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

Abstract

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.

This is a preview of subscription content, log in to check access.

Fig. 1
Fig. 2
Fig. 3a–b

References

  1. 1.

    Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J, Rosso S, Coebergh JW, Comber H, et al. Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012. Eur J Cancer. 2013;49(6):1374–403.

    CAS  Article  Google Scholar 

  2. 2.

    Adler A, Geiger S, Keil A, Bias H, Schatz P, deVos T, et al. Improving compliance to colorectal cancer screening using blood and stool based tests in patients refusing screening colonoscopy in Germany. BMC Gastroenterol. 2014;14(1):183.

    Article  Google Scholar 

  3. 3.

    Zhang A, Yan G, Han Y, Wang X. Metabolomics approaches and applications in prostate cancer research. Appl Biochem Biotechnol. 2014;174(1):6–12.

    CAS  Article  Google Scholar 

  4. 4.

    Deja S, Porebska I, Kowal A, Zabek A, Barg W, Pawelczyk K, et al. Metabolomics provide new insights on lung cancer staging and discrimination from chronic obstructive pulmonary disease. J Pharm Biomed Anal. 2014;100:369–80.

    CAS  Article  Google Scholar 

  5. 5.

    Ke C, Hou Y, Zhang H, Fan L, Ge T, Guo B, et al. Large-scale profiling of metabolic dysregulation in ovarian cancer. Int J Cancer. 2015;136(3):516–26.

    CAS  Google Scholar 

  6. 6.

    Dettmer K, Hammock BD. Metabolomics—a new exciting field within the “omics” sciences. Environ Health Perspect. 2004;112(7):A396–7.

  7. 7.

    Watson AD. Thematic review series: systems biology approaches to metabolic and cardiovascular disorders. lipidomics: a global approach to lipid analysis in biological systems. J Lipid Res. 2006;47(10):2101–11.

    CAS  Article  Google Scholar 

  8. 8.

    Kaddurah-Daouk R, Kristal BS, Weinshilboum RM. Metabolomics: a global biochemical approach to drug response and disease. Annu Rev Pharmacol. 2008;48:653–83.

    CAS  Article  Google Scholar 

  9. 9.

    Nkondjock A, Shatenstein B, Maisonneuve P, Ghadirian P. Specific fatty acids and human colorectal cancer: an overview. Cancer Detect Prev. 2003;27(1):55–66.

    CAS  Article  Google Scholar 

  10. 10.

    Slattery ML, Benson J, Ma KN, Schaffer D, Potter JD. Trans-fatty acids and colon cancer. Nutr Cancer. 2001;39(2):170–5.

    CAS  Article  Google Scholar 

  11. 11.

    Cottet V, Vaysse C, Scherrer ML, Ortega-Deballon P, Lakkis Z, Delhorme JB, et al. Fatty acid composition of adipose tissue and colorectal cancer: a case-control study. Am J Clin Nutr. 2015;101(1):192–201.

    CAS  Article  Google Scholar 

  12. 12.

    Szachowicz-Petelska B, Sulkowski S, Figaszewski ZA. Altered membrane free unsaturated fatty acid composition in human colorectal cancer tissue. Mol Cell Biochem. 2007;294(1-2):237–42.

    CAS  Article  Google Scholar 

  13. 13.

    Hietanen E, Bartsch H, Bereziat JC, Camus AM, McClinton S, Eremin O, et al. Diet and oxidative stress in breast, colon and prostate cancer patients: a case-control study. Eur J Clin Nutr. 1994;48(8):575–86.

    CAS  Google Scholar 

  14. 14.

    Baro L, Hermoso JC, Nunez MC, Jimenez-Rios JA, Gil A. Abnormalities in plasma and red blood cell fatty acid profiles of patients with colorectal cancer. Br J Cancer. 1998;77(11):1978–83.

    CAS  Article  Google Scholar 

  15. 15.

    Kenyon MA, Hamilton JA. 13C NMR studies of the binding of medium-chain fatty acids to human serum albumin. J Lipid Res. 1994;35(3):458–67.

    CAS  Google Scholar 

  16. 16.

    Vorum H, Pedersen AO, Honore B. Fatty acid and drug binding to a low-affinity component of human serum albumin, purified by affinity chromatography. Int J Pept Protein Res. 1992;40(5):415–22.

    CAS  Article  Google Scholar 

  17. 17.

    Nagao K, Yanagita T. Medium-chain fatty acids: functional lipids for the prevention and treatment of the metabolic syndrome. Pharmacol Res. 2010;61(3):208–12.

    CAS  Article  Google Scholar 

  18. 18.

    Papamandjaris AA, MacDougall DE, Jones PJ. Medium chain fatty acid metabolism and energy expenditure: obesity treatment implications. Life Sci. 1998;62(14):1203–15.

    CAS  Article  Google Scholar 

  19. 19.

    Li F, Qin XZ, Chen HQ, Qiu L, Guo YM, Liu H, et al. Lipid profiling for early diagnosis and progression of colorectal cancer using direct-infusion electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry. Rapid Commun Mass Sp. 2013;27(1):24–34.

    Article  Google Scholar 

  20. 20.

    Zhang F, Du G. Dysregulated lipid metabolism in cancer. World J Biol Chem. 2012;3(8):167–74.

    Article  Google Scholar 

  21. 21.

    Rashid A, Pizer ES, Moga M, Milgraum LZ, Zahurak M, Pasternack GR, et al. Elevated expression of fatty acid synthase and fatty acid synthetic activity in colorectal neoplasia. Am J Pathol. 1997;150(1):201–8.

    CAS  Google Scholar 

  22. 22.

    Folch J, Lees M, Sloane Stanley GH. A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem. 1957;226(1):497–509.

    CAS  Google Scholar 

  23. 23.

    Neoptolemos JP, Clayton H, Heagerty AM, Nicholson MJ, Johnson B, Mason J, et al. Dietary fat in relation to fatty acid composition of red cells and adipose tissue in colorectal cancer. Br J Cancer. 1988;58(5):575–9.

    CAS  Article  Google Scholar 

  24. 24.

    Schloss I, Kidd MS, Tichelaar HY, Young GO, O’Keefe SJ. Dietary factors associated with a low risk of colon cancer in coloured West Coast fishermen. S Afr Med J. 1997;87(2):152–8.

  25. 25.

    Slattery ML, Potter JD, Duncan DM, Berry TD. Dietary fats and colon cancer: assessment of risk associated with specific fatty acids. Int J Cancer. 1997;73(5):670–7.

    CAS  Article  Google Scholar 

  26. 26.

    EMA. European Medicines Agency guideline on bioanalytical method validation. EMEA/CHMP/EWP/192217/2009 Rev 1. London: European Medicines Agency; 2011.

  27. 27.

    US FDA. US Food and Drug Administration guidance for industry: bioanalytical method validation. Silver Spring, MD: US FDA; 2001.

  28. 28.

    Toll AD, Fabius D, Hyslop T, Pequignot E, DiMarino AJ, Infantolino A, et al. Prognostic significance of high-grade dysplasia in colorectal adenomas. Colorectal Dis. 2011;13(4):370–3.

    CAS  Article  Google Scholar 

Download references

Acknowledgments

This work was supported by the Associazione Italiana per la Ricerca sul Cancro (AIRC), “Progetto Regionale Speciale: Veneto 2010–2014,” and by funding from Ricerca Finalizzata of the Italian Healthcare Ministry (grant code number: RF-2011-02349645). The authors would like to thank U. Saini and M.S. Klee (DANI Instruments S.A.) for their support.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Sara Crotti.

Ethics declarations

This study was conducted according to the principles expressed in the Declaration of Helsinki. All blood samples were collected under the full ethical approval of the ethics committee and only after informed consent had been obtained from all of the patients enrolled in the study.

Conflict of interest

None.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Crotti, S., Agnoletto, E., Cancemi, G. et al. Altered plasma levels of decanoic acid in colorectal cancer as a new diagnostic biomarker. Anal Bioanal Chem 408, 6321–6328 (2016). https://doi.org/10.1007/s00216-016-9743-1

Download citation

Keywords

  • Colorectal cancer
  • Biomarkers
  • Free fatty acids
  • GC-MS