A convenient and efficient 4-(diethylamino)-butylamine-lab ele d polarity-response-homodispersed strategy for absolute quantification of carboxyl submetabolome: Monitoring the whole progressive course of hepatocellular carcinoma

Recent studies have shown that dysregulation of carboxyl submetabolome homeostasis is closely related to the occurrence and development of hepatocellular carcinoma (HCC). However, it is still a challenge to quantify carboxyl metabolites with high efficiency by conventional methods due to their species diver-sity and nature differences. Moreover, there are few studies on carboxyl submetabolome profiling during the whole progression of HCC. In this study, a convenient and efficient workflow for absolute quantifi-cation of carboxyl submetabolome was established based on the 4-(diethylamino)-butylamine (DEABA)-labeled polarity-response-homodispersed strategy. After optimizing derivation conditions with response surface methodology (RSM), the reaction only needed 1 min at room temperature, which radically sim-plified the labeling process. Compared with nonderivatization, the gaps of polarities and responses of the analytes were narrowed by DEABA labeling, realizing the polarity-response-homodispersion. Then reso-lution and sensitivity in HPLC-MS/MS were improved significantly. Ultimately, the workflow was applied to monitor carboxyl metabolic profile in human plasma of the whole progressive course of hepatocellular carcinoma. Combined with analysis of variance (ANOVA), orthogonal partial least squares discrimination analysis (OPLS-DA), Bayesian linear discriminant analysis (BLDA) and other data mining methods, the biomarkers of health-hepatitis-cirrhosis-HCC were screened out, and the diagnostic model was estab-lished. Furthermore, the relevancy between carboxyl submetabolome disorders and the pathogenesis of HCC was investigated. The developed method has the characteristics of high sensitivity, high coverage and high practicability, which is suitable for the study of biomarkers of carboxyl submetabolome in the whole progression of HCC. (c) 2022 Published by Elsevier B.V.

Automated summary

Recent studies have shown that dysregulation of carboxyl submetabolome homeostasis is closely related to the occurrence and development of hepatocellular carcinoma (HCC). This study established a convenient and efficient workflow for absolute quantification of carboxyl submetabolome, which was applied to monitor carboxyl metabolic profile in human plasma of the whole progressive course of HCC. Biomarkers of health-hepatitis-cirrhosis-HCC were screened out and a diagnostic model was established. The relevancy between carboxyl submetabolome disorders and the pathogenesis of HCC was also investigated.