Citation: Jialin Liu, Qingce Zang, Xinzhu Li, Xinyi Tu, Ying Zhu, Lingzhi Wang, Zitong Zhao, Yongmei Song, Ruiping Zhang, Zeper Abliz. On-tissue chemical derivatization enables spatiotemporal heterogeneity visualization of oxylipins in esophageal cancer xenograft via ambient mass spectrometry imaging[J]. Chinese Chemical Letters, ;2023, 34(11): 108322. doi: 10.1016/j.cclet.2023.108322 shu

On-tissue chemical derivatization enables spatiotemporal heterogeneity visualization of oxylipins in esophageal cancer xenograft via ambient mass spectrometry imaging

Jialin Liu ^a ,
Qingce Zang ^{a, *,} ,
Xinzhu Li ^a ,
Xinyi Tu ^a ,
Ying Zhu ^a ,
Lingzhi Wang ^a ,
Zitong Zhao ^b ,
Yongmei Song ^b ,
Ruiping Zhang ^a ,
Zeper Abliz ^{a, c, d, *,}

a.
State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
b.
State Key Laboratory of Molecular Oncology, Cancer Institute, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
c.
Key Laboratory of Mass Spectrometry Imaging and Metabolomics (Minzu University of China), National Ethnic Affairs Commission, Beijing 100081, China
d.
Center for Imaging and Systems Biology, College of Life and Environmental Sciences, Minzu University of China, Beijing 100081, China

zangqingce@imm.ac.cn

zeper@imm.ac.cn

zeper@muc.edu.cn

Received Date: 4 November 2022
Revised Date: 22 February 2023
Accepted Date: 8 March 2023
Available Online: 11 March 2023

Figures(4)

On-tissue chemical derivatization (OTCD) effectively enhances ionization efficiency of low abundant and poorly ionized functional molecules to improve detection sensitivity and coverage of mass spectrometry imaging (MSI). Combination OTCD and MSI provides a novel strategy for visualizing previously undisclosed metabolic heterogeneity in tumor. Herein, we present a method to visualize heterogeneous metabolism of oxylipins within tumor by coupling OTCD with airflow-assisted desorption electrospray ionization (AFADESI)-MSI. Taking Girard's P as a derivatization reagent, easily ionized hydrazide and quaternary amine groups were introduced into the structure of carbonyl metabolites via condensation reaction. Oxylipins, including 127 fatty aldehydes (FALs) and 71 oxo fatty acids (FAs), were detected and imaged in esophageal cancer xenograft with AFADESI-MSI after OTCD. Then t-distributed stochastic neighbor embedding and random forest were exploited to precisely locate the distribution of oxylipins in heterogeneous tumor tissue. With this method, we surprisingly found almost all FALs and oxo FAs significantly accumulated in the core region of tumor, and exhibited a gradual increase trend in tumor over time. These results reveal spatiotemporal heterogeneity of oxylipins in tumor progression, highlighting the value of OTCD combined with MSI to gain deeper insights into understanding tumor metabolism.
- On-tissue chemical derivatization,
- Ambient mass spectrometry imaging,
- Oxylipins,
- Esophageal cancer,
- Metabolic heterogeneity
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