Overexpression of HexCer and LacCer containing 2-hydroxylated fatty acids in cholangiocarcinoma and the association of the increase of LacCer (d18:1-h23:0) with shorter survival of the patients

Silsirivanit, Atit; Phoomak, Chatchai; Teeravirote, Karuntarat; Wattanavises, Sasiprapa; Seubwai, Wunchana; Saengboonmee, Charupong; Zhan, Zhaoqi; Inokuchi, Jin-ichi; Suzuki, Akemi; Wongkham, Sopit

doi:10.1007/s10719-019-09864-4

Cited by 12 publications

(12 citation statements)

References 39 publications

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“…Next, the biological significance of many lipid species is far from being understood, which prevents a comprehensive interpretation of the serum lipidome. Specifically, little or no data are available on the biological roles of GSL, LPE and LPI species [ 98 , 99 , 100 , 101 , 102 ]. In addition, the differences in lipid annotation levels also complicate data interpretation.…”

Section: Discussionmentioning

confidence: 99%

Metabolic View on Human Healthspan: A Lipidome-Wide Association Study

et al. 2021

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As ageing is a major risk factor for the development of non-communicable diseases, extending healthspan has become a medical and societal necessity. Precise lipid phenotyping that captures metabolic individuality could support healthspan extension strategies. This study applied ‘omic-scale lipid profiling to characterise sex-specific age-related differences in the serum lipidome composition of healthy humans. A subset of the COmPLETE-Health study, composed of 73 young (25.2 ± 2.6 years, 43% female) and 77 aged (73.5 ± 2.3 years, 48% female) clinically healthy individuals, was investigated, using an untargeted liquid chromatography high-resolution mass spectrometry approach. Compared to their younger counterparts, aged females and males exhibited significant higher levels in 138 and 107 lipid species representing 15 and 13 distinct subclasses, respectively. Percentage of difference ranged from 5.8% to 61.7% (females) and from 5.3% to 46.0% (males), with sphingolipid and glycerophophospholipid species displaying the greatest amplitudes. Remarkably, specific sphingolipid and glycerophospholipid species, previously described as cardiometabolically favourable, were found elevated in aged individuals. Furthermore, specific ether-glycerophospholipid and lyso-glycerophosphocholine species displayed higher levels in aged females only, revealing a more favourable lipidome evolution in females. Altogether, age determined the circulating lipidome composition, while lipid species analysis revealed additional findings that were not observed at the subclass level.

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Section: Discussionmentioning

confidence: 99%

Metabolic View on Human Healthspan: A Lipidome-Wide Association Study

et al. 2021

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Section: Introductionmentioning

confidence: 99%

“…14 Our prior research revealed elevated expression of N-linked glycoprotein glycans in serum from patients with cholangiocarcinoma, compared with healthy controls; 15 elevated glycosphingolipid levels have also been associated with shorter survival in patients with cholangiocarcinoma. 16 Because the above studies of glycolipids have not yielded sufficiently compelling biomarkers, the present study investigated the structural detail and the quantities of glycosphingolipids in serum samples from patients with cholangiocarcinoma, compared with healthy controls. The candidate glycosphingolipid biomarkers identified in this study may aid in development of cholangiocarcinoma biomarkers and their use in clinical applications.…”

Section: Introductionmentioning

confidence: 99%

Ganglioside GM2: a potential biomarker for cholangiocarcinoma

Talabnin

Kumagai

et al. 2020

J Int Med Res

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Objective To investigate the expression of glycosphingolipids in serum and tissue from patients with cholangiocarcinoma compared with healthy controls. Methods Nanospray ionization-linear ion trap mass spectrometry (NSI-MSn) was used to demonstrate the comparative structural glycomics of glycosphingolipids in serum from patients with cholangiocarcinoma (n=15), compared with healthy controls (n = 15). GM2 expression in cholangiocarcinoma tissues (n = 60) was evaluated by immunohistochemistry. Results Eleven glycosphingolipids were detected by NSI-MSn: CMH (ceramide monohexose), Lac-Cer (galactose (Gal)β1-4 glucose (Glc)β1-1'-ceramide), Gb3 (Galα1-4Galβ1-4Glcβ1-1'-ceramide), Gb4/Lc4 (N-acetylgalactosamine (GalNAc)β1-3Galα1-4Galβ1-4Glcβ1-1'-ceramide/Galβ1-4 N-acetylglucosamine (GlcNAc)β1-3Galβ1-4Glcβ1-1'-ceramide), GM3 (N-acetylneuraminic acid (NeuAc)2-3Galβ1-4Glcβ1-1'-ceramide), GM2 (GalNAcβ1-4[NeuAc2-3]Galβ1-4Glcβ1-1'-ceramide), GM1 (Galβ1-3GalNAcβ1-4[NeuAc2-3]Galβ1-4Glcβ1-1'-ceramide), hFA (hydroxylated fatty acid)-CMH, hFA-Lac-Cer, hFA-Gb3, and hFA-GM3. Lac-Cer was the most abundant structure among the lactosides and globosides (normal, 24.40% ± 0.11%; tumor, 24.61% ± 2.10%), while GM3 predominated among the gangliosides (normal, 29.14% ± 1.31%; tumor, 30.53% ± 4.04%). The two glycosphingolipids that significantly differed between healthy controls and patients with cholangiocarcinoma were Gb3 and GM2. High expression of GM2 was associated with vascular invasion in tissue from patients with cholangiocarcinoma. Conclusions Altered expression of glycosphingolipids in tissue and serum from patients with cholangiocarcinoma may contribute to tumor growth and progression. The ganglioside GM2, which significantly increased in the serum of patients with cholangiocarcinoma, represents a promising target as a biomarker for cholangiocarcinoma.

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“…Sample preparation for oxygenated lipids uses the typical strategies in lipidomics, such as organic solvent addition for protein precipitation (PPT). The organic solvent, alone or as a mixture of solvents, can be accompanied by the use of ultrasound (entries 2, 19, 41, 44) [19,63,66,45], microwave or vortex (entry 4) [33] to enhance metabolite extraction. Extraction of SP (2OH), CAR (3OH) and CAR (DC) is usually done by PPT leading to one single phase systems [4] (Table 1.…”

Section: Extraction and Concentration Methods: Protein Precipitation Liquid-liquid Extraction Solid Phase Extraction And Solid Phase Micrmentioning

confidence: 99%

“…For this approach, a highresolution MS (HRMS) platform is necessary to determine the exact mass and thereby discriminate each lipid species. QTOF (entry 22) [26], ion trap-TOF (IT-TOF; entry 4) [33], Orbitrap (entry 34) [23], and Fourier transform ion cyclotron resonance (FT-ICR; entry 21) [47] mass spectrometers have been mainly used.…”

Section: Non-targeted Analysismentioning

confidence: 99%

Analytical approaches for studying oxygenated lipids in the search of potential biomarkers by LC-MS

Villaseñor

Godzień

Barker-Tejeda

et al. 2021

TrAC Trends in Analytical Chemistry

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Great advances in lipidomics during the last years have opened the door to a broader knowledge of oxygenated lipids. These substances are derived either from the inclusion of previously hydroxylated fatty acids in the lipid structure of sphingolipids and acyl-L-carnitines, or by enzymatic and nonenzymatic modifications (oxidized lipids) of glycerophospholipids (including cardiolipins), cholesteryl esters and cholesterol. Despite their significance in the regulation of multiple diseases such as cancer or diabetes, the number of experimentally detected oxygenated lipids remains relatively low. This is in part due to the main challenges in their analysis, which are their low natural concentrations, their wide diversity of physicochemical properties, presence of isomers, and their a priori unknown presence in the biological samples. In particular, analysis of oxidized lipids, especially peroxides, has become a daunting task in liquid chromatography coupled to mass spectrometry (LC-MS) due to their high chemical and thermal instability, and the potential for further propagation of lipid oxidation and eventual degradation. The aim of this review is to highlight the experimental conditions on sample preparation procedures, the LC-MS based analytical approaches for identification and quantification of oxygenated lipids, and their relation as potential biomarkers in diseases based on the most relevant articles published in the last five years. Regarding sample preparation, special attention has been given to antioxidants, internal standards, extraction and concentration methods, and derivatization approaches. Moreover, targeted, semi-targeted and non-targeted strategies have been discussed presenting examples. Finally, considerations on the structural identification, one of the main challenges, are presented.

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Overexpression of HexCer and LacCer containing 2-hydroxylated fatty acids in cholangiocarcinoma and the association of the increase of LacCer (d18:1-h23:0) with shorter survival of the patients

Cited by 12 publications

References 39 publications

Metabolic View on Human Healthspan: A Lipidome-Wide Association Study

Metabolic View on Human Healthspan: A Lipidome-Wide Association Study

Ganglioside GM2: a potential biomarker for cholangiocarcinoma

Analytical approaches for studying oxygenated lipids in the search of potential biomarkers by LC-MS

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