Serum liquid metabolites reveals the heterogeneity in advanced lung adenocarcinoma patients with EGFR sensitizing mutations.

e21065 Background: There is a differential therapeutic efficacy of advanced lung adenocarcinoma (LUAD) patients with EGFR sensitizing mutations (mEGFR). This study aimed to explore the differences in serum liquid metabolites of EGFR mutation types and to provide further evidence for revealing the mechanism of the difference in efficacy. Methods: In total, 42 LUAD patients with mEGFR (19 deletions or 21 L858R mutations) who received EGFR-TKIs therapy were included. Prospectively collected serum samples before initial treatment were utilized to perform nontargeted liquid metabolomics profiling analyses under the application of Ultrahigh Performance Liquid Chromatography-Mass Spectrometry/Mass Spectrometry (UPLC-MS/MS). Multi-dimensional statistical methods such as partial least squares discrimination analysis (PLS-DA) were used to further screen and identify differential metabolites associated with EGFR mutation type. Results: The metabolic signature molecules in the metabolic profile were extracted, and a total of 1995 positive ion mode (ESI+) and 365 negative ion mode (ESI-) signature molecules were obtained. 29 metabolites displayed significant differences between the two groups, which belong to lipids including phosphatidylcholines (PCs), phosphatidylglycerol (PGs), phosphatidylethanolamine (PEs), ceramides (Cers) and sphingomyelins (SMs). Gene mutation subtypes change the proportion of saturated phospholipids and unsaturated phospholipids, with significantly higher saturated phospholipids in patients with the EGFR 21 L858R mutation. Then, pathway enrichment analysis was performed on the differential metabolites, mainly enriched in glycerophospholipid and sphingolipids metabolism pathway. Conclusions: This study not only demonstrates the heterogeneity of lipid metabolism among gene mutation subtypes, but also provides the possibility to reveal the mechanism of survival differences.