Differences in fatty acid profi les of erythrocyte membranes related to tumor localization in colorectal cancer (pilot study)

Aim of work is to study the compositional features of fatty acids (FA) of erythrocyte membranes in patients with diff erent localization of the tumor in colorectal cancer (CRC).

Materials and methods. Using a chromatography-mass spectrometric system (GC/MS) Agilent 7000B based on three quadrupoles (USA), the composition of erythrocyte (Er) membranes of 129 patients with CRC was studied: (average age 63.2±9.4 years, of which 68 men and 61 women; 25 with proximal, 98 with distal tumor localization) and 35 people in the comparison group.

Results. A greater degree of decrease in the levels of saturated, monounsaturated FAs (MUFAs), and, conversely, an increase in the levels of polyunsaturated FAs (PUFAs) in patients with distal tumor localization compared to healthy ones, was established than the same ratio in the pair “proximal localization of tumor RCC — healthy”. A greater degree of increase in the level of omega-3 PUFAs was noted than omega-6, which aff ected the ratio n-6 / n-3, which was signifi cantly reduced in cancer patients, to a greater extent with distal tumor localization.
The most signifi cant for distinguishing tumors located in diff erent parts of the intestine were: saturated fatty acids — myristic C14:0 (p<0,001) and pentadecanoic C15:0 (p=0,012), omega-3 a-linolenic (C18:3; n-3) (p=0,02), whose levels were signifi cantly higher and, conversely, most of the omega-6 PUFAs (C18:2 n-6, C20:3 n-6, C20:4 n-6) and one omega-3 PUFAs — C22:6 n-3 (p<0,05), whose levels were signifi cantly lower with proximal localization of the tumor than with distal.

Conclusion. The results obtained indicate the importance of taking into account the localization of the tumor in patients with CRC when conducti ng studies of metabolic profiles. 

1. Bufill J. A. Colorectal cancer: evidence for distinct genetic categories based on proximal or distal tumor location. Ann. Intern. Med, 1990, Vol. 113, No. 10, pp. 779–788.

2. Li F., Lai M. Colorectal cancer, one entity or three. J. ZheJiang Univ. Sci. B. 2009, Vol. 10, No. 3, pp. 219–229. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2650032/

3. Glade M. J. Food, nutrition, and the prevention of cancer: a global perspective. American Institute for Cancer Research World Cancer Research Fund, American Institute for Cancer Research, 1997. Nutrition, 1999, Vol. 15, No. 6, pp. 523–526.

4. Sasazuki S., Inoue M., Iwasaki M., Sawada N., Shimazu T., Yamaji T., et al. Intake of n-3 and n-6 polyunsaturated fatty acids and development of colorectal cancer by sub-site: Japan Public Health Center-based prospective study. Int. J. Cancer, 2011, Vol. 129, no. 7, P. 1718–1729.

5. Hodge A. M., Williamson E. J., Bassett J. K., MacInnis R. J., Giles G. G., English D. R. Dietary and biomarker estimates of fatty acids and risk of colorectal cancer. Int. J. Cancer, 2015, Vol. 137, no. 5, P. 1224–1234.

6. Baro L., Hermoso J. C., Nunez M. C., Jimenez-Rios J. A., et al. Abnormalities in plasma and red blood cell fatty acid profi les of patients with colorectal cancer. Br. J. Cancer. 1998, Vol. 77, pp. 1978–1983.

7. Qiu Y., Cai G., Su M., Chen T., Zheng X., Xu Y., Ni Y., Zhao A., Xu L. X., Cai S., Jia W. Serum metabolite profi ling of human colorectal cancer using GC-TOFMS and UPLC-QTOFMS. J. Proteome Res. 2009, Vol. 8, no. 10, pp. 4844–4850.

8. Kondo Y., Nishiumi S., Shinohara M., Hatano N., Ikeda A., Yoshie T. Serum fatty acid profi ling of colorectal cancer by gas chromatography mass spectrometry. Biomark. Med. 2011, Vol. 5, no. 4, pp. 451–460.

9. Li F., Qin X., Chen H., Qiu L. et al. Lipid profi ling for early diagnosis and progression of colorectal cancer using direct-infusion electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry. Rapid Commun. Mass Spectrom, 2013, Vol. 27, pp. 24–34.

10. Farshidfaret F., Weljie A. M., Kopciuk K., et al. Serum metabolomic profi le as a means to distinguish stage of colorectal cancer. Genome Medicine. 2012, Vol. 4, pp. 42–49.

11. Amézaga J., Arranz S., Urruticoechea A., et al. Altered Red Blood Cell Membrane Fatty Acid Profi le in Cancer Patients. Nutrients. 2018, Vol. 10, no. 12, pp. E1853(6).

12. Okuno M., Hamazaki K., Ogura T., Kitade H. et al. Abnormalities in Fatty Acids in Plasma, Erythrocytes and Adipose Tissue in Japanese Patients with Colorectal Cancer. In Vivo. 2013. Vol. 27, pp. 203–210.

13. Zhang P., Wen X., Gu F., Zhang X. et al. Role of serum polyunsaturated fatty acids in the development of colorectal cancer. Int. J. Clin. Exp. Med. 2015. Vol. 8, no. 9, pp. 15900–15909.

14. Arab L., Akbar J. Biomarkers and the measurement of fatty acids. Public Health Nutr. 2002, Vol. 5, pp. 865–871.

15. Kruchinina M. V., Kruchinin V. N., Prudnikova Ya.I., Gromov A. A., Shashkov M. V., Sokolova A. S. Study of the level of fatty acids of erythrocyte membranes and blood serum in patients with colorectal cancer g Novosibirsk. Advances in molecular oncology. 2018.;5(2):50–61.

16. Katan M. B., van Birgelen A., Deslypere J. P., Penders M., van Staveren W. A. Biological markers of dietary intake, with emphasis on fatty acids. Ann. Nutr. Metab. 1991, Vol. 35, pp. 249–252.

17. Podkamenev A. V., Kozlov Yu.A., Pavlov A. V. Obstruction of the gastrointestinal tract in children Moscow. GEOTAR-Media, 2017. 752 p.

18. Liang X., Bittinger K., Li X., Abernethy D. R., Bushman F. D., FitzGerald G. A. Bidirectional interactions between indomethacin and the murine intestinal microbiota. eLife. 2015, Vol. 4, pp. e08973(7).

19. Jia H. J., Zhang P. J., Liu Y. L., Jiang C. G., Zhu X., Tian Y. P. Relationship of serum polyunsaturated fatty acids with cytokines in colorectal cancer. World Journal of Gastroenterology. 2016, Vol. 22, no. 8, pp. 2524–2532.

20. Bultman S. J. Interplay between diet, gut microbiota, epigenetic events, and colorectal cancer. Mol. Nutr. Food Res. 2017, Vol. 61, pp. 1–12.

21. Yachida S., Mizutani S., Shiroma H., et al. Metagenomic and metabolomic analyses reveal distinct stage-specific phenotypes of the gut microbiota in colorectal cancer. Nat. Med. 2019, Vol. 25, no. 6, pp. 968–976.

22. Alhinai E. A., Walton G. E., Commane D. M. The Role of the Gut Microbiota in Colorectal Cancer Causation. Int. J. Mol. Sci. 2019, Vol. 20, pp. 21–29.

23. Bae J. M., Kim J. H., Cho N. Y., Kim T., Kang G. H. Prognostic implication of the CpG island methylator phenotype in colorectal cancers depends on tumour location. British Journal of Cancer. 2019, V. 109, no. 4, pp.1004–1012.

24. Yan G., Li L., Zhu B., Li Y. Lipidome in colorectal cancer. Oncotarget. 2016, Vol. 7, pp. 33429–33439.

25. Bugajska J., Berska J., Hodorowicz-Zaniewska D., Sztefko K. Composition and concentration of serum fatty acids of phospholipids depend on tumor location and disease progression colorectal patients. J. Med. Biochem, 2018, Vol. 37, pp. 1–9.

26. Fernandez-Banares F., Esteve M, et al. Changes of the mucosal n3 andn6 fatty acid status occur early in the colorectal adenoma-carcinoma sequence. Gut. 1996, Vol. 38, no. 2, pp. 254–259.

27. Jones R., Adel-Alvarez L.-A., Alvarez O. R., Broaddus R., Das S. Arachidonic acid and colorectal carcinogenesis. Mol. Cell Biochem. 2003, Vol. 253, N1–2, pp. 141–149.

28. Chapkin R. S., Davidson L. A., Ly L., Weeks B. R., Lupton J. R., Mc Murray D. N. Immunomodulatory effects of (n-3) fatty acids: putative link to infl ammation and colon cancer. J. Nutr. 2007, Vol. 137, no. 1, pp. 200S-204S.

29. Yuksel M., Ates I., Kaplan M., Fettah A. M., et al. Is oxidative stress associated with activation and pathogenesis of inflammatory bowel disease?. J. Med. Biochem. 2017, Vol. 36, pp. 45–49.