Accurate determination for lipidomics based on LC-tandem-MS parameters modeling, prediction, and database: Monitoring the progression of hepatocellular carcinoma

The unavailability of adequate lipid reference standards is a major challenge for accurate quantitative analysis of lipidomics. Based on the discovery of regularity and predictability for lipids in chromatography-mass spec-trometry behaviors, target compound-structure correlation-analytical parameter database protocol and modeling-prediction strategy were carried out to calculate the relative coefficients of analytical parameters within each subclass. Then the relevant LC-tandem-MS parameters of unknown lipids were predicted and a quantification parameter database for 4081 lipids was established and validated. Reference standards -independent accurate determination for lipidomics was achieved with the parameter's database and applied to monitor the change of lipid metabolism in the plasma of whole course of health-hepatitis-cirrhosis-hepatocellular carcinoma (HCC). Combined Student's t test, orthogonal partial least squares discrimination analysis (OPLS-DA) and binary logistic regression-ROC analysis, lipid biomarkers for differentiating health from each disease and differentiating different stages of disease were identified and the pathogenesis of HCC was preliminarily clarified. The established methodology would shed light on comprehensive and accurate quanti-tative lipidomics and exploring the pathomechanism and potential therapeutic targets of HCC.

Automated summary

The lack of adequate lipid reference standards is a major challenge for accurate quantitative analysis in lipidomics. Through the discovery of regularity and predictability in chromatography-mass spectrometry behaviors of lipids, a protocol and strategy were developed to calculate correlations between compound structures and analytical parameters within each lipid subclass. This allowed for the prediction of relevant LC-tandem-MS parameters for unknown lipids, and the establishment and validation of a quantification parameter database for 4081 lipids. This methodology was applied to monitor lipid metabolism changes in the plasma of health-hepatitis-cirrhosis-hepatocellular carcinoma (HCC) progression, and resulted in the identification of lipid biomarkers for distinguishing between health and different diseases, as well as different stages of disease.