Abstract
In this era of precision medicine, there is an increasingly urgent need for highly sensitive tests for detecting tumors such as colon cancer (CC), a silent disease where the first symptoms may take 10–15 years to appear. Mass spectrometry-based lipidomics is an emerging tool for such clinical diagnosis. We used ultra-performance liquid chromatography coupled to electrospray ionization quadrupole time-of-flight mass spectrometry operating in high energy collision spectral acquisition mode (MSE) mode (UPLC-QTOF-MSE) and gas chromatography (GC) to investigate differences between the plasmatic lipidic composition of CC patients and control (CTR) subjects. Key enzymes in lipidic metabolism were investigated using immuno-based detection assays. Our partial least squares discriminant analysis (PLS-DA) resulted in a suitable discrimination between CTR and CC plasma samples. Forty-two statistically significant discriminating lipids were putatively identified. Ether lipids showed a prominent presence and accordingly, a decrease in glyceronephosphate O-acyltransferase (GNPAT) enzyme activity was found. A receiver operating characteristic (ROC) curve built for three plasmalogens of phosphatidylserine (PS), named PS(P-36:1), PS(P-38:3) and PS(P-40:5), presented an area under the curve (AUC) of 0.998, and sensitivity and specificity of 100 and 85.7% respectively. These results show significant differences in CC patients’ plasma lipid composition that may be useful in discriminating them from CTR individuals with a special role for plasmalogens.
Highlights
Colorectal cancer (CRC) accounts for 1 in 10 cancer cases and deaths worldwide and is the third pathology in terms of incidence, and second in terms of mortality [1,2]
CTR volunteers were observed according to the cancer stage for saturated FA (SFA) (14:0), which was reduced in stage II, and n-6 poly-unsaturated FA (PUFA) (20:4 n-6), which was reduced in stages III/IV
This study reports the lipidomic investigation of plasma samples from CC patients compared to CTR volunteers in order to detect putative lipid biomarkers with the potential to differentiate both groups
Summary
Colorectal cancer (CRC) accounts for 1 in 10 cancer cases and deaths worldwide and is the third pathology in terms of incidence, and second in terms of mortality [1,2]. While gas chromatography (GC) enables the qualitative and quantitative evaluation of fatty acid (FA) composition of the lipidic portion in biological samples, the use of ultra-performance liquid chromatography coupled to electrospray ionization quadrupole time-of-flight mass spectrometry operating in high energy collision spectral acquisition mode (MSE ). MSE scans enable simultaneous acquisition of full scan data and collision-induced fragmentation to improve the identification of lipid classes and to obtain structural information [10]. Mass spectrometry-based lipidomics studies have been applied to different types of cancer [11,12,13,14,15,16,17]. We used a UPLC-QTOF-MSE -based untargeted lipidomic approach to investigate differences between the lipid profiles of CC patients and those of CTR volunteers. Those findings have encouraged many endeavors to establish plasmalogens as tumor markers in medical cancer diagnostics [28]
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