1 SCIENTIFIC REPORTS | 7: 3858 | DOI:10.1038/s41598-017-04202-w www.nature.com/scientificreports LC-MS/MS quantification of sulfotransferases is better than conventional immunogenic methods in determining human liver SULT activities: implication in precision medicine Cong Xie 1,2 , Tong-meng Yan 2,5 , Jia-mei Chen 2 , Xiao-yan Li 2 , Juan Zou 2 , Li-jun Zhu 2 , Lin-lin Lu 2 , Ying Wang 2 , Fu-yuan Zhou 2,3 , Zhong-qiu Liu 1,2 & Ming Hu 4 This study aims to determine whether enzyme activities are correlated with protein amounts and mRNA expression levels of five major human sulfotransferase (SULT) enzymes in 10 matched pericarcinomatous and hepatocellular carcinoma liver samples. The MRM UHPLC-MS/MS method, Western blot and RT-PCR were used along with SULT activity measurement using probe substrates. The LC-MS/MS method was specific for all five tested SULTs, whereas Western blot was specific for only two isoforms. The activities of SULT1A1, SULT1B1, SULT1E1 and SULT2A1 in 9 of 10 samples showed a significant decrease in tumor tissues relative to matched pericarcinomatous tissues, whereas the activities of SULT1A3 in 7 of 10 samples increased. The turnover numbers of SULTs did not change, except for SULT1A1. A generally high degree of correlations was observed between SULT activities and protein amounts (r 2 ≥ 0.59 except one), whereas a low degree of correlations was observed between SULT activities and mRNA expression levels (r 2 ≤ 0.48 except one). HCC reduced the SULT activities via impaired protein amounts. LC-MS/MS quantification of SULTs is highly reliable measurement of SULT activities, and may be adopted for implementing precision medicine with respect to drugs mainly metabolized by SULTs in healthy and HCC patients. Precision medicine is a broad and rapidly advancing field in health care that considers the unique clinical, genetic, and environmental information of individuals 1 . Precision medicine was first practiced in oncology because of its potential to enhance targeted cancer therapies 2 . Precision medicine focuses on the following four significant aspects: human genetic information, transcription, protein and function/activity 3, 4 . Although defining genetic information and its transcription is quite common and easy, proteins and their activities should be determined to understand their biological in case of changes in their functions 5 . e latter may also enhance our understanding of the molecular pathogenesis of a disease 6 . Hence, proteins and their activities have the potential to serve as biomarkers associated with disease diagnosis, prognosis, stratification, and treatment 7 . Unfortunately, because 1 Department of Pharmaceutics, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong, 510515, China. 2 International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006, China. 3 Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, China. 4 Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX, 77030, USA. 5 State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau (SAR), China. Cong Xie and Tong-meng Yan contributed equally to this work. Correspondence and requests for materials should be addressed to F.-y.Z. (email: fuyuan@fimmu.com) or Z.-q.L. (email: liuzq@gzucm.edu.cn) or M.H. (email: mhu@uh.edu) Received: 6 February 2017 Accepted: 10 May 2017 Published: xx xx xxxx OPEN