Lipid profile of platelets and platelet-derived microparticles in ovarian cancer.
Lipid profile of platelets and platelet-derived microparticles in ovarian cancer.
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DOI：
10.1016/j.bbacli.2016.06.003
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发表时间：
2016-12
期刊：
影响因子：
--
通讯作者：
Afshar-Kharghan V
中科院分区：
文献类型：
--
作者：
Hu Q;Wang M;Cho MS;Wang C;Nick AM;Thiagarajan P;Aung FM;Han X;Sood AK;Afshar-Kharghan V
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)的膜脂双层为凝血蛋白的组装和血栓的形成提供了平台。我们比较了卵巢癌患者和健康人的血小板和PMPs的脂质成分。我们使用猎枪脂类组学对12类177种脂类进行了量化。我们发现卵巢癌患者血小板和PMPs中的两类脂类发生了显著变化：较高的磷脂酰肌醇和较低的溶血磷脂酰胆碱。28种脂类的水平也在促凝血剂增加和抗凝剂脂类减少的方向上有显着变化。我们发现，与正常血小板相比，癌症患者血小板表达磷脂生物合成途径的关键酶--脂质磷酸酶1(LPP1)的水平更低。LPP1的降低可能参与了肿瘤血小板脂质谱的变化。我们的结果支持卵巢癌患者血小板的促凝血脂质分布，这可能在这些患者静脉血栓形成的风险增加中发挥作用。据我们所知，我们的研究是第一次关于卵巢癌的血小板脂质组学的研究。我们的研究结果对未来研究的重要性是：1)血小板和PMP的血脂谱相似的变化可能是其他癌症高凝状态的原因，2)静脉血栓形成的高危血脂水平可能是有用的生物标志物。卵巢癌患者血小板和PMP的脂质组成发生改变。血小板和PMP的脂质成分的变化是向促凝方向的。LPP1酶在癌症血小板中被减少。
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. 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. 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. 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. 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. Lipid composition of platelet and PMP is altered in ovarian cancer. The change in lipid composition of platelet and PMP is in a procoagulant direction. LPP1 enzyme is reduced in cancer platelets.