Advances in Molecular OncologyAdvances in Molecular OncologyУспехи молекулярной онкологии2313-805X2413-3787Publishing House ABV Press14810.17650/2313-805X-2018-5-2-50-61RESEARCH ARTICLESЭКСПЕРИМЕНТАЛЬНЫЕ СТАТЬИSTUDY OF THE LEVEL OF FATTY ACIDS IN ERYTHROCYTE MEMBRANES AND SERUM OF PATIENTS WITH COLORECTAL CANCER IN NOVOSIBIRSKИССЛЕДОВАНИЕ УРОВНЯ ЖИРНЫХ КИСЛОТ МЕМБРАН ЭРИТРОЦИТОВ И СЫВОРОТКИ КРОВИ У ПАЦИЕНТОВ С КОЛОРЕКТАЛЬНЫМ РАКОМ Г. НОВОСИБИРСКАhttps://orcid.org/0000-0003-0077-3823KruchininaM. V.КручининаМ. В.
Russian Federation

175/1 B. Bogatkova St., Novosibirsk 630089; 52 Krasniy Prospekt, Novosibirsk 630091

Маргарита Витальевна Кручинина.

630089 Новосибирск, ул. Б. Богаткова, 175/1; 630091 Новосибирск, Красный проспект, 52

kruchmargo@yandex.ruhttps://orcid.org/0000-0002-9905-9031KruchininV. N.КручининВ. Н.
Russian Federation

12 Acad. Lavrentieva Prospekt, Novosibirsk 630090

630090 Новосибирск,  проспект акад. Лаврентьева, 13

PrudnikovaYa. I.ПрудниковаЯ. И.
Russian Federation

175/1 B. Bogatkova St., Novosibirsk 630089

630089 Новосибирск, ул. Б. Богаткова, 175/1

GromovA. A.ГромовА. А.
Russian Federation

175/1 B. Bogatkova St., Novosibirsk 630089

630089 Новосибирск, ул. Б. Богаткова, 175/1

https://orcid.org/0000-0002-2688-8410ShashkovM. V.ШашковМ. В.
Russian Federation

5 Acad. Lavrent’eva Prospekt, Novosibirsk 630090

630090 Новосибирск, проспект акад. Лаврентьева, 5

https://orcid.org/0000-0001-5227-9996SokolovaA. S.СоколоваА. С.
Russian Federation

9 Acad. Lavrent’eva Prospekt, Novosibirsk 630090 

630090 Новосибирск, проспект акад. Лаврентьева, 9

Research Institute of Therapy and Preventive Medicine – a branch of the Federal Research Center Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of SciencesНаучно-исследовательский институт терапии и профилактической медицины – филиал ФГБНУ Федеральный исследовательский центр Институт цитологии и генетики СО РАНNovosibirsk State Medical University, Ministry of Health of RussiaФГБОУ ВО «Новосибирский государственный медицинский университет» Минздрава РоссииA.V. Rzhanov Institute of Semiconductor Physics of the Siberian Branch of the Russian Academy of SciencesФГБУН Институт физики полупроводников им. А.В. Ржанова СО РАНG.K. Boreskov Institute of Catalysis of the Siberian Branch of the Russian Academy of SciencesФГБУН Институт катализа им. Г.К. Борескова СО РАНN.N. Vorozhtsov Novosibirsk Institute of Organic ChemistryФГБУН Новосибирский институт органической химии им. Н.Н. Ворожцова СО РАН150520185250611807201818072018Copyright ©; 2018, Kruchinina M.V., Kruchinin V.N., Prudnikova Y.I., Gromov A.A., Shashkov M.V., Sokolova A.S.Copyright ©; 2018, Кручинина М.В., Кручинин В.Н., Прудникова Я.И., Громов А.А., Шашков М.В., Соколова А.С.2018Kruchinina M.V., Kruchinin V.N., Prudnikova Y.I., Gromov A.A., Shashkov M.V., Sokolova A.S.Кручинина М.В., Кручинин В.Н., Прудникова Я.И., Громов А.А., Шашков М.В., Соколова А.С.https://creativecommons.org/licenses/by/4.0https://umo.abvpress.ru/jour/article/view/148

The objective is to measure the level of fatty acids in erythrocyte membranes and serum of patients with colorectal cancer.

Materials and methods. The study group included 100 patients with diagnosed colorectal cancer (57 men and 43 women). The control group included 24 reasonably healthy people (14 men and 10 women) matched for age and sex, without malignant cancers or manifested pathology of the internal organs.

Results. Decreased levels of saturated, monounsaturated fatty acids and increased levels of polyunsaturated fatty acids (PUFAs) in erythrocyte membranes and serum (p <0.0001–0.05) were observed. The levels of omega-3 PUFAs in colorectal cancer exceeded the levels in healthy individuals both in erythrocyte membranes and in serum; for omega-6 PUFAs only a trend was observed. At the same time, the ratio of omega-6/omega-3 PUFAs in colorectal cancer was lower than in control (p <0.0001–0.002). The state of erythrocyte membranes more significantly and for more parameters characterized differences between the groups than serum. The most discriminating parameters between patients with colorectal cancer and healthy individuals both in erythrocyte membranes and serum were the levels of C20:2;11,14 (eicosadienoic), C20:3;8,11,14 (dihomo-γ-linolenic), C20:4;5,8,11,14 (eicosatetraenoic, arachidonic), C22:5;7,10,13,16,19 (docosapentaenoic), and C22:6;4,7,10,13,16,19 (docosahexaenoic) PUFAs.

membrane fatty acidspolyunsaturated fatty acidsserumerythrocytescolorectal cancerжирные кислоты мембранполиненасыщенные жирные кислотысыворотка кровиэритроцитыколоректальный рак1. Brandao D., Ribeiro L. Dietary fatty acids modulation of human colon cancer cells: mechanisms and future perspectives. Int J Food Sci Nutr 2018;69(4):437–50. DOI: 10.1080/09637486.2017.1382456. PMID: 28984495.Brandao D., Ribeiro L. Dietary fatty acids modulation of human colon cancer cells: mechanisms and future perspectives. Int J Food Sci Nutr 2018;69(4):437–50. DOI: 10.1080/09637486.2017.1382456. PMID: 28984495.2. Jia H. J., Zhang P. J., Liu Y. L. et al. Relationship of serum polyunsaturated fatty acids with cytokines in colorectal cancer. World J Gastroenterol 2016;22(8):2524–32. DOI: 10.3748/wjg.v22.i8.2524. PMID: 26937140.Jia H. J., Zhang P. J., Liu Y. L. et al. Relationship of serum polyunsaturated fatty acids with cytokines in colorectal cancer. World J Gastroenterol 2016;22(8):2524–32. DOI: 10.3748/wjg.v22.i8.2524. PMID: 26937140.3. May-Wilson S., Sud A., Law P. J. et al. Pro-inflammatory fatty acid profile and colorectal cancer risk: a Mendelian randomisation analysis. Eur J Cancer 2017;84:228–38. DOI: 10.1016/j.ejca.2017.07.034. PMID: 28829991.May-Wilson S., Sud A., Law P. J. et al. Pro-inflammatory fatty acid profile and colorectal cancer risk: a Mendelian randomisation analysis. Eur J Cancer 2017;84:228–38. DOI: 10.1016/j.ejca.2017.07.034. PMID: 28829991.4. Arab L., Akbar J. Biomarkers and the measurement of fatty acids. Public Health Nutr 2002;5(6A):865–71. PMID: 12638594.Arab L., Akbar J. Biomarkers and the measurement of fatty acids. Public Health Nutr 2002;5(6A):865–71. PMID: 12638594.5. Zeleniuch-Jacquotte A., Chajes V., Van Kappel A. L. et al. Reliability of fatty acid composition in human serum phospholipids. Eur J Clin Nutr 2000;54(5):367–72. PMID: 10822282.Zeleniuch-Jacquotte A., Chajes V., Van Kappel A. L. et al. Reliability of fatty acid composition in human serum phospholipids. Eur J Clin Nutr 2000;54(5):367–72. PMID: 10822282.6. Katan M. B., van Birgelen A., Deslypere J. P. et al. Biological markers of dietary intake, with emphasis on fatty acids. Ann Nutr Metab 1991;35(5):249–52. DOI: 10.1159/000177653. PMID: 1776820.Katan M. B., van Birgelen A., Deslypere J. P. et al. Biological markers of dietary intake, with emphasis on fatty acids. Ann Nutr Metab 1991;35(5):249–52. DOI: 10.1159/000177653. PMID: 1776820.7. Cottet V., Vaysse C., Scherrer M. L. et al. Fatty acid composition of adipose tissue and colorectal cancer: a case-control study. American J Clin Nutr 2015;101(1): 192–201. DOI: 10.3945/ajcn.114.088948. PMID: 25527763.Cottet V., Vaysse C., Scherrer M. L. et al. Fatty acid composition of adipose tissue and colorectal cancer: a case-control study. American J Clin Nutr 2015;101(1): 192–201. DOI: 10.3945/ajcn.114.088948. PMID: 25527763.8. Michalak A., Mosinska P., Fichna J. Polyunsaturated fatty acids and their derivatives: therapeutic value for inflammatory, functional gastrointestinal disorders, and colorectal cancer. Front Pharmacol 2016;7:459–67. DOI: 10.3389/fphar.2016.00459. PMID: 27990120.Michalak A., Mosinska P., Fichna J. Polyunsaturated fatty acids and their derivatives: therapeutic value for inflammatory, functional gastrointestinal disorders, and colorectal cancer. Front Pharmacol 2016;7:459–67. DOI: 10.3389/fphar.2016.00459. PMID: 27990120.9. Mika A., Kobiela J., Czumaj A. et al. Hyper-elongation in colorectal cancer tissue – cerotic acid is a potential novel serum metabolic marker of colorectal malignancies. Cell Physiol Biochem 2017;41(2):722–30. DOI: 10.1159/000458431. PMID: 28214830.Mika A., Kobiela J., Czumaj A. et al. Hyper-elongation in colorectal cancer tissue – cerotic acid is a potential novel serum metabolic marker of colorectal malignancies. Cell Physiol Biochem 2017;41(2):722–30. DOI: 10.1159/000458431. PMID: 28214830.10. Rifkin S. B., Shrubsole M. J., Cai Q. et al. PUFA levels in erythrocyte membrane phospholipids are differentially associated with colorectal adenoma risk. British J Nutr 2017;117(11):1615–22. DOI: 10.1017/S0007114517001490. PMID: 28660850.Rifkin S. B., Shrubsole M. J., Cai Q. et al. PUFA levels in erythrocyte membrane phospholipids are differentially associated with colorectal adenoma risk. British J Nutr 2017;117(11):1615–22. DOI: 10.1017/S0007114517001490. PMID: 28660850.11. 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 2016;408(23):6321–8. DOI: 10.1007/s00216-016-9743-1. PMID: 27379390.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 2016;408(23):6321–8. DOI: 10.1007/s00216-016-9743-1. PMID: 27379390.12. Ogura T., Takada H., Okuno M. et al. Fatty acid composition of plasma, erythrocytes and adipose: their correlations and effects of age and sex. Lipids 2010;45(2):137–44. DOI: 10.1007/s11745-010-3386-3. PMID: 20094809.Ogura T., Takada H., Okuno M. et al. Fatty acid composition of plasma, erythrocytes and adipose: their correlations and effects of age and sex. Lipids 2010;45(2):137–44. DOI: 10.1007/s11745-010-3386-3. PMID: 20094809.13. Bentley D. J., Ackerman J., Clifford T., Slattery K. S. Acute and chronic effects of antioxidant supplementation on exercise performance. In: Antioxidants in sport nutrition. Ed. M. Lamprecht. Boca Raton, Finland, 2015. P. 125.Bentley D. J., Ackerman J., Clifford T., Slattery K. S. Acute and chronic effects of antioxidant supplementation on exercise performance. In: Antioxidants in sport nutrition. Ed. M. Lamprecht. Boca Raton, Finland, 2015. P. 125.14. Ghuman S., Van Hemelrijck M., Garmo H. et al. Serum inflammatory markers and colorectal cancer risk and survival. Br J Cancer 2017;116(10):1358–65. DOI: 10.1038/bjc.2017.96. PMID: 28376082.Ghuman S., Van Hemelrijck M., Garmo H. et al. Serum inflammatory markers and colorectal cancer risk and survival. Br J Cancer 2017;116(10):1358–65. DOI: 10.1038/bjc.2017.96. PMID: 28376082.15. Han S., Schroeder E. A., Silva-Garcia C. G. et al. Monounsaturated fatty acids link H3K4me3 modifiers to C. elegans lifespan. Nature 2017;544(7649):185–90. DOI: 10.1038/nature21686. PMID: 28379943.Han S., Schroeder E. A., Silva-Garcia C. G. et al. Monounsaturated fatty acids link H3K4me3 modifiers to C. elegans lifespan. Nature 2017;544(7649):185–90. DOI: 10.1038/nature21686. PMID: 28379943.16. Shashkov M. V., Sidelnikov V. N. Properties of columns with several pyridinium and imidazolium ionic liquid stationary phases. J Chromatogr A 2013;1309:56–63. DOI: 10.1016/j.chroma.2013.08.030. PMID: 23958690.Shashkov M. V., Sidelnikov V. N. Properties of columns with several pyridinium and imidazolium ionic liquid stationary phases. J Chromatogr A 2013;1309:56–63. DOI: 10.1016/j.chroma.2013.08.030. PMID: 23958690.17. Kang J. X., Wang J. A simplified method for analysis of polyunsaturated fatty acids. BMC Biochem 2005;6:5–13. DOI: 10.1186/1471-2091-6-5. PMID: 15790399.Kang J. X., Wang J. A simplified method for analysis of polyunsaturated fatty acids. BMC Biochem 2005;6:5–13. DOI: 10.1186/1471-2091-6-5. PMID: 15790399.18. Vetvik K. K., Sonerud T., Lindeberg M. et al. Globular adiponectin and its downstream target genes are up-regulated locally in human colorectal tumors: ex vivo and in vitro studies. Metabolism 2014;63(5):672–81. DOI: 10.1016/j.metabol.2014.02.001. PMID: 24636346.Vetvik K. K., Sonerud T., Lindeberg M. et al. Globular adiponectin and its downstream target genes are up-regulated locally in human colorectal tumors: ex vivo and in vitro studies. Metabolism 2014;63(5):672–81. DOI: 10.1016/j.metabol.2014.02.001. PMID: 24636346.19. Zhang P., Wen X., Gu F. et al. Role of serum polyunsaturated fatty acids in the development of colorectal cancer. Int J Clin Exp Med 2015;8(9):15900–9. PMID: 26629093.Zhang P., Wen X., Gu F. et al. Role of serum polyunsaturated fatty acids in the development of colorectal cancer. Int J Clin Exp Med 2015;8(9):15900–9. PMID: 26629093.20. Demignot S., Beilstein F., Morel E. Triglyceride-rich lipoproteins and cytosolic lipid droplets in enterocytes: key players in intestinal physiology and metabolic disorders. Biochimie 2014;96:48–55. DOI: 10.1016/j.biochi.2013.07.009. PMID: 23871915.Demignot S., Beilstein F., Morel E. Triglyceride-rich lipoproteins and cytosolic lipid droplets in enterocytes: key players in intestinal physiology and metabolic disorders. Biochimie 2014;96:48–55. DOI: 10.1016/j.biochi.2013.07.009. PMID: 23871915.21. Agnihotri N., Sharma G., Rani I. et al. Fish oil prevents colon cancer by modulation of structure and function of mitochondria. Biomed Pharmacother 2016;82:90–7. DOI: 10.1016/j.biopha.2016.04.045. PMID: 27470343.Agnihotri N., Sharma G., Rani I. et al. Fish oil prevents colon cancer by modulation of structure and function of mitochondria. Biomed Pharmacother 2016;82:90–7. DOI: 10.1016/j.biopha.2016.04.045. PMID: 27470343.22. Ohmori H., Fujii K., Kadochi Y. et al. Elaidic acid, a trans-fatty acid, enhances the metastasis of colorectal cancer cells. Pathobiology 2017;84(3):144–51. DOI: 10.1159/000449205. PMID: 27832659.Ohmori H., Fujii K., Kadochi Y. et al. Elaidic acid, a trans-fatty acid, enhances the metastasis of colorectal cancer cells. Pathobiology 2017;84(3):144–51. DOI: 10.1159/000449205. PMID: 27832659.23. Katkoori V. R., Manne U., Chaturvedi L. S. et al. Functional consequence of the p53 codon 72 polymorphism in colorectal cancer. Oncotarget 2017;8(44):76574–86. DOI: 10.18632/oncotarget.20580. PMID: 29100333.Katkoori V. R., Manne U., Chaturvedi L. S. et al. Functional consequence of the p53 codon 72 polymorphism in colorectal cancer. Oncotarget 2017;8(44):76574–86. DOI: 10.18632/oncotarget.20580. PMID: 29100333.24. Bozek K., Khrameeva E. E., Reznick J. et al. Lipidome determinants of maximal lifespan in mammals. Sci Rep 2017;7(1):5–17. DOI: 10.1038/s41598-017-00037-7. PMID: 28127055.Bozek K., Khrameeva E. E., Reznick J. et al. Lipidome determinants of maximal lifespan in mammals. Sci Rep 2017;7(1):5–17. DOI: 10.1038/s41598-017-00037-7. PMID: 28127055.25. Fretts A. M., Mozaffarian D., Siscovick D. S. et al. Associations of plasma phospholipid SFAs with total and cause-specific mortality in older adults differ according to SFA chain length. J Nutr 2016;146(2):298–305. DOI: 10.3945/jn.115.222117. PMID: 26701797.Fretts A. M., Mozaffarian D., Siscovick D. S. et al. Associations of plasma phospholipid SFAs with total and cause-specific mortality in older adults differ according to SFA chain length. J Nutr 2016;146(2):298–305. DOI: 10.3945/jn.115.222117. PMID: 26701797.26. Yang Q., Wang S., Ji Y. et al. Dietary intake of n-3 PUFAs modifies the absorption, distribution and bioavailability of fatty acids in the mouse gastrointestinal tract. Lipids Health Dis 2017;16(1):10–21. DOI: 10.1186/s12944-016-0399-9. PMID: 28095863.Yang Q., Wang S., Ji Y. et al. Dietary intake of n-3 PUFAs modifies the absorption, distribution and bioavailability of fatty acids in the mouse gastrointestinal tract. Lipids Health Dis 2017;16(1):10–21. DOI: 10.1186/s12944-016-0399-9. PMID: 28095863.27. Igal R. A. Stearoyl CoA desaturase-1: new insights into a central regulator of cancer metabolism. Biochim Biophys Acta 2016;1861(12 Pt A):1865–80. DOI: 10.1016/j.bbalip.2016.09.009. PMID: 27639967.Igal R. A. Stearoyl CoA desaturase-1: new insights into a central regulator of cancer metabolism. Biochim Biophys Acta 2016;1861(12 Pt A):1865–80. DOI: 10.1016/j.bbalip.2016.09.009. PMID: 27639967.28. Fazio C., Piazzi G., Vitaglione P. et al. Inflammation increases NOTCH1 activity via MMP9 and is counteracted by Eicosapentaenoic Acid-free fatty acid in colon cancer cells. Sci Rep 2016;6: 20670–9. DOI: 10.1038/srep20670. PMID: 26864323.Fazio C., Piazzi G., Vitaglione P. et al. Inflammation increases NOTCH1 activity via MMP9 and is counteracted by Eicosapentaenoic Acid-free fatty acid in colon cancer cells. Sci Rep 2016;6: 20670–9. DOI: 10.1038/srep20670. PMID: 26864323.29. Kato I., Vasquez A., Moyerbrailean G. et al. Nutritional correlates of human oral microbiome. J Am Coll Nutr 2017;36(2):88–98. DOI: 10.1080/07315724.2016.1185386. PMID: 27797671.Kato I., Vasquez A., Moyerbrailean G. et al. Nutritional correlates of human oral microbiome. J Am Coll Nutr 2017;36(2):88–98. DOI: 10.1080/07315724.2016.1185386. PMID: 27797671.30. Kraja B., Muka T., Ruiter R. et al. Dietary fiber intake modifies the positive association between n-3 PUFA intake and colorectal cancer risk in a caucasian population. J Nutr 2015;145(8):1709–16. DOI: 10.3945/jn.114.208462. PMID: 26041678.Kraja B., Muka T., Ruiter R. et al. Dietary fiber intake modifies the positive association between n-3 PUFA intake and colorectal cancer risk in a caucasian population. J Nutr 2015;145(8):1709–16. DOI: 10.3945/jn.114.208462. PMID: 26041678.31. Xia H., Ma S., Wang S., Sun G. Metaanalysis of saturated fatty acid intake and breast cancer risk. Medicine 2015;94(52):e2391–8. DOI: 10.1097/MD.0000000000002391. PMID: 26717389.Xia H., Ma S., Wang S., Sun G. Metaanalysis of saturated fatty acid intake and breast cancer risk. Medicine 2015;94(52):e2391–8. DOI: 10.1097/MD.0000000000002391. PMID: 26717389.32. Angerer T. B., Magnusson Y., Landberg G., Fletcher J. S. Lipid heterogeneity resulting from fatty acid processing in the human breast cancer microenvironment identified by GCIB-ToF-SIMS Imaging. Anal Chem 2016;88(23):11946–54. DOI: 10.1021/acs.analchem.6b03884. PMID: 27783898.Angerer T. B., Magnusson Y., Landberg G., Fletcher J. S. Lipid heterogeneity resulting from fatty acid processing in the human breast cancer microenvironment identified by GCIB-ToF-SIMS Imaging. Anal Chem 2016;88(23):11946–54. DOI: 10.1021/acs.analchem.6b03884. PMID: 27783898.33. Cruz-Gil S., Sanchez-Martinez R., Gomez de Cedron M. et al. Targeting the lipid metabolic axis ACSL/SCD in colorectal cancer progression by therapeutic miRNAs: miR-19b-1 role. J Lipid Res 2018;59(1):14–24. DOI: 10.1194/jlr.M076752. PMID: 29074607.Cruz-Gil S., Sanchez-Martinez R., Gomez de Cedron M. et al. Targeting the lipid metabolic axis ACSL/SCD in colorectal cancer progression by therapeutic miRNAs: miR-19b-1 role. J Lipid Res 2018;59(1):14–24. DOI: 10.1194/jlr.M076752. PMID: 29074607.34. Doria M. L., Ribeiro A. S., Wang J. et al. Fatty acid and phospholipid biosynthetic pathways are regulated throughout mammary epithelial cell differentiation and correlate to breast cancer survival. FASEB J 2014;28(10):4247–64. DOI: 10.1096/fj.14–249672. PMID: 24970396.Doria M. L., Ribeiro A. S., Wang J. et al. Fatty acid and phospholipid biosynthetic pathways are regulated throughout mammary epithelial cell differentiation and correlate to breast cancer survival. FASEB J 2014;28(10):4247–64. DOI: 10.1096/fj.14–249672. PMID: 24970396.35. Shaikh S., Channa N. A., Talpur F. N. et al. Radiotherapy improves serum fatty acids and lipid profile in breast cancer. Lipids Health Dis 2017;16(1):92–9. DOI: 10.1186/s12944-017-0481-y. PMID: 28521812.Shaikh S., Channa N. A., Talpur F. N. et al. Radiotherapy improves serum fatty acids and lipid profile in breast cancer. Lipids Health Dis 2017;16(1):92–9. DOI: 10.1186/s12944-017-0481-y. PMID: 28521812.36. Zhao J., Zhi Z., Wang C. et al. Exogenous lipids promote the growth of breast cancer cells via CD36. Oncol Rep 2017;38(4):2105–15. DOI: 10.3892/or.2017.5864. PMID: 28765876.Zhao J., Zhi Z., Wang C. et al. Exogenous lipids promote the growth of breast cancer cells via CD36. Oncol Rep 2017;38(4):2105–15. DOI: 10.3892/or.2017.5864. PMID: 28765876.37. Gradilla A. C., Sanchez-Hernandez D., Brunt S., Scholpp L. From top to bottom:cell polarity in Hedgehog and Wnt trafficking. BMC Biol 2018;16(1):37–46. DOI: 10.1186/s12915-018-0511-x. PMID: 29636056.Gradilla A. C., Sanchez-Hernandez D., Brunt S., Scholpp L. From top to bottom:cell polarity in Hedgehog and Wnt trafficking. BMC Biol 2018;16(1):37–46. DOI: 10.1186/s12915-018-0511-x. PMID: 29636056.38. Stillwell W. An introduction to biological membtanes. Composition, structure and function. 2nd edn. UK: Elsevier, 2016.Stillwell W. An introduction to biological membtanes. Composition, structure and function. 2nd edn. UK: Elsevier, 2016.39. Rombouts K., Carloni V., Mello T. et al. Myristoylated Alanine-Rich protein Kinase C Substrate (MARCKS) expression modulates the metastatic phenotype in human and murine colon carcinoma in vitro and in vivo. Cancer Lett 2013;333(2):244–52. DOI: 10.1016/j.canlet.2013.01.040. PMID: 23376641.Rombouts K., Carloni V., Mello T. et al. Myristoylated Alanine-Rich protein Kinase C Substrate (MARCKS) expression modulates the metastatic phenotype in human and murine colon carcinoma in vitro and in vivo. Cancer Lett 2013;333(2):244–52. DOI: 10.1016/j.canlet.2013.01.040. PMID: 23376641.40. Sancier F., Dumont A., Sirvent A. et al. Specific oncogenic activity of the srcfamily tyrosine kinase c-Yes in colon carcinoma cells. PLoS One 2011;6(2): e17237–44. DOI: 10.1371/journal.pone.0017237. PMID: 21390316.Sancier F., Dumont A., Sirvent A. et al. Specific oncogenic activity of the srcfamily tyrosine kinase c-Yes in colon carcinoma cells. PLoS One 2011;6(2): e17237–44. DOI: 10.1371/journal.pone.0017237. PMID: 21390316.41. Tae C. H., Kim S. E., Jung S. A. et al. Involvement of adiponectin in early stage of colorectal carcinogenesis. BMC Cancer 2014;14:811–9. DOI: 10.1186/1471-2407-14-811. PMID: 25370174.Tae C. H., Kim S. E., Jung S. A. et al. Involvement of adiponectin in early stage of colorectal carcinogenesis. BMC Cancer 2014;14:811–9. DOI: 10.1186/1471-2407-14-811. PMID: 25370174.42. Habermann N., Schon A., Lund E. K., Glei M. Fish fatty acids alter markers of apoptosis in colorectal adenoma and adenocarcinoma cell lines but fish consumption has no impact on apoptosisinduction ex vivo. Apoptosis 2010;15(5):621–30. DOI: 10.1007/s10495-010-0459-y. PMID: 20107900.Habermann N., Schon A., Lund E. K., Glei M. Fish fatty acids alter markers of apoptosis in colorectal adenoma and adenocarcinoma cell lines but fish consumption has no impact on apoptosisinduction ex vivo. Apoptosis 2010;15(5):621–30. DOI: 10.1007/s10495-010-0459-y. PMID: 20107900.43. Lee J. Y., Sim T. B., Lee J..E, Na H. K. Chemopreventive and chemotherapeutic effects of fish oil derived omega-3 polyunsaturated fatty acids on colon carcinogenesis. Clin Nut Res 2017;6(3):147–60. DOI: 10.7762/cnr.2017.6.3.147. PMID: 28770178.Lee J. Y., Sim T. B., Lee J..E, Na H. K. Chemopreventive and chemotherapeutic effects of fish oil derived omega-3 polyunsaturated fatty acids on colon carcinogenesis. Clin Nut Res 2017;6(3):147–60. DOI: 10.7762/cnr.2017.6.3.147. PMID: 28770178.44. Tuncer S., Banerjee S. Eicosanoid pathway in colorectal cancer: recent updates. World J Gastroenterol 2015;21(41):11748–66. DOI: 10.3748/wjg.v21.i41.11748. PMID: 26557000.Tuncer S., Banerjee S. Eicosanoid pathway in colorectal cancer: recent updates. World J Gastroenterol 2015;21(41):11748–66. DOI: 10.3748/wjg.v21.i41.11748. PMID: 26557000.45. Dupertuis Y. M., Meguid M. M., Pichard C. Colon cancer therapy: new perspectives of nutritional manipulations using polyunsaturated fatty acids. Curr Opin Clin Nutr Metab Care 2007;10(4):427–32. DOI: 10.1097/MCO.0b013e3281e2c9d4. PMID: 17563460.Dupertuis Y. M., Meguid M. M., Pichard C. Colon cancer therapy: new perspectives of nutritional manipulations using polyunsaturated fatty acids. Curr Opin Clin Nutr Metab Care 2007;10(4):427–32. DOI: 10.1097/MCO.0b013e3281e2c9d4. PMID: 17563460.46. Vasudevan A., Yu Y., Banerjee S. et al. Omega-3 fatty acid is a potential preventive agent for recurrent colon cancer. Cancer Prev Res 2014;7(11):1138–48. DOI: 10.1158/1940-6207.CAPR-14-0177. PMID: 25193342.Vasudevan A., Yu Y., Banerjee S. et al. Omega-3 fatty acid is a potential preventive agent for recurrent colon cancer. Cancer Prev Res 2014;7(11):1138–48. DOI: 10.1158/1940-6207.CAPR-14-0177. PMID: 25193342.47. Lim K., Han C., Dai Y. et al. Omega-3 polyunsaturated fatty acids inhibit hepatocellular carcinoma cell growth through blocking beta-catenin and cyclooxygenase-2. Mol Cancer Ther 2009;8(11):3046–55. DOI: 10.1158/1535-7163.MCT-09-0551. PMID: 19887546.Lim K., Han C., Dai Y. et al. Omega-3 polyunsaturated fatty acids inhibit hepatocellular carcinoma cell growth through blocking beta-catenin and cyclooxygenase-2. Mol Cancer Ther 2009;8(11):3046–55. DOI: 10.1158/1535-7163.MCT-09-0551. PMID: 19887546.48. Ma C. J., Wu J. M., Tsai H. L. et al. Prospective double-blind randomized study on the efficacy and safety of an n-3 fatty acid enriched intravenous fat emulsion in postsurgical gastric and colorectal cancer patients. Nutr J 2015;14:9–14 DOI: 10.1186/1475-2891-14-9. PMID: 25609264.Ma C. J., Wu J. M., Tsai H. L. et al. Prospective double-blind randomized study on the efficacy and safety of an n-3 fatty acid enriched intravenous fat emulsion in postsurgical gastric and colorectal cancer patients. Nutr J 2015;14:9–14 DOI: 10.1186/1475-2891-14-9. PMID: 25609264.49. Kim J., Oh S. W., Kim Y. S. et al. Association between dietary fat intake and colorectal adenoma in korean adults: a cross-sectional study. Medicine 2017;96(1):e5759–66. DOI: 10.1097/MD.0000000000005759. PMID: 28072719.Kim J., Oh S. W., Kim Y. S. et al. Association between dietary fat intake and colorectal adenoma in korean adults: a cross-sectional study. Medicine 2017;96(1):e5759–66. DOI: 10.1097/MD.0000000000005759. PMID: 28072719.50. Miccadei S., Masella R., Mileo A. M., Gessani S. Omega-3 polyunsaturated fatty acids as immunomodulators in colorectal cancer: new potential role in adjuvant therapies. Front Immunol 2016;7:486–97. DOI: 10.3389/fimmu.2016.00486. PMID: 27895640. 51.Miccadei S., Masella R., Mileo A. M., Gessani S. Omega-3 polyunsaturated fatty acids as immunomodulators in colorectal cancer: new potential role in adjuvant therapies. Front Immunol 2016;7:486–97. DOI: 10.3389/fimmu.2016.00486. PMID: 27895640. 51.51. Wiese D. M., Horst S. N., Brown C. T. et al. Serum fatty acids are correlated with inflammatory cytokines in ulcerative colitis. PLoS One 2016;11(5):e0156387–94. DOI: 10.1371/journal.pone.0156387. PMID: 27227540.Wiese D. M., Horst S. N., Brown C. T. et al. Serum fatty acids are correlated with inflammatory cytokines in ulcerative colitis. PLoS One 2016;11(5):e0156387–94. DOI: 10.1371/journal.pone.0156387. PMID: 27227540.