Untargeted Metabolomics Reveals Major Differences in the Plasma Metabolome between Colorectal Cancer and Colorectal Adenomas

Gumpenberger, Tanja; Brezina, Stefanie; Keski‐Rahkonen, Pekka; Baierl, Andreas; Robinot, Nivonirina; Leeb, Gernot; Habermann, Nina; Kok, Dieuwertje E.; Scalbert, Augustin; Ueland, Per Magne; Ulrich, Cornelia M.; Gsur, Andrea

doi:10.3390/metabo11020119

Cited by 24 publications

(28 citation statements)

References 52 publications

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“…Twenty-one studies compared CRC directly to healthy control [24][25][26]31,33,36,38,39,[42][43][44][45][46][48][49][50][51][52][53][54]56]. Jing et al and Gao et al, conversely, compared CRC patients to an adenomatous polyp control [32,55] while eleven studies utilized CRC, healthy control, and adenomatous polyp groups [28][29][30]34,35,37,40,41,47,57,58]. Two studies (Geijson et al, Liu et al) did not include a control group [22,23], while Di Giovanni et al compared CRC groups to healthy control in both CRC models as well as CRC remission models, using separate controls but comparing CRC-remission and CRC patients using an Effect Size model [27].…”

Section: Study Design and Population Characteristicsmentioning

confidence: 99%

The Application of Metabolomics in Recent Colorectal Cancer Studies: A State-of-the-Art Review

Gold

Choueiry

Jin

et al. 2022

Cancers

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Colorectal cancer (CRC) is a highly prevalent disease with poor prognostic outcomes if not diagnosed in early stages. Current diagnosis techniques are either highly invasive or lack sufficient sensitivity. Thus, identifying diagnostic biomarkers of CRC with high sensitivity and specificity is desirable. Metabolomics represents an analytical profiling technique with great promise in identifying such biomarkers and typically represents a close tie with the phenotype of a specific disease. We thus conducted a systematic review of studies reported from January 2012 to July 2021 relating to the detection of CRC biomarkers through metabolomics to provide a collection of knowledge for future diagnostic development. We identified thirty-seven metabolomics studies characterizing CRC, many of which provided metabolites/metabolic profile-based diagnostic models with high sensitivity and specificity. These studies demonstrated that a great number of metabolites can be differentially regulated in CRC patients compared to healthy controls, adenomatous polyps, or across stages of CRC. Among these metabolite biomarkers, especially dysregulated were certain amino acids, fatty acids, and lysophosphatidylcholines. Additionally, we discussed the contribution of the gut bacterial population to pathogenesis of CRC through their modulation to fecal metabolite pools and summarized the established links in the literature between certain microbial genera and altered metabolite levels in CRC patients. Taken together, we conclude that metabolomics presents itself as a promising and effective method of CRC biomarker detection.

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Section: Study Design and Population Characteristicsmentioning

confidence: 99%

The Application of Metabolomics in Recent Colorectal Cancer Studies: A State-of-the-Art Review

Gold

Choueiry

Jin

et al. 2022

Cancers

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“…Another study based on stool metabolomics showed that combination of Cer 18:1, Cer 18:2, Cer 20:4, PE 16:0/18:1, SM d18:1/23:0, SM 42:3, and TAG 54:1 could effectively discriminate NR and CRC as the diagnostic biomarker, and its integrated performance was good (AUC = 0.821) (30). In the plasma metabolomics, 48 differential metabolites were uncovered between CA and CRC, mainly including LPCs and PCs, and both of them were down-regulated in CRC (31). In tissue metabolomics, PC 32:1 was suggested as an invaluable biomarker, which could be used for clinical diagnosis for CRC by imaging mass spectrometry (32).…”

Section: Discussionmentioning

confidence: 93%

Serum untargeted lipidomics by UHPLC-ESI -HRMS aids the biomarker discovery of colorectal adenoma

Zhang

Zhou

Nong

et al. 2022

Preprint

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Background: Colorectal adenoma (CA) is an important precancerous lesion and early screening target of colorectal cancer (CRC). Lipids with numerous physiological functions are proved to be involved in the development of CRC. However, there is no lipidomic study with large-scale serum samples on diagnostic biomarkers for CA.Methods: The serum lipidomics of CA patients (n = 50) and normal control (NR) (n = 50) was performed by ultra high performance liquid chromatography-high resolution mass spectrometry with electrospray ionization (UHPLC-ESI-HRMS). Univariate and multivariate statistical analyses were utilized to screen the differential lipids between groups, and combining the constituent ratio analysis and diagnostic efficiency evaluation by receiver operating characteristic curve (ROC) disclosed the potential mechanism and biomarkers for CA.Results: There were obvious differences in serum lipid profiles between CA and NR groups. Totally, 79 differential lipids were select by criterion of P < 0.05 and fold change > 1.5 or < 0.67. Triacylglycerols (TAGs) and phosphatidylcholines (PCs) were the major differential lipids with ratio > 60%, indicating these two lipid metabolic pathways showed evident disequilibrium, which could contribute to CA formation. Of them, 12 differential lipids had good diagnostic ability as candidate biomarkers for CA (AUC ≥ 0.900) by ROC analysis. Conclusions: To our knowledge, this is the first attempt to profile serum lipidomics and explore lipid biomarkers of CA to help early screening of CRC. 12 differential lipids are obtained to act as potential diagnostic markers of CA. PCs and fatty acids were the main dysregulated biomarkers for CA in serum.

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“…LPEPS oral administration decreased 3-hydroxynonanoyl carnitine in the AOM/DSS-treated mice. A number of studies have shown that carnitine was enriched in colon cancer and type 2 diabetes [ 46 , 55 , 56 , 57 , 58 ], while natural active substance supplementation effectively decreased concentration of carnitine in type 2 diabetes [ 46 , 50 ].…”

Section: Discussionmentioning

confidence: 99%

Exopolysaccharide Produced by Lactiplantibacillus plantarum-12 Alleviates Intestinal Inflammation and Colon Cancer Symptoms by Modulating the Gut Microbiome and Metabolites of C57BL/6 Mice Treated by Azoxymethane/Dextran Sulfate Sodium Salt

Song

Sun

et al. 2021

Foods

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Exopolysaccharide produced by Lactiplantibacillus plantarum-12 (LPEPS) exhibited the anti-proliferating effect on human colon cancer cell line HT-29 in vitro. The purpose of the study was to determine the alleviating effects of LPEPS on colon cancer development of the C57BL/6 mice treated by azoxymethane/dextran sulfate sodium salt (AOM/DSS). The C57BL/6 mice treated by AOM/DSS were orally administered LPEPS daily for 85 days. The results showed that LPEPS oral administration enhanced colon tight-junction protein expression and ameliorated colon shortening and tumor burden of the AOM/DSS treated mice. Furthermore, LPEPS oral administration significantly reduced pro-inflammatory factors TNF-α, IL-8, and IL-1β levels and increased anti-inflammatory factor IL-10 level in the serum of the AOM/DSS-treated mice. LPEPS oral administration reversed the alterations of gut flora in AOM/DSS-treated mice, as evidenced by the increasing of the abundance of Bacteroidetes, Bacteroidetes/Firmicutes ratio, Muribaculaceae, Burkholderiaceae, and norank_o__Rhodospirillales and the decreasing of the abundance of Firmicutes, Desulfovibrionaceae, Erysipelotrichaceae, and Helicobacteraceae. The fecal metabolites of the AOM/DSS-treated mice were altered by LPEPS oral administration, involving lipid metabolism and amino acid metabolism. Together, these results suggested that LPEPS oral administration alleviated AOM/DSS-induced colon cancer symptoms of the C57BL/6 mice by modulating gut microbiota and metabolites, enhancing intestine barrier, inhibiting NF-κB pathway, and activating caspase cascade.

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Untargeted Metabolomics Reveals Major Differences in the Plasma Metabolome between Colorectal Cancer and Colorectal Adenomas

Cited by 24 publications

References 52 publications

The Application of Metabolomics in Recent Colorectal Cancer Studies: A State-of-the-Art Review

The Application of Metabolomics in Recent Colorectal Cancer Studies: A State-of-the-Art Review

Serum untargeted lipidomics by UHPLC-ESI -HRMS aids the biomarker discovery of colorectal adenoma

Exopolysaccharide Produced by Lactiplantibacillus plantarum-12 Alleviates Intestinal Inflammation and Colon Cancer Symptoms by Modulating the Gut Microbiome and Metabolites of C57BL/6 Mice Treated by Azoxymethane/Dextran Sulfate Sodium Salt

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