Imperial College London
Dr Emrys Jones

DrEmrysJones

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Honorary Research Associate
 
 
 
//

Contact

 

emrys.jones

 
 
//

Location

 

Sir Alexander Fleming BuildingSouth Kensington Campus

//

Summary

 

Publications

Citation

BibTex format

@article{Abbassi-Ghadi:2020:10.1158/0008-5472.CAN-19-4035,
author = {Abbassi-Ghadi, N and Antonowicz, S and McKenzie, J and Kumar, S and Huang, J and Jones, E and Strittmatter, N and Petts, G and Kudo, H and court, S and Hoare, J and Veselkov, K and Goldin, R and Takats, Z and Hanna, G},
doi = {10.1158/0008-5472.CAN-19-4035},
journal = {Cancer Research},
pages = {2764--2774},
title = {De novo lipogenesis alters the phospholipidome of esophageal adenocarcinoma},
url = {http://dx.doi.org/10.1158/0008-5472.CAN-19-4035},
volume = {80},
year = {2020}
}
Download

RIS format (EndNote, RefMan)

TY  - JOUR
AB  - The incidence of esophageal adenocarcinoma is rising, survival remains poor, and new tools to improve early diagnosis and precise treatment are needed. Cancer phospholipidomes quantified with mass spectrometry imaging can support objective diagnosis in minutes using a routine frozen tissue section. However, whether mass spectrometry imaging can objectively identify primary esophageal adenocarcinoma is currently unknown and represents a significant challenge, as this microenvironment is complex with phenotypically similar tissue-types. Here we used desorption electrospray ionisation mass spectrometry imaging (DESI-MSI) and bespoke chemometrics to assess the phospholipidomes of esophageal adenocarcinoma and relevant control tissues. Multivariable models derived from phospholipid profiles of 117 patients were highly discriminant for esophageal adenocarcinoma both in discovery (area-under-curve = 0.97) and validation cohorts (AUC = 1). Among many other changes, esophageal adenocarcinoma samples were markedly enriched for polyunsaturated phosphatidylglycerols with longer acyl chains, with stepwise enrichment in pre-malignant tissues. Expression of fatty acid and glycerophospholipid synthesis genes was significantly upregulated, and characteristics of fatty acid acyls matched glycerophospholipid acyls. Mechanistically, silencing the carbon switch ACLY in esophageal adenocarcinoma cells shortened GPL chains, linking de novo lipogenesis to the phospholipidome. Thus, DESI-MSI can objectively identify invasive esophageal adenocarcinoma from a number of pre-malignant tissues and unveils mechanisms of phospholipidomic reprogramming. These results call for accelerated diagnosis studies using DESI-MSI in the upper gastrointestinal endoscopy suite as well as functional studies to determine how polyunsaturated phosphatidylglycerols contribute to esophageal carcinogenesis.
AU  - Abbassi-Ghadi,N
AU  - Antonowicz,S
AU  - McKenzie,J
AU  - Kumar,S
AU  - Huang,J
AU  - Jones,E
AU  - Strittmatter,N
AU  - Petts,G
AU  - Kudo,H
AU  - court,S
AU  - Hoare,J
AU  - Veselkov,K
AU  - Goldin,R
AU  - Takats,Z
AU  - Hanna,G
DO  - 10.1158/0008-5472.CAN-19-4035
EP  - 2774
PY  - 2020///
SN  - 0008-5472
SP  - 2764
TI  - De novo lipogenesis alters the phospholipidome of esophageal adenocarcinoma
T2  - Cancer Research
UR  - http://dx.doi.org/10.1158/0008-5472.CAN-19-4035
UR  - https://cancerres.aacrjournals.org/content/80/13/2764
UR  - http://hdl.handle.net/10044/1/79476
VL  - 80
ER  -
Download