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Lipidomic study and diagnosis of hepatocellular carcinoma tumor with rapid evaporative ionization mass spectrometry
Authors:Haixing Wang  Ting Li  Qing Shen  Zhifang Liu  You-Wei Chen  Darong Huang  Jiancheng Yu  Long Wang
Institution:1. Zhejiang Provincial Key Laboratory of Anesthesiology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, P. R. China;2. Collaborative Innovation Center of Seafood Deep Processing, Zhejiang Province Joint Key Laboratory of Aquatic Products Processing, Institute of Seafood, Zhejiang Gongshang University, Hangzhou, P. R. China;3. Zhejiang Provincial People's Hospital, Affiliated People's Hospital of Hangzhou Medical College, Hangzhou, P. R. China;4. Hangzhou Linping Hospital of Traditional Chinese Medicine, Hangzhou, P. R. China;5. Zhejiang Engineering Research Center of Advanced Mass Spectrometry and Clinical Application, Faculty of Electrical Engineering and Computer Sciences, Ningbo University, Ningbo, P. R. China;6. Department of Hand and Plastic Surgery, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, P. R. China
Abstract:Liver cancer is generally considered the leading cause of cancer deaths worldwide, and hepatocellular carcinoma (HCC) contributes to more than 90% of liver cancers. The altered lipid metabolism for rapid cancer cell growth and tumor formation has been frequently proven. In this study, an ambient ionization mass spectrometry technique, rapid evaporative ionization mass spectrometry (REIMS) using a monopolar electric knife, called iKnife, was systematically optimized and employed for ex vivo analysis of 12 human HCC tumor tissue specimens together with the paired paracancerous tissue (PT) and noncancerous liver tissue (NCT) specimens. Nine free fatty acids and 34 phospholipids were tentatively identified according to their extract masses and/or tandem mass spectra. With the help of statistical methods, 7 free fatty acids and 10 phospholipids were distributed differently in 3 types of liver tissue specimens (95% confidence interval). The box plots showed these characterized lipid metabolites varied in PT, HCC, and NCT. Compared with PT and NCT, the upregulations of four common fatty acids FA 18:0, FA 20:4, FA 16:0, and FA 18:1, together with phospholipids PC 36:1, PE 38:3, PE (18:0/20:4), PA (O-36:1), PC (32:1), PC 32:0, PE 34:0, and PC (16:0/18:1), were found in HCC specimens. The sensitivity and specificity of the established statistic model for real-time HCC tumor diagnosis were 100% and 90.5%, respectively. This study demonstrated that the described REIMS technique is a potential method for rapid lipidomic analysis and characterization of HCC tumor tissue.
Keywords:fatty acid  hepatocellular carcinoma  lipidomics  phospholipid  rapid evaporative ionization mass spectrometry
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