Decreased Expression of FADS1 Predicts a Poor Prognosis in Patients with Esophageal Squamous Cell Carcinoma

  • Du, Yong (State Key Laboratory of Oncology in South China, Department of Experimental Research, Sun Yat-sen University Cancer Center) ;
  • Yan, Shu-Mei (Department of Pathology, Sun Yat-sen University Cancer Center) ;
  • Gu, Wan-Yi (Department of Pathology, The Fourth Affiliated Hospital of Guangzhou Medical College, Sun Yat-sen University) ;
  • He, Fan (Department of Forensic Medicine, Zhongshan School of Medicine, Sun Yat-sen University) ;
  • Huang, Li-Yun (Department of Pathology, Sun Yat-sen University Cancer Center) ;
  • Li, Mei (Department of Pathology, Sun Yat-sen University Cancer Center) ;
  • Yuan, Yan (Section 3 of Internal Medicine, The Affiliated Tumor Hospital of Guangzhou Medical University) ;
  • Chen, Ren-Hui (Department of Head and Neck Surgery, The Second Affiliated Hospital, Sun Yat-sen University) ;
  • Zhong, Qian (State Key Laboratory of Oncology in South China, Department of Experimental Research, Sun Yat-sen University Cancer Center) ;
  • Li, Man-Zhi (State Key Laboratory of Oncology in South China, Department of Experimental Research, Sun Yat-sen University Cancer Center) ;
  • Li, Yong (Department of Pathology, Sun Yat-sen University Cancer Center) ;
  • Zeng, Mu-Sheng (State Key Laboratory of Oncology in South China, Department of Experimental Research, Sun Yat-sen University Cancer Center)
  • Published : 2015.07.13


FADS1 (fatty acid desaturase 1) plays a crucial role in fatty acid metabolism, and it was recently reported to be involved in tumorigenesis. However, the role of FADS1 expression in esophageal squamous cell carcinoma (ESCC) remains unknown. In the current study, we investigated the expression and clinical pathologic and prognostic significance of FADS1 in ESCC. Immunohistochemical analyses revealed that 58.2% (146/251) of the ESCC tissues had low levels of FADS1 expression, whereas 41.8% (105/251) exhibited high levels of FADS1 expression. In positive cases, FADS1 expression was detected in the cytoplasm of cells. Correlation analyses demonstrated that FADS1 expression was significantly correlated with tumor location (p=0.025) but not with age, gender, histological grade, tumor status, nodal status or TNM staging. Furthermore, patients with tumors expressing high levels of FADS1had a longer disease-free survival time (p<0.001) and overall survival time (p <0.001). Univariate and multivariate analyses revealed that, along with nodal status, FADS1 expression was an independent and significant predictive factor (p<0.001). In conclusion, our study suggested that FADS1 might be a valuable biomarker and potential therapeutic target for ESCC.


FADS1;Esophageal squamous cell carcinoma;prognosis;survival


  1. Chen SB, Weng HR, Wang G, et al (2013). Surgical treatment for early esophageal squamous cell carcinoma. Asian Pac J Cancer Prev, 14, 3825-30.
  2. Currie E, Schulze A, Zechner R, et al (2013). Cellular fatty acid metabolism and cancer. Cell Metab, 18, 153-61.
  3. Engel LS, Chow WH, Vaughan TL, et al (2003). Population attributable risks of esophageal and gastric cancers. J Natl Cancer Inst, 95, 1404-13.
  4. Eschwege P, de Ledinghen V, Camilli T, et al (2001). Arachidonic acid and prostaglandins, inflammation and oncology. Presse Med, 30, 508-10.
  5. Fan YY, Monk JM, Hou TY, et al (2012). Characterization of an arachidonic acid-deficient (Fads1 knockout) mouse model. J Lipid Res, 53, 1287-95.
  6. Gholipour C, Shalchi RA, Abbasi M (2008). A histopathological study of esophageal cancer on the western side of the Caspian littoral from 1994 to 2003. Dis Esophagus, 21, 322-7.
  7. Glaser C, Lattka E, Rzehak P, et al (2011). Genetic variation in polyunsaturated fatty acid metabolism and its potential relevance for human development and health. Matern Child Nutr, 7, 27-40.
  8. He C, Qu X, Wan J, et al (2012). Inhibiting delta-6 desaturase activity suppresses tumor growth in mice. PLoS One, 7, 47567.
  9. Jemal A, Bray F, Center MM, et al (2011). Global cancer statistics. CA Cancer J Clin, 61, 69-90.
  10. Karin M, Greten FR (2005). NF-kappaB: linking inflammation and immunity to cancer development and progression. Nat Rev Immunol, 5, 749-59.
  11. Kuehl FA, Jr, Egan RW (1980). Prostaglandins, arachidonic acid, and inflammation. Science, 210, 978-84.
  12. Lee CH, Lee JM, Wu DC, et al (2005). Independent and combined effects of alcohol intake, tobacco smoking and betel quid chewing on the risk of esophageal cancer in Taiwan. Int J Cancer, 113, 475-82.
  13. Li CC, Hou YC, Yeh CL, et al (2014). Effects of eicosapentaenoic acid and docosahexaenoic acid on prostate cancer cell migration and invasion induced by tumor-associated macrophages. PLoS One, 9, 99630.
  14. Liu J, Ma DW (2014). The role of n-3 polyunsaturated fatty acids in the prevention and treatment of breast cancer. Nutrients, 6, 5184-223.
  15. Liu Y, Zhu X, Zhu J, et al (2007). Identification of differential expression of genes in hepatocellular carcinoma by suppression subtractive hybridization combined cDNA microarray. Oncol Rep, 18, 943-51.
  16. Marquardt A, Stohr H, White K, et al (2000). cDNA cloning, genomic structure, and chromosomal localization of three members of the human fatty acid desaturase family. Genomics, 66, 175-83.
  17. Mullen A, Loscher CE, Roche HM (2010). Anti-inflammatory effects of EPA and DHA are dependent upon time and dose-response elements associated with LPS stimulation in THP-1-derived macrophages. J Nutr Biochem, 21, 444-50.
  18. Blanchard H, Legrand P, Pedrono F (2011). Fatty acid desaturase 3 (Fads3) is a singular member of the fads cluster. Biochimie, 93, 87-90.
  19. Cairns RA, Harris IS, Mak TW (2011). Regulation of cancer cell metabolism. Nat Rev Cancer, 11, 85-95.
  20. Calder PC (2008). Polyunsaturated fatty acids, inflammatory processes and inflammatory bowel diseases. Mol Nutr Food Res, 52, 885-97.
  21. Carracedo A, Cantley LC, Pandolfi PP (2013). Cancer metabolism: fatty acid oxidation in the limelight. Nat Rev Cancer, 13, 227-32.
  22. Rahman MM, Veigas JM, Williams PJ, et al (2013). DHA is a more potent inhibitor of breast cancer metastasis to bone and related osteolysis than EPA. Breast Cancer Res Treat, 141, 341-52.
  23. Sala-Vila A, Miles EA, Calder PC (2008). Fatty acid composition abnormalities in atopic disease: evidence explored and role in the disease process examined. Clin Exp Allergy, 38, 1432-50.
  24. Song Y, Li L, Ou Y, et al (2014). Identification of genomic alterations in oesophageal squamous cell cancer. Nature, 509, 91-5.
  25. Wang D, Li M, Wei D, et al (2007). Identification and functional characterization of the delta 6-fatty acid desaturase gene from Thamnidium elegans. J Eukaryot Microbiol, 54, 110-7.
  26. Wang L, Athinarayanan S, Jiang G, et al (2015). Fatty acid desaturase 1 (FADS1) gene polymorphisms control human hepatic lipid composition. Hepatology, 61, 119-28.
  27. Wu IC, Lu CY, Kuo FC, et al (2006). Interaction between cigarette, alcohol and betel nut use on esophageal cancer risk in Taiwan. Eur J Clin Invest, 36, 236-41.
  28. Yamashita S, Tsujino Y, Moriguchi K, et al (2006). Chemical genomic screening for methylation-silenced genes in gastric cancer cell lines using 5-aza-2'-deoxycytidine treatment and oligonucleotide microarray. Cancer Sci, 97, 64-71.
  29. Yang P, Jiang Y, Fischer SM (2014). Prostaglandin E3 metabolism and cancer. Cancer Lett, 348, 1-11.
  30. Zhang B, Jia WH, Matsuda K, et al (2014). Large-scale genetic study in East Asians identifies six new loci associated with colorectal cancer risk. Nat Genet, 46, 533-42.

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