Machine Learning Reveals Lipidome Remodeling Dynamics in a Mouse Model of Ovarian Cancer

Olatomiwa O. Bifarin & Facundo M. Fernández et al. · 2023-05-23

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.
Funding

NCI NIH HHS

R01 CA218664

NCI NIH HHS

R03 CA259664

National Cancer Institute

1R01CA218664-01

National Cancer Institute

R03CA259664

Cancer Prevention and Research Institute of Texas

RP220524