Lipid profiling for early diagnosis and progression of colorectal cancer using direct‐infusion electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry

Li, Fang; Qin, Xuzhen; Chen, Haiquan; Qiu, Ling; Guo, Yumei; Liu, Hui; Chen, Guoqiang; Song, Gaoguang; Wang, Xiaodong; Li, Fenjie; Guo, Shuai; Wang, Baohua; Li, Zhili

doi:10.1002/rcm.6420

Cited by 97 publications

(75 citation statements)

References 34 publications

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“…In this review, there was evidence that metabolite modulation was discernable at very early stages of GI cancer (30,46,52,(57)(58)(59). Several studies reported incremental metabolomic changes with invasive (41,43,58,59) and metastatic (46,70,71) progression. In addition, three studies in colorectal cancer that were excluded from the appraisal process owing to their design nonetheless demonstrated pertinent findings to metabolomic dynamics.…”

Section: Discussionmentioning

confidence: 99%

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Diagnostic Metabolomic Blood Tests for Endoluminal Gastrointestinal Cancer—A Systematic Review and Assessment of Quality

Antonowicz

Kumar

Wiggins

et al. 2016

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Advances in analytics have resulted in metabolomic blood tests being developed for the detection of cancer. This systematic review aims to assess the diagnostic accuracy of blood-based metabolomic biomarkers for endoluminal gastrointestinal (GI) cancer. Using endoscopic diagnosis as a reference standard, methodologic and reporting quality was assessed using validated tools, in addition to pathway-based informatics to biologically contextualize discriminant features. Twenty-nine studies (15 colorectal, 9 esophageal, 3 gastric, and 2 mixed) with data from 10,835 participants were included. All reported significant differences in hematologic metabolites. In pooled analysis, 246 metabolites were found to be significantly different after multiplicity correction. Incremental metabolic flux with disease progression was frequently reported. Two promising candidates have been validated in independent populations (both colorectal biomarkers), and one has been approved for clinical use. Networks analysis suggested modulation of elements of up to half of Edinburgh Human Metabolic Network subdivisions, and that the poor clinical applicability of commonly modulated metabolites could be due to extensive molecular interconnectivity. Methodologic and reporting quality was assessed as moderate-to-poor. Serum metabolomics holds promise for GI cancer diagnostics; however, future efforts must adhere to consensus standardization initiatives, utilize high-resolution discovery analytics, and compare candidate biomarkers with peer nonendoscopic alternatives.Cancer Epidemiol Biomarkers Prev; 25(1); 6-15. Ó2015 AACR.

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Section: Discussionmentioning

confidence: 99%

“…Nine studies investigated esophageal cancer (39-47), 3 gastric cancer (48)(49)(50), and 15 colorectal cancer (29,30,(51)(52)(53)(54)(55)(56)(57)(58)(59)(60)(61)(62)(63). Two studies investigated more than one GI malignancy (64,65).…”

Section: Resultsmentioning

confidence: 99%

Diagnostic Metabolomic Blood Tests for Endoluminal Gastrointestinal Cancer—A Systematic Review and Assessment of Quality

Antonowicz

Kumar

Wiggins

et al. 2016

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…Some of these substances, including hexadecanedioic, octadecanoic, eicosatrienoic, and myristic acids, belong to a panel that could be used to discriminate early-stage CRC patients from healthy controls. However, the authors highlighted that further studies are required to confirm the changes in the levels of these lipids with CRC progression and to determine why these alterations occur [19]. De novo lipid synthesis and lipid metabolism are strongly regulated in cancer tissues through oncogene activation [20].…”

Section: Introductionmentioning

confidence: 95%

Altered plasma levels of decanoic acid in colorectal cancer as a new diagnostic biomarker

et al. 2016

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Colorectal cancer (CRC) is one of the most common tumors in developed countries. The five-year survival rate decreases depending on how advanced the CRC is when first diagnosed. Screening has been proven to greatly reduce mortality from colorectal cancer, but an ideal screening tool is far from being established. Here, we aimed to discover and validate early CRC biomarkers by means of an untargeted/targeted metabolomic approach. A preliminary untargeted analysis of plasma lipids performed on a small patient cohort (30 plasma samples) revealed some alterations that occurred in the presence of this tumor. In particular, medium-chain fatty acids with between six and twelve carbon atoms (C6-C12) were found to be the lipid class that showed the most marked changes upon the development of CRC. In order to evaluate the utility of this lipid class as diagnostic CRC biomarkers, a further study based on a wider cohort of patients (117 plasma samples) was performed. Using a targeted approach, these fatty acids were quantified in plasma samples by means of fast gas chromatography coupled to a time-of-flight analyzer. Plasma samples from patients with CRCs at different tumor stages were analyzed and compared to those from healthy subjects, ulcerative colitis patients, high-grade dysplasia adenoma patients, and breast cancer patients in order to test the specificity and sensitivity of these possible biomarkers. Results revealed significant differences among the considered groups in terms of their C6, C8, C10, and C12 fatty acid plasma concentrations. In particular, receiver operating characteristic (ROC) curves obtained for the C10 fatty acid gave an area under the curve of 0.8195 along with a sensitivity of 87.8 % and a specificity of 80 %, strongly suggesting that it could be a valuable early diagnostic biomarker of CRC.

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“…This hybrid quadrupole-Orbitrap-ion trap mass spectrometer is equipped with three mass analyzers, two detectors, and two collision cells enabling complementary multi-stage fragmentation analysis using both quadrupole-based higher-energy collisional dissociation (HCD) and ion trap-based resonant-excitation collision-induced dissociation (CID). The ultra-high-field mass analyzer of the Orbitrap Fusion affords acquisition of FTMS spectra with resolving power up to 450,000 (full width at half maximum (FWHM) at m/z 200) at a transient duration of 1 s. The high resolving power at this scan speed is thus far unsurpassed by any other commercially available Orbitrap instrument, and at m/z 400 comparable to that of commonly used FT-ICR mass spectrometers operated with a transient duration of 1 s, as typically used for routine analysis [17,[25][26][27]. A key benefit of high resolving power for lipidomic analysis is the ability to accurately discriminate lipid species with isobaric nominal masses as well as their isotopes and, hence, support accurate lipid identification [17,28].…”

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confidence: 99%

Comprehensive Lipidome Analysis by Shotgun Lipidomics on a Hybrid Quadrupole-Orbitrap-Linear Ion Trap Mass Spectrometer

Almeida

Pauling

Sokol

et al. 2014

J. Am. Soc. Mass Spectrom.

125

174

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Abstract. Here we report on the application of a novel shotgun lipidomics platform featuring an Orbitrap Fusion mass spectrometer equipped with an automated nanoelectrospray ion source. To assess the performance of the platform for indepth lipidome analysis, we evaluated various instrument parameters, including its high resolution power unsurpassed by any other contemporary Orbitrap instrumentation, its dynamic quantification range and its efficacy for in-depth structural characterization of molecular lipid species by quadrupole-based higher-energy collisional dissociation (HCD), and ion trap-based resonant-excitation collision-induced dissociation (CID). This evaluation demonstrated that FTMS analysis with a resolution setting of 450,000 allows distinguishing isotopes from different lipid species and features a linear dynamic quantification range of at least four orders of magnitude. Evaluation of fragmentation analysis demonstrated that combined use of HCD and CID yields complementary fragment ions of molecular lipid species. To support global lipidome analysis, we designed a method, termed MS ALL , featuring high resolution FTMS analysis for lipid quantification, and FTMS 2 analysis using both HCD and CID and ITMS 3 analysis utilizing dual CID for in-depth structural characterization of molecular glycerophospholipid species. The performance of the MS ALL method was benchmarked in a comparative analysis of mouse cerebellum and hippocampus. This analysis demonstrated extensive lipidome quantification covering 311 lipid species encompassing 20 lipid classes, and identification of 202 distinct molecular glycerophospholipid species when applying a novel high confidence filtering strategy. The work presented here validates the performance of the Orbitrap Fusion mass spectrometer for in-depth lipidome analysis.

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Lipid profiling for early diagnosis and progression of colorectal cancer using direct‐infusion electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry

Abstract: Our study revealed that the consideration of CRC stages would be necessary in diagnostic biomarker discovery, as well as that attention should be paid to the facile loss of methyl chloride from the [M + Cl](-) form of LPC(16:0) in its tandem mass spectrum.

Cited by 97 publications

References 34 publications

Diagnostic Metabolomic Blood Tests for Endoluminal Gastrointestinal Cancer—A Systematic Review and Assessment of Quality

Diagnostic Metabolomic Blood Tests for Endoluminal Gastrointestinal Cancer—A Systematic Review and Assessment of Quality

Altered plasma levels of decanoic acid in colorectal cancer as a new diagnostic biomarker

Comprehensive Lipidome Analysis by Shotgun Lipidomics on a Hybrid Quadrupole-Orbitrap-Linear Ion Trap Mass Spectrometer

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