BACKGROUND Abnormal metabolism of fatty acids (FA) is considered to play a role in human cancers, including esophageal cancer (EC). Nevertheless, there have been only a few studies dealing with the influence of the chemotherapy or radiotherapy on the plasma FA profiles. In this work we compared FA in plasma phosphatidylcholine (PC) of the patients with squamous EC and healthy subjects and investigated changes in the FA spectrum during neoadjuvant chemoradiotherapy (CRT). MATERIAL AND METHODS Forty-two men with squamous EC were compared with age-matched healthy controls. The EC group was subjected to concurrent neoadjuvant CRT. We analyzed FA in plasma PC before and after CRT. RESULTS The EC group was characterized by increased levels of both saturated and monounsaturated FA, associated with an increased index of SCD1 (stearoyl-CoA desaturase-1). Moreover, decreased levels of linoleic acid and total polyunsaturated FA (PUFA) n-6 were found in EC patients. The CRT was accompanied by increased docosahexaenoic acid and total PUFA n-3 content in plasma PC, concurrently with the decrease of estimated activity of SCD1. CONCLUSIONS We found that patients with EC had altered FA profile in plasma PC, which could be related to abnormal FA metabolism in cancer (e.g., altered synthesis de novo, b-oxidation, desaturation, and elongation). The described changes in FA profiles during CRT could be involved in favorable functioning of CRT. Further studies investigating the plasma FA compositions and their changes due to CRT in EC patients are warranted.

4th Department of Internal Medicine 1st Faculty of Medicine of Charles University Prague and General University Hospital Prague Czech Republic

Department of Oncology 1st Faculty of Medicine of Charles University Prague and General University Hospital Prague Czech Republic

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Coleman MP, Gatta G, Verdecchia A, et al. EUROCARE Working Group. EUROCARE-3 summary: Cancer survival in Europe at the end of the 20th century. Ann Oncol. 2003;14(Suppl 5):128–49. PubMed

ÚZIS ČR. Novotvary 2011. Prague: ÚZIS; 2014. [in Czech]

Bravi F, Edefonti V, Randi G, et al. Dietary patterns and the risk of esophageal cancer. Ann Oncol. 2012;23:765–70. PubMed

Pohl H, Wrobel K, Bojarski C, et al. Risk factors in the development of esophageal adenocarcinoma. Am J Gastroenterol. 2013;108:200–7. PubMed

Zemanová M, Staňková B, Ušiakova Z, et al. Serum adiponectin relates to shortened overall survival in men with squamous cell esophageal cancer treated with preoperative concurrent chemoradiotherapy: a pilot study. Med Sci Monit. 2014;20:2351–57. PubMed PMC

Chen H, Tucker KL, Graubard BI, et al. Nutrient intakes and adenocarcinoma of the esophagus and distal stomach. Nutr Cancer. 2002;42:33–40. PubMed

Bahmanyar S, Ye W. Dietary patterns and risk of squamous-cell carcinoma and adenocarcinoma of the esophagus and adenocarcinoma of the gastric cardia: A population-based case-control study in Sweden. Nutr Cancer. 2006;54:171–78. PubMed

Hajizadeh B, Jessri M, Akhoondan M, et al. Nutrient patterns and risk of esophageal squamous cell carcinoma: A case-control study. Dis Esophagus. 2012;25(5):442–48. PubMed

De Stefani E, Deneo-Pellegrini H, Ronco AL, et al. Diet patterns and risk of squamous cell oesophageal carcinoma: a case-control study in Uruguay. Asian Pac J Cancer Prev. 2014;15(6):2765–69. PubMed

Hodson L, Skeaff CM, Fielding BA. Fatty acid composition of adipose tissue and blood in humans and its use as a biomarker of dietary intake. Prog Lipid Res. 2008;47(5):348–80. PubMed

Santos CR, Schulze A. Lipid metabolism in cancer. FEBS J. 2012;279(15):2610–23. PubMed

Das UN. Perinatal supplementation of long-chain polyunsaturated fatty acids, immune response and adult diseases. Med Sci Monit. 2004;10(5):HY19–25. PubMed

Zuijdgeest-van Leeuwen SD, van der Heijden MS, Rietveld T, et al. Fatty acid composition of plasma lipids in patients with pancreatic, lung and oesophageal cancer in comparison with healthy subjects. Clin Nutr. 2002;21(3):225–30. PubMed

Zhang J, Bowers J, Liu L, et al. Esophageal cancer metabolite biomarkers detected by LC-MS and NMR methods. PLoS One. 2012;7(1):e30181. PubMed PMC

Guo S, Wang Y, Zhou D, Li Z. Significantly increased monounsaturated lipids relative to polyunsaturated lipids in six types of cancer microenvironment are observed by mass spectrometry imaging. Sci Rep. 2014;4:5959. PubMed PMC

Rysman E, Brusselmans K, Scheys K, et al. De novo lipogenesis protects cancer cells from free radicals and chemotherapeutics by promoting membrane lipid saturation. Cancer Res. 2010;70(20):8117–26. PubMed

Pratt VC, Watanabe S, Bruera E, et al. Plasma and neutrophil fatty acid composition in advanced cancer patients and response to fish oil supplementation. Br J Cancer. 2002;87(12):1370–78. PubMed PMC

McClinton S, Moffat LE, Horrobin DF, et al. Abnormalities of essential fatty acid distribution in the plasma phospholipids of patients with bladder cancer. Br J Cancer. 1991;63(2):314–16. PubMed PMC

Cvetković Z, Vucić V, Cvetković B, et al. Abnormal fatty acid distribution of the serum phospholipids of patients with non-Hodgkin lymphoma. Ann Hematol. 2010;89(8):775–82. PubMed

Kurabe N, Hayasaka T, Ogawa M, et al. Accumulated phosphatidylcholine (16: 0/16: 1) in human colorectal cancer; Possible involvement of LPCAT4. Cancer Sci. 2013;104(10):1295–302. PubMed PMC

Marien E, Meister M, Muley T, et al. Non-small cell lung cancer is characterized by dramatic changes in phospholipid profiles. Int J Cancer. 2015;137(7):1539–48. PubMed PMC

TNM classification of malignant tumours. fifth edition. Czech version; 2000.

Zemanová M, Petruželka L, Pazdro A, et al. Prospective non-randomized study of preoperative concurrent platinum plus 5-fluorouracil-based chemoradiotherapy with or without paclitaxel in esophageal cancer patients: long-term follow-up. Dis Esophagus. 2010;23(2):160–67. PubMed

Tvrzická E, Vecka M, Staňková B, et al. Analysis of fatty acids in plasma lipoproteins by gas chromatography-flame ionization detection Quantitative aspects. Anal Chim Acta. 2002;465:337–50.

Lupu R, Menendez JA. Targeting fatty acid synthase in breast and endometrial cancer: An alternative to selective estrogen receptor modulators? Endocrinology. 2008;147:4056–66. PubMed

Zhou Y, Niu C, Li Y, et al. Fatty acid synthase expression and esophageal cancer. Mol Biol Rep. 2012;39(10):9733–39. PubMed

Li J, Ding SF, Habib NA, et al. Partial characterization of a cDNA for human stearoyl-CoA desaturase and changes in its mRNA expression in some normal and malignant tissues. Int J Cancer. 1994;57:348–52. PubMed

Macášek J, Vecka M, Žák A, et al. Plasma fatty acid composition in patients with pancreatic cancer: correlations to clinical parameters. Nutr Cancer. 2012;64(7):946–55. PubMed

Scaglia N, Igal RA. Inhibition of Stearoyl-CoA Desaturase 1 expression in human lung adenocarcinoma cells impairs tumorigenesis. Int J Oncol. 2008;33(4):839–50. PubMed

Ma J, Folsom AR, Shahar E, et al. Plasma fatty acid composition as an indicator of habitual dietary fat intake in middle-aged adults. The Atherosclerosis Risk in Communities (ARIC) Study Investigators. Am J Clin Nutr. 1995;62(3):564–71. PubMed

Zock PL, Mensink RP, Harryvan J, et al. Fatty acids in serum cholesteryl esters as quantitative biomarkers of dietary intake in humans. Am J Epidemiol. 1997;145(12):1114–22. PubMed

Simon JA, Fong J, Bernert JT, et al. Relation of smoking and alcohol consumption to serum fatty acids. Am J Epidemiol. 1996;144:325–34. PubMed

Bagnardi V, Rota M, Botteri E, et al. Light alcohol drinking and cancer: A meta-analysis. Ann Oncol. 2013;24(2):301–8. PubMed

Žák A, Jáchymová M, Tvrzická E, et al. The influence of polymorphisms of −493G/T MTP gene promoter and metabolic syndrome on lipids, fatty acids and oxidative stress. J Nutr Biochem. 2008;19:634–41. PubMed

Zeman M, Vecka M, Jáchymová M, et al. Fatty acid CoA ligase-4 gene polymorphism influences fatty acid metabolism in metabolic syndrome, but not in depression. Tohoku J Exp Med. 2009;217:287–93. PubMed

Žák A, Tvrzická E, Vecka M, et al. Severity of metabolic syndrome unfavorably influences oxidative stress and fatty acid metabolism in men. Tohoku J Exp Med. 2007;212:359–71. PubMed

Diakowska D, Lewandowski A, Kopeć W, et al. Oxidative DNA damage and total antioxidant status in serum of patients with esophageal squamous cell carcinoma. Hepatogastroenterology. 2007;54(78):1701–4. PubMed

Murphy RA, Bureyko TF, Mourtzakis M, et al. Aberrations in plasma phospholipid fatty acids in lung cancer patients. Lipids. 2012;47(4):363–69. PubMed

He C, Qu X, Wan J, et al. Inhibiting delta-6 desaturase activity suppresses tumor growth in mice. PLoS One. 2012;7(10):e47567. PubMed PMC

Hansen-Petrik MB, McEntee MF, Johnson BT, et al. Selective inhibition of Delta-6 desaturase impedes intestinal tumorigenesis. Cancer Lett. 2002;175(2):157–63. PubMed

Pender-Cudlip MC, Krag KJ, Martini D, et al. Delta-6-desaturase activity and arachidonic acid synthesis are increased in human breast cancer tissue. Cancer Sci. 2013;104(6):760–64. PubMed PMC

Bougnoux P, Hajjaji N, Ferrasson MN, et al. Improving outcome of chemotherapy of metastatic breast cancer by docosahexaenoic acid: A phase II trial. Br J Cancer. 2009;101(12):1978–85. PubMed PMC

Plourde M, Chouinard-Watkins R, Vandal M, et al. Plasma incorporation, apparent retroconversion and β-oxidation of 13C-docosahexaenoic acid in the elderly. Nutr Metab (Lond) 2011;8:5. PubMed PMC

Plourde M, Vohl MC, Vandal M, et al. Plasma n-3 fatty acid response to an n-3 fatty acid supplement is modulated by apoE epsilon4 but not by the common PPAR-alpha L162V polymorphism in men. Br J Nutr. 2009;102(8):1121–24. PubMed

Raatz SK, Young LR, Picklo MJ, Sr, et al. Total dietary fat and fatty acid content modifies plasma phospholipid fatty acids, desaturase activity indices, and urinary prostaglandin E in women. Nutr Res. 2012;32(1):1–7. PubMed

Garcia JM, Scherer T, Chen JA, et al. Inhibition of cisplatin-induced lipid catabolism and weight loss by ghrelin in male mice. Endocrinology. 2013;154(9):3118–29. PubMed PMC

Das UN, Madhavi N. Effect of polyunsaturated fatty acids on drug-sensitive and resistant tumor cells in vitro. Lipids Health Dis. 2011;10:159. PubMed PMC

Chénais B, Blanckaert V. The janus face of lipids in human breast cancer: How polyunsaturated Fatty acids affect tumor cell hallmarks. Int J Breast Cancer. 2012;2012:712536. PubMed PMC

Hajjaji N, Bougnoux P. Selective sensitization of tumors to chemotherapy by marine-derived lipids: a review. Cancer Treat Rev. 2013;39(5):473–88. PubMed

Serum Metabolite Biomarkers for Pancreatic Tumors: Neuroendocrine and Pancreatic Ductal Adenocarcinomas-A Preliminary Study