School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, Georgia 30332, United States.
Petit Institute of Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia 30332, United States.
J Proteome Res. 2023 Jun 2;22(6):2092-2108. doi: 10.1021/acs.jproteome.3c00226. Epub 2023 May 23.
Ovarian cancer (OC) is one of the deadliest cancers affecting the female reproductive system. It may present little or no symptoms at the early stages and typically unspecific symptoms at later stages. High-grade serous ovarian cancer (HGSC) is the subtype responsible for most ovarian cancer deaths. However, very little is known about the metabolic course of this disease, particularly in its early stages. In this longitudinal study, we examined the temporal course of serum lipidome changes using a robust HGSC mouse model and machine learning data analysis. Early progression of HGSC was marked by increased levels of phosphatidylcholines and phosphatidylethanolamines. In contrast, later stages featured more diverse lipid alterations, including fatty acids and their derivatives, triglycerides, ceramides, hexosylceramides, sphingomyelins, lysophosphatidylcholines, and phosphatidylinositols. These alterations underscored unique perturbations in cell membrane stability, proliferation, and survival during cancer development and progression, offering potential targets for early detection and prognosis of human ovarian cancer.
卵巢癌（OC）是影响女性生殖系统的最致命癌症之一。它在早期可能几乎没有症状，而在晚期则通常没有特异性症状。高级别浆液性卵巢癌（HGSC）是导致大多数卵巢癌死亡的亚型。然而，人们对这种疾病的代谢过程知之甚少，特别是在早期阶段。在这项纵向研究中，我们使用稳健的 HGSC 小鼠模型和机器学习数据分析来研究血清脂质组变化的时间过程。HGSC 的早期进展以磷脂酰胆碱和磷脂酰乙醇胺水平升高为标志。相比之下，后期则表现出更多样化的脂质变化，包括脂肪酸及其衍生物、甘油三酯、神经酰胺、己糖神经酰胺、鞘磷脂、溶血磷脂酰胆碱和磷脂酰肌醇。这些变化突出了在癌症发生和发展过程中细胞膜稳定性、增殖和存活的独特干扰，为人类卵巢癌的早期检测和预后提供了潜在的靶点。
