Reduced Plasma Levels of Very-Long-Chain Dicarboxylic Acid 28:4 in Italian and Brazilian Colorectal Cancer Patient Cohorts

Wood, Paul L.; Donohue, Michelle M.; Cebak, John E.; Beckmann, Taylor; Messias, Márcia Cristina Fernandes; Credidio, Laura; Coy, Cláudio Saddy Rodrigues; Carvalho, Patrícia de Oliveira; Crotti, Sara; DaRonco, S.; Urso, Emanuele; Agostini, Marco

doi:10.3390/metabo8040091

Cited by 6 publications

(3 citation statements)

References 23 publications

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“…18 Recent data in support of this view have been published, highlighting that decrements in plasma levels of the very-long-chain dicarboxylic acid (28:4), a potent anti-inflammatory molecule, are detectable in CRC patients, and not in FAP patients. 21 In order to verify whether inflammatory cytokines may be associated to sporadic CRC and not to FAP, we performed the simultaneous detection of pro-inflammatory cytokines (or chemokines) in a new cohort of patients. To do this, IL1α, IL1β, IL2, IL6, IL8, IL10, IL12, IL17A, IFNγ, TNFα, and GM-CSF have been quantified in 50 µL of serum samples of ADE (n = 6), CRC (n = 8), and FAP (n = 4).…”

Section: Resultsmentioning

confidence: 99%

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Tryptophan Metabolism as Source of New Prognostic Biomarkers for FAP Patients

Crotti

Bedin

Bertazzo

et al. 2019

Int J�Tryptophan�Res

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Familial adenomatous polyposis (FAP), a common inherited form of colorectal cancer (CRC), causes the development of hundreds to thousands of colonic adenomas in the colorectum beginning in early adolescence. In absence of a prophylactic surgery, FAP patients almost inevitably develop CRC by the age of 40 to 50. The lack of valuable prognostic biomarkers for FAP patients makes it difficult to predict when the progression from adenoma to malignant carcinoma occurs. Decreased tryptophan (TRP) plasma levels and increased indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan hydroxylase 1 (TPH1) enzymatic activities have been associated to tumour progression in CRC. In the present study, we aimed at investigating whether an altered TRP metabolism might also exist in FAP patients. Our results highlighted that plasma levels of TRP and its main catabolites are comparable between FAP patients and healthy subject. On the contrary, FAP patients presented significantly higher TRP levels with respect to high-grade adenoma (ADE) subjects and CRC patients. Obtained data lead us to evaluate IDO1 and TPH1 enzymes activity in the study groups. For both enzymes, it was possible to discriminate correctly between FAP subject and ADE/CRC patients with high sensitivities and specificities. By receiver operating characteristic (ROC) curve analysis, the cut-off values of IDO1 and TPH1 enzymatic activities associated to the presence of an active malignant transformation have been calculated as >38 and >5.5, respectively. When these cut-off values are employed, the area under the curve (AUC) is > 0.8 for both, indicating that TRP metabolism in patients with FAP may be used to monitor and predict the tumorigenic evolution.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Tryptophan Metabolism as Source of New Prognostic Biomarkers for FAP Patients

Crotti

Bedin

Bertazzo

et al. 2019

Int J�Tryptophan�Res

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“…Lipid peroxidation with the formation of reactive compounds, such as malonaldehyde, hexanal, and 4-hydroxynonenal, leads to changes in the permeability and fluidity of the membrane lipid bilayer altering cell integrity [55] and has been described as an important determinant of cancer cell function [56,57]. Preliminary data have also reported lower 3-PUFA content in plasma samples of CRC [58] and rectal adenocarcinoma patients [17], as well as a decrease in very-long-chain dicarboxylic acid 28:4 in plasma levels from Italian and Brazilian CRC patient cohorts [59].…”

Section: Discussionmentioning

confidence: 99%

Plasma Lipid Profile Reveals Plasmalogens as Potential Biomarkers for Colon Cancer Screening

et al. 2020

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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.

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