Ether‐Linked Glycerophospholipids Are Potential Chemo‐Desensitisers and Are Associated With Overall Survival in Carcinoma Patients

Lipid reprogramming in carcinoma is reported to have a role in carcinogenesis, prognosis and therapy response. The lipid reprogramming could be contributed by either autonomous or nonautonomous resources. Since the nonautonomous lipid resources contributed by lipoproteins and their receptors have been reported in epithelial ovarian cancer (EOC), the impact of autonomous lipid metabolites was unknown. This report revealed a unique lipid class, ether-linked phosphatidyl-ethanolamine (PE O-), which enhances chemo-insensitivity and progression in EOC and potentially cross carcinomas. Analysis of CCLEC/GDSCC database and in-house cell line lipidomes identified PE O- as the major lipid associated with cisplatin/paclitaxel sensitivity. In the testing of PE O- effect on cancer phenotypes, it enhanced cell growth, migratory activities and promoted cisplatin/paclitaxel insensitivity. In addition, treating AGPS inhibitor-sensitised chemo-cytotoxic upon cisplatin/paclitaxel treatments. Treating PE O- could reverse AGPS inhibitor chemosensitisation effect on EOC cells. At last, using TCGA-EOC transcriptome database, the PE O- related gene expressions were positive correlated with patient prognosis in general, or in whom were treated with platin- or taxel-based chemotherapies. The expressions of genes for the synthesis of PE O- aggravates therapy response in EOC patients. PE O- facilitates human carcinoma cell line growth, mobility and chemo-insensitivity.