Imperial College London

Emeritus ProfessorJeremyNicholson

Faculty of MedicineDepartment of Metabolism, Digestion and Reproduction

Emeritus Professor of Biological Chemistry
 
 
 
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Contact

 

+44 (0)20 7594 3195j.nicholson Website

 
 
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Assistant

 

Ms Wendy Torto +44 (0)20 7594 3225

 
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Location

 

Office no. 665Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@inproceedings{Mirnezami:2016:10.1200/JCO.2016.34.15_suppl.e15104,
author = {Mirnezami, R and Veselkov, K and Strittmatter, N and Goldin, RD and Kinross, JM and Stebbing, J and Holmes, E and Darzi, AW and Nicholson, JK and Takats, Z},
doi = {10.1200/JCO.2016.34.15_suppl.e15104},
publisher = {American Society of Clinical Oncology},
title = {Spatially resolved profiling of colorectal cancer lipid biochemistry via DESI imaging mass spectrometry to reveal morphology-dependent alterations in fatty acid metabolism},
url = {http://dx.doi.org/10.1200/JCO.2016.34.15_suppl.e15104},
year = {2016}
}

RIS format (EndNote, RefMan)

TY  - CPAPER
AB - Background: Lipid metabolic alterations are recognised as potential oncogenic triggers that promote malignant transformation. Here we performed spatially-resolved profiling of lipid signatures in colorectal cancer (CRC) tissue and matched healthy mucosa using desorption electrospray ionisation imaging mass spectrometry (DESI-MSI). The objectives of this study were to comprehensively define the CRC ‘lipidome’ and to assess lipid signatures in discrete histological regions-of-interest, specifically morphologically bland peri-tumoural epithelium (PT-e) and tumour stroma (T-s). Methods: Fresh frozen tissue sections from 42 patients with confirmed CRC were subjected to negative-ion mode DESI-MSI analysis. Mass spectra in the 200-1000 m/zrange were collated from CRC epithelium (CRC-e), PT-e, T-s and healthy tumour-remote epithelium (TR-e). Spectral signatures were subjected to multivariate analysis using a recursive maximum margin criterion (RMMC) algorithm operating in MATLAB. Results: Increased levels of long/very-long chain fatty acids (LCFA/VLCFA) were seen in CRC-e compared with TR-e(AUC = 0.99). Correspondingly, increased expression of lipogenic and elongase enzymes was found on IHC. Transmission electron microscopy was performed to evaluate peroxisomal distribution and morphology in CRC-e, as these organelles metabolise LCFA/VLCFA through β-oxidation, to negligibly low levels, in healthy cells. No discernible difference in peroxisomal distribution, abundance or structure was found between CRC-e and TR-e. PT-e demonstrated a lipid expression pattern almost identical to that of CRC-e, and markedly different from TR-e (AUC = 0.89). Conclusions: A shift towards increased LCFA/VLCFA production may be an important metabolic trait in CRC facilitated through upregulation of de novo lipogenesis and fatty acid elongation and concurrent impairment of peroxisomal β-oxidation. This phenotype was also observed in morphologically bland PT-e, suggesting that
AU - Mirnezami,R
AU - Veselkov,K
AU - Strittmatter,N
AU - Goldin,RD
AU - Kinross,JM
AU - Stebbing,J
AU - Holmes,E
AU - Darzi,AW
AU - Nicholson,JK
AU - Takats,Z
DO - 10.1200/JCO.2016.34.15_suppl.e15104
PB - American Society of Clinical Oncology
PY - 2016///
SN - 0732-183X
TI - Spatially resolved profiling of colorectal cancer lipid biochemistry via DESI imaging mass spectrometry to reveal morphology-dependent alterations in fatty acid metabolism
UR - http://dx.doi.org/10.1200/JCO.2016.34.15_suppl.e15104
UR - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000404665405180&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR - http://hdl.handle.net/10044/1/64022
ER -