Comparative study of alterations in phospholipid profiles upon liver cancer in humans and mice. Issue 20 (28th August 2020) - Lu, Haiyan
Abstract : The relevance of molecular alterations between mouse liver cancer models and humans was studied by iEESI-MS analysis; revealing differences in the alterations of phospholipids between humans and mice and pinpointing similarly behaving phospholipids. Abstract : Comparative studies of molecular alterations upon cancer between mice and humans are of great importance in order to determine the relevance of research involving mouse cancer models to the development of diagnostic and therapeutic approaches in clinical practice as well as for the mechanistic studies of pathology in humans. Herein, using molecular fingerprinting by internal extractive electrospray ionization mass spectrometry (iEESI-MS), we identified 50 differential signals in mouse liver tissue and 62 differential signals in human liver tissue that undergo significant intensity alterations (variable importance in the project (VIP) >1.0) upon liver cancer, out of which only 27 were common in both mouse and human tissues. Out of the 27 common differential signals, six types of phospholipids were also identified to undergo significant alterations in human serum upon liver cancer, including PC(34:2), PC(36:4), PC(38:6), PC(36:2), PC(38:4) and PC(42:9). Statistical analysis of the relative intensity distribution of these six identified phospholipids in serum allowed confident determination of liver cancer in humans (sensitivity 91.0%, specificity 88.0%, and accuracy 90.0%). Our results indicate that, despite the significant difference in the overall alterations of phospholipid profiles upon liver cancer between humans and mice, the six identified 'core' differential phospholipids of liver cancer found in the liver tissues of both humans and mice as well as in human serum show high potential as a minimal panel for the rapid targeted diagnosis of liver cancer with high accuracy, sensitivity and specificity using direct mass spectrometry (MS) analysis.