Oesophageal adenocarcinoma (OAC) has an unmet clinical need, with five year survival in the
UK remaining at 15%. There has been little improvement with advances in surgical practice or
systemic chemotherapeutic regimens. Early diagnosis holds the key to radical treatment, the
clinical utility of breath testing has highlighted aldehydes as a potential early marker of cancer.
The emerging field of lipidomics has identified variations in lipid composition between cancer
and benign tissue. These observed changes have highlighted phospholipids as particularly
important class responsible for structural membrane stability, cell signalling and replication.
In this research, multiple mass spectrometry techniques were implemented to identify and
correlate lipid abundance with increased aldehyde quantitation. Desorption Electrospray
Ionisation- Mass Spectrometry (DESI-MS) was utilised for lipid profiling in oesophageal
adenocarcinoma tissue to reveal a prevalence of Phosphatidic acids (PA) and
Phosphatidylglycerol (PG) species. Comprehensive bioinformatics analysis highlighted the PG
pathway with significantly dysregulation and positive phenotype to PG production.
The investigation of aldehydes was performed in vivo by lipid oxidation and corroborated in
OAC tissue by a targeted Liquid Chromatography mass spectrometry (LC-MS) method. This
identified medium and long chain aldehydes (Pentanal, Nonanal, Un-decanal) at particularly
increased concentration. To investigate the lipid product correlation, the chemistry of lipid
oxidation was defined and characterised.
To explored the origin of the increased PA and PG a targeted LC-MS method was created and
patient tissue and surface mucus samples were collected at paired sites. The analysis confirmed
a relative increase of PAs and PGs in OAC tissue and mucus of representative intensities
suggesting a correlation between mucus sampling and cell phospholipid concentration.
These data highlight the Phospholipid products of a genetically dysregulated pathway in OAC,
which may contribute to the production of unstable polyunsaturated lipids which are prone to
oxidation and formation of aldehydes.