A novel UHPLC-HRMS method for simultaneous determination of 20 amino metabolites and proteins in lymphoma patients' cells and serum.

Journal: Scientific reports
Published Date:

Abstract

Highly sensitive and selective monitoring of amino metabolites such as glutamine, arginine, tryptophan and related proteins played significant roles in early diagnosis and warning of lymphoma. But those limited abundance and lacked chromophore group in vivo were bottleneck of multivariate analysis. This work aims to develop a novel UHPLC-Triple-TOF-HRMS method for simultaneous quantitation of 20 kinds of amino metabolites and tracing different proteins based on a new mass spectrometry probe (3-bromopropyl) triphenylphosphonium (3-BMP) with ability of enhance ionization efficiency and targeted labeling amino functional groups. An excellent linearity with R ≥ 0.9995 and inter- and intra-day RSD were 1.43-5.22% and 1.22-5.87%, respectively. Satisfactory recoveries were 87.09-95.82%. Limit of detection (S/N = 3) was 4.0-12.0 fmol. Further, up-regulated haptoglobin, coagulation factor VII and catalase could directly negatively regulate Ala, Lys and Phe, which caused Trp, His, Ser, Asp and Pro expression decreased significantly in lymphoma patients (p < 0.05). Ultimately, a machine learning model was established to predict lymphoma with accuracy rate of 93.68%. Above all, this study would provide multivariate analysis strategy for in-depth explore relationship aminos associated proteins and pathogenesis and helpful for early warning of lymphoma patients under free-disease state.

Authors

  • Mei Zhang
    Clinical and Research Center for Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Beijing, China.
  • Qingkun Ma
    School of Pharmaceutical Sciences & Institute of Materia Medica, Shandong First Medical University & Shandong Academy of Medical Sciences, National Key Laboratory of Advanced Drug Delivery System, Key Laboratory for Biotechnology Drugs of National Health Commission (Shandong Academy of Medical Sciences), Key Lab for Rare & Uncommon Diseases of Shandong Province, Jinan, 250117, Shandong, China.
  • Han Zhao
  • Ge Sun
    College of Life Science and Bioengineering, Beijing University of Technology, Intelligent Physiological Measurement and Clinical Translation, Beijing International Base for Scientific and Technological Cooperation, Beijing, 100024, China.
  • Tenghua Zhao
    School of Pharmaceutical Sciences & Institute of Materia Medica, Shandong First Medical University & Shandong Academy of Medical Sciences, National Key Laboratory of Advanced Drug Delivery System, Key Laboratory for Biotechnology Drugs of National Health Commission (Shandong Academy of Medical Sciences), Key Lab for Rare & Uncommon Diseases of Shandong Province, Jinan, 250117, Shandong, China.
  • Yuqing Wang
    College of Marine Technology and Environment, Dalian Ocean University, Dalian, Liaoning Province, China.
  • Shiji Chen
    School of Pharmaceutical Sciences & Institute of Materia Medica, Shandong First Medical University & Shandong Academy of Medical Sciences, National Key Laboratory of Advanced Drug Delivery System, Key Laboratory for Biotechnology Drugs of National Health Commission (Shandong Academy of Medical Sciences), Key Lab for Rare & Uncommon Diseases of Shandong Province, Jinan, 250117, Shandong, China.
  • Lele Jia
    School of Pharmaceutical Sciences & Institute of Materia Medica, Shandong First Medical University & Shandong Academy of Medical Sciences, National Key Laboratory of Advanced Drug Delivery System, Key Laboratory for Biotechnology Drugs of National Health Commission (Shandong Academy of Medical Sciences), Key Lab for Rare & Uncommon Diseases of Shandong Province, Jinan, 250117, Shandong, China.
  • Yixiang Song
    School of Life Sciences, Tianjin Polytechnic University, 399 Binshui West Street, Xiqing District, Tianjin, 300387, P.R.China.
  • Yanling Mu
    School of Pharmaceutical Sciences & Institute of Materia Medica, Shandong First Medical University & Shandong Academy of Medical Sciences, National Key Laboratory of Advanced Drug Delivery System, Key Laboratory for Biotechnology Drugs of National Health Commission (Shandong Academy of Medical Sciences), Key Lab for Rare & Uncommon Diseases of Shandong Province, Jinan, 250117, Shandong, China. muyanling@sdfmu.edu.cn.