| Objective: This study was conducted on the basis of ultra-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS)technology platform,the serum lipid metabolic profiles of patients with esophageal squamous cell carcinoma(ESCC)and reflux esophagitis(RE),and healthy control(HC)population were examined and analyzed using non-targeted lipidomics.The aim of the study is to explore the possible differential lipid molecules,and to provide new clinical insights into the diagnosis and treatment of ESCC from the perspective of lipid metabolism.Methods: Between March 2021 and May 2022,serum samples from 44 patients with ESCC,24 patients with RE patients,and 42 sex-age-matched healthy control individuals were collected at the First Affiliated Hospital of Wannan Medical College for lipidomic analysis,a combination of multivariate and univariate statistical analysis was applied to screen and identify potential lipid biomarkers;the relationships between differentially expressed lipids and their possible influencing lipid metabolic pathways were described using correlation and metabolic pathway enrichment analysis;finally,the receiver operating characteristic(ROC)curves were conducted to evaluate the diagnostic performance of candidate lipid biomarkers,and binary logistic regression was also performed to select the best combination of lipid biomarkers.Results: 1.In this study,a total of 140 lipid species were detected in positive and negative ion modes from 110 serum samples by UPLC-Q-TOF-MS.2.A total of 12 lipid species were significantly differentially expressed between ESCC and HC groups,of which 9 differential lipids were down-regulated and 3 was up-regulated in ESCC,including 6 glycerophospholipids,1 sphingolipid,1 triglyceride and 4 fatty acids.ROC curve analysis showed that the AUC values of Arachidonic acid,PS(22:4/19:0),PS(18:3/19:0)and PS(15:1/20:0)were greater than 0.8,indicating that these lipid species have excellent discriminatory ability and could be used as potential lipid biomarkers for diagnosis of ESCC.Besides,the analysis of KEGG metabolic pathway revealed that differential lipid species were mainly involved in the metabolism of glycerophospholipids in ESCC.3.A total of 10 differential lipid species were screened between RE and HC groups,the expression of PE(22:6/19:0),SM(d18:2/16:0),and PC(22:6/13:0)was upregulated in RE group compared with HC,and the other 7 species were down-regulated in RE patients.ROC curve analysis showed that the AUC values of PI(20:4/16:0),PE(P-16:0/22:6),PS(21:0/16:0)and PE(O-16:0/18:3)were 0.841,0.819,0.809 and 0.805,respectively,indicating that these differential lipid molecules could well distinguish RE patients from healthy controls.4.The 10 differential lipid molecules between ESCC and RE groups included(R)-2-Hydroxyhexadecanoic acid,PS(18:4/21:0),PS(15:1/20:0),Arachidonic acid,12 E,16E-octadecadienoic acid,PS(18:1/22:0),TG(14:1/14:1/22:6),PS(22:4/19:0),11S-Hydroxyhexadecanoic acid and PS(18:3/19:0),and all 10 differential lipids were upregulated in ESCC group compared to RE patients.ROC curve analysis showed that the AUC values of(R)-2-Hydroxyhexadecanoic acid,PS(18:4/21:0)and PS(15:1/20:0)were 0.879,0.865 and 0.847,respectively,indicating that these lipids are potentially of clinical diagnostic value due to their high sensitivity in discriminating ESCC patients from benign controls(RE patients).5.The common three differential lipids between ESCC and HC groups,RE and HC groups and ESCC and RE groups were12 E,16E-octadecadienoic acid,Arachidonic acid and TG(14:1/14:1/22:6),ROC curve analysis showed that the AUC values of the combined diagnostic model were 0.905,0.773 and 0.803,respectively,indicating that the diagnostic model could well differentiate between ESCC,RE and HC groups,and can be used as a potential combination of diagnostic lipid biomarkers.Conclusion: Disturbances in lipid metabolism are evident in the serum of patients with esophageal squamous cell carcinoma and reflux esophagitis,and glycerophospholipid metabolism may be more disturbed in patients with ESCC.The differential lipids could well distinguish ESCC,RE and healthy controls,and differential lipids with high AUC values(> 0.8)between the groups could be considered as potential lipid biomarkers for disease diagnosis.This study provides a scientific basis for exploring the pathogenesis of esophageal cancer at the level of lipid metabolism and may help to provide new directions and ideas for clinical diagnosis of ESCC. |
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