| Laryngeal cancer is a common malignant tumor in the head and neck,while there are limited biomarkers available for its early diagnosis.Cancer cells in the tumor microenvironment,as well as other types of cells,use a variety of ways to obtain lipids for metabolic reprogramming,which is key to supporting cancer progression and developing cancer characteristics.Lipids drive laryngeal cancer progression through membrane composition,energy replenishment,and signaling during the process of metabolic reprogramming.Lipidomics is a powerful tool to elucidate metabolic network changes in health and disease and mine biomarkers for early diagnosis.In order to screen potential biomarkers and reveal the changes in the lipid metabolism profile of laryngeal cancer,in this study,serum samples from patients with laryngeal cancer,patients with benign laryngeal tumors and healthy volunteers were studied using the lipidomics method based on UHPLC-QTOF-MS.The detailed research results were as follows:(1)A novel method was established for the comprehensive analysis of non-targeted lipid compounds in serum with wide coverage,excellent separation and high accuracy.To develop this lipid analysis method,12 kinds of standard lipids with different classes and structural characteristics were used as probes to optimize chromatographic separation and validate the method.The established analytical method meets the standard requirements of biological experiments,with good linearity(r>0.99)demonstrated by the standard curves,detection limits ranging from 0.5-100 ng/mL,and quantitation limits of 1-200 ng/mL.The intra-day and inter-day precision showed a relative standard deviation and relative error of less than 9.3%and 19.3%,and less than 10%and 18.2%,respectively.The recovery rate ranged from 87.0%-119.3%.(2)A total of 10 potential serum biomarkers of laryngeal cancer were screened,and the key differential lipids sphingolipid 42:2(SM 42:2)and sphingolipid 42:3(SM 42:3)were suggested as potential indicators for monitoring cancer progression.A total of 57 significantly different lipids satisfying VIP>1 and P<0.05 were screened out from the serum of healthy volunteers,patients with laryngeal cancer and patients with benign laryngeal tumors using the non-targeted lipidomics study of UHPLC-QTOFMS.The changes in the lipid metabolism network mainly occurred in phosphatidylcholine(PC),lysophosphatidylcholine(LPC),and sphingolipids(SM)metabolic pathways.Ten significantly different lipids were found to be potential biomarkers for early diagnosis of laryngeal cancer by comparing the healthy group with the disease group.Among them,the concentrations of sphingolipid 42:2(SM 42:2)and sphingolipid 42:3(SM 42:3)showed significant differences among the three groups.The results of bivariate correlation analysis showed that the contents of SM 42:2 and SM 42:3 were correlated with the degree of cancer development,suggesting that both of them can be used as indicators for monitoring the progression of cancer.In conclusion,a method for non-targeted lipid analysis in serum was established by using 12 lipid standards as probes.The method demonstrated wide coverage,excellent separation,and high accuracy.The results of this study revealed that lipid metabolism changes in laryngeal cancer primarily focused on PC,LPC,and SM metabolism.Ten potential serum biomarkers for laryngeal cancer were identified,including the key differential lipids SM 42:2 and SM 42:3,which were suggested as potential indicators for monitoring cancer progression.The regulatory and changes of the lipid metabolism network in laryngeal cancer were elucidated from a lipidomics perspective,and key lipids of metabolism remodeling in laryngeal cancer were explored.This study provides new possibilities for screening laryngeal cancer biomarkers. |
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