Chemically Induced Brain Cancer in Sprague-Dawley Rats: Changed Lipidomics Mimics the Human Conditions

A. Leskanicova, P. Simko, M. Babinčák, A. Blicharova, M. Kertys, J. Kostolný, D. Maceková, T. Kiskova
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Abstract

Malignant gliomas are one of the most treatment-refractory cancers. Development of resistance to chemo- and radiotherapies contributes to these tumors’ aggressive phenotypes. Elevated lipid levels in gliomas have been reported for the last 50 years. However, the molecular mechanisms of how tumor tissues obtain lipids and utilize them are not well understood.In our study, 48.6% of phosphatidylcholines were significantly changed during an early stage of brain cancer in females, and 66.2% in males. As for lysophosphatidylcholines 57.1% metabolites were significantly changed in female, and 64.3% in male rats. We observed the most interesting results in the group of sphingomyelins, where 85.8% metabolites were significantly elevated during brain cancer. According to VIP projection, the most important metabolites were: PC ae C40:3, PC ae C38:1, PC ae C30:1, PC ae C38:3, PC ae C44:3, PC aa C40:2, PC aa C42:0, PC ae C30:2, SM C20:2, PC aa C42:1 in females, and PC ae C38:1, PC ae C40:3, PC ae C30:1, PC ae C42:1, SM C20:2, PC aa C34:4, PC ae C38:4, PC aa C32:2, PC aa C38:5, lysoPC a C14:0. The identification of lipid biomarkers during the early stage of cancer could improve patient prognosis.
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化学诱导的 Sprague-Dawley 大鼠脑癌:改变后的脂质组学模拟人类状况
恶性胶质瘤是最难治疗的癌症之一。对化疗和放疗产生抗药性是这些肿瘤具有侵袭性表型的原因之一。过去 50 年来,胶质瘤中脂质水平升高的报道屡见不鲜。在我们的研究中,48.6%的磷脂酰胆碱在女性脑癌早期发生了显著变化,而在男性中则为 66.2%。至于溶血磷脂酰胆碱,57.1%的代谢物在雌性大鼠和 64.3%的雄性大鼠中发生了明显变化。我们在鞘磷脂组观察到了最有趣的结果,其中 85.8%的代谢物在脑癌期间明显升高。根据 VIP 预测,最重要的代谢物是PC ae C40:3、PC ae C38:1、PC ae C30:1、PC ae C38:3、PC ae C44:3、PC aa C40:2、PC aa C42:0、PC ae C30:2、SM C20:2、PC aa C42:雌性为 PC ae C38:1、PC ae C40:3、PC ae C30:1、PC ae C42:1、SM C20:2、PC aa C34:4、PC ae C38:4、PC aa C32:2、PC aa C38:5、溶菌酶PC a C14:0。在癌症早期识别脂质生物标志物可改善患者的预后。
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