与健康人进行比较。我们使用散弹枪脂组学对12类177种脂质进行了量化。结果卵巢癌患者血小板和pmp中2类脂质有显著变化:磷脂酰肌醇升高,溶磷脂酰胆碱降低。28种脂质的水平也发生了显著的变化,呈促凝剂增加和抗凝剂减少的方向。我们发现癌症血小板比正常血小板表达更少的脂质磷酸磷酸酶1 (LPP1),这是磷脂生物合成途径的关键酶。LPP1的减少可能有助于癌症血小板脂质谱的变化。结论:我们的研究结果支持卵巢癌患者血小板促凝脂质谱可能在这些患者静脉血栓形成风险增加中发挥作用。据我们所知,我们的研究是第一个在卵巢癌中应用血小板脂质组学的研究。我们的发现对未来研究的重要性在于:1)血小板和PMP的脂质谱的类似变化可能与其他癌症的高凝性有关;2)静脉血栓形成的血浆高危脂质水平可能是有用的生物标志物。
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Lipid profile of platelets and platelet-derived microparticles in ovarian cancer

Background

Ovarian cancer patients have a high risk of developing venous thrombosis. The membrane lipid bilayer of platelets and platelet-derived microparticles (PMP) provides a platform for assembly of coagulation proteins and generation of blood clots.

Methods

We compared the lipid composition of platelets and PMPs in patients with ovarian cancer to those in healthy subjects. We used shotgun lipidomics to quantify 12 classes and 177 species of lipids.

Results

We found a significant change in 2 classes of lipids in platelets and PMPs isolated from ovarian cancer patients: higher phosphatidylinositol and lower lyso-phosphatidylcholine. The level of 28 species of lipids was also significantly altered in the direction of an increase in the pro-coagulant and a reduction in the anticoagulant lipids. We found that cancer platelets expressed less lipid phosphate phosphatase 1 (LPP1), a key enzyme in phospholipid biosynthesis pathways, than normal platelets. The reduction in LPP1 might contribute to the changes in the lipid profile of cancer platelets.

Conclusion

Our results support a procoagulant lipid profile of platelets in ovarian cancer patients that can play a role in the increased risk of venous thrombosis in these patients.

General significance

As far as we are aware, our study is the first study on platelet lipidomics in ovarian cancer. The importance of our findings for the future studies are: 1) a similar change in lipid profile of platelets and PMP may be responsible for hypercoagulability in other cancers, and 2) plasma level of high-risk lipids for venous thrombosis may be useful biomarkers.

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