Metabolomic Exploration of Colorectal Cancer Through Amino Acids and Acylcarnitines Profiling of Serum Samples

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2025 Feb 13

PMID 39941796

Authors

Lucretia Avram

Dana Crisan

Radu-Cristian Moldovan

Luisa-Gabriela Bogos

Cristina-Adela Iuga

David Andras

Sorin Crisan

Constantin Bodolea

Andrada Nemes

Valer Donca

Affiliations

Soon will be listed here.

Abstract

Background/objectives: Colorectal cancer (CRC) represents one of the most prevalent forms of cancer, with high mortality rates. The aim of this study was to observe and understand the metabolic changes in CRC through targeted metabolomics.

Methods: Samples collected from 58 CRC patients and 35 healthy individuals have been analyzed by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS), targeting two classes of metabolites: amino acids and acylcarnitines.

Results: Statistical analysis revealed 26 significantly modified (-value < 0.01; |FC| > 1.2) metabolites in CRC patients compared to the control group and 22 between colon cancer and control, whereas 8 metabolites differed only significantly between rectal cancer and healthy patients. Some of these significantly modified metabolites characterize cancer-specific adaptations, such as increased energy demand, increased tumor invasiveness, capabilities to promote amino acid synthesis, and tumor resistance against acute immune response. Moreover, receiver operator characteristic (ROC) analysis revealed that a set of two acylcarnitines (C6DC and C4-OH) can differentiate between CRC patients and healthy individuals with a high degree of confidence (AUC 0.837).

Conclusions: By implementing a metabolomics approach targeting amino acids and acylcarnitines, several metabolic alterations induced by CRC have been highlighted. Even though these modifications are not specific enough to act as disease markers, they might prove useful for evaluating patient status.

References

Ni Y, Xie G, Jia W . Metabonomics of human colorectal cancer: new approaches for early diagnosis and biomarker discovery. J Proteome Res. 2014; 13(9):3857-70. DOI: 10.1021/pr500443c. View

Bray F, Laversanne M, Sung H, Ferlay J, Siegel R, Soerjomataram I . Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024; 74(3):229-263. DOI: 10.3322/caac.21834. View

Ivanisevic J, Want E . From Samples to Insights into Metabolism: Uncovering Biologically Relevant Information in LC-HRMS Metabolomics Data. Metabolites. 2019; 9(12). PMC: 6950334. DOI: 10.3390/metabo9120308. View

Shah S, Bain J, Muehlbauer M, Stevens R, Crosslin D, Haynes C . Association of a peripheral blood metabolic profile with coronary artery disease and risk of subsequent cardiovascular events. Circ Cardiovasc Genet. 2010; 3(2):207-14. DOI: 10.1161/CIRCGENETICS.109.852814. View

Scott D, Clinton Frazee 3rd C, Heese B, Garg U . Tandem Mass Spectrometry for the Analysis of Plasma/Serum Acylcarnitines for the Diagnosis of Certain Organic Acidurias and Fatty Acid Oxidation Disorders. Methods Mol Biol. 2022; 2546:27-34. DOI: 10.1007/978-1-0716-2565-1_3. View

Erben V, Bhardwaj M, Schrotz-King P, Brenner H . Metabolomics Biomarkers for Detection of Colorectal Neoplasms: A Systematic Review. Cancers (Basel). 2018; 10(8). PMC: 6116151. DOI: 10.3390/cancers10080246. View

Kang C, Zhang J, Xue M, Li X, Ding D, Wang Y . Metabolomics analyses of cancer tissue from patients with colorectal cancer. Mol Med Rep. 2023; 28(5). PMC: 10568249. DOI: 10.3892/mmr.2023.13106. View

Ribel-Madsen A, Ribel-Madsen R, Brons C, Newgard C, Vaag A, Hellgren L . Plasma acylcarnitine profiling indicates increased fatty acid oxidation relative to tricarboxylic acid cycle capacity in young, healthy low birth weight men. Physiol Rep. 2016; 4(19). PMC: 5064135. DOI: 10.14814/phy2.12977. View

Xia C, Dong X, Li H, Cao M, Sun D, He S . Cancer statistics in China and United States, 2022: profiles, trends, and determinants. Chin Med J (Engl). 2022; 135(5):584-590. PMC: 8920425. DOI: 10.1097/CM9.0000000000002108. View

10.

Zhang W, Zhang L, Yao H, Wang Y, Zhang X, Shang L . Long-chain dicarboxylic acids play a critical role in inducing peroxisomal β-oxidation and hepatic triacylglycerol accumulation. J Biol Chem. 2023; 299(9):105174. PMC: 10494467. DOI: 10.1016/j.jbc.2023.105174. View

11.

Du T, Han J . Arginine Metabolism and Its Potential in Treatment of Colorectal Cancer. Front Cell Dev Biol. 2021; 9:658861. PMC: 8172978. DOI: 10.3389/fcell.2021.658861. View

12.

McCann M, De la Rosa M, Rosania G, Stringer K . L-Carnitine and Acylcarnitines: Mitochondrial Biomarkers for Precision Medicine. Metabolites. 2021; 11(1). PMC: 7829830. DOI: 10.3390/metabo11010051. View

13.

Wishart D . Emerging applications of metabolomics in drug discovery and precision medicine. Nat Rev Drug Discov. 2016; 15(7):473-84. DOI: 10.1038/nrd.2016.32. View

14.

Dillon B, Prieto V, Curley S, Ensor C, Holtsberg F, Bomalaski J . Incidence and distribution of argininosuccinate synthetase deficiency in human cancers: a method for identifying cancers sensitive to arginine deprivation. Cancer. 2004; 100(4):826-33. DOI: 10.1002/cncr.20057. View

15.

Tuncel A, Boy N, Morath M, Horster F, Mutze U, Kolker S . Organic acidurias in adults: late complications and management. J Inherit Metab Dis. 2018; 41(5):765-776. DOI: 10.1007/s10545-017-0135-2. View

16.

Chen Z, Berquez M, Luciani A . Mitochondria, mitophagy, and metabolic disease: towards assembling the puzzle. Cell Stress. 2020; 4(6):147-150. PMC: 7278521. DOI: 10.15698/cst2020.06.222. View

17.

Khare T, Khare S, Angdisen J, Zhang Q, Stuckel A, Mooney B . Defects in long-chain 3-hydroxy acyl-CoA dehydrogenase lead to hepatocellular carcinoma: A novel etiology of hepatocellular carcinoma. Int J Cancer. 2020; 147(5):1461-1473. DOI: 10.1002/ijc.32943. View

18.

Gold A, Choueiry F, Jin N, Mo X, Zhu J . The Application of Metabolomics in Recent Colorectal Cancer Studies: A State-of-the-Art Review. Cancers (Basel). 2022; 14(3). PMC: 8833341. DOI: 10.3390/cancers14030725. View

19.

Dambrova M, Makrecka-Kuka M, Kuka J, Vilskersts R, Nordberg D, Attwood M . Acylcarnitines: Nomenclature, Biomarkers, Therapeutic Potential, Drug Targets, and Clinical Trials. Pharmacol Rev. 2022; 74(3):506-551. DOI: 10.1124/pharmrev.121.000408. View

20.

Youm Y, Nguyen K, Grant R, Goldberg E, Bodogai M, Kim D . The ketone metabolite β-hydroxybutyrate blocks NLRP3 inflammasome-mediated inflammatory disease. Nat Med. 2015; 21(3):263-9. PMC: 4352123. DOI: 10.1038/nm.3804. View