Medullary Thyroid Carcinoma - Circulating Status of Vaspin and Retinol Binding Protein-4 in Iranian Patients

  • Jabbari, Sepideh (Department of Biology, Science and Research Branch, Islamic Azad University) ;
  • Hedayati, Mehdi (Cellular and Molecular Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences) ;
  • Yaghmaei, Parichehreh (Department of Biology, Science and Research Branch, Islamic Azad University) ;
  • Parivar, Kazem (Department of Biology, Science and Research Branch, Islamic Azad University)
  • Published : 2015.10.06


Background: Vaspin and Retinol binding protein-4 (RBP4) are new adipokines mainly produced by adipose tissue. Considering that medullary thyroid carcinoma (MTC) is a malignant neuroendocrine tumor, and to date the relationship between serum levels of vaspin and RBP4 with MTC has not been studied, in this matched case-control study we evaluated their possible significance to this tumor type. Materials and Methods: A total of 45 patients with MTC (21 males and 24 females) and 45 healthy persons as a control group (24 males and 21 females) were selected. The two groups were matched for age, sex and body mass index. Serum Vaspin and RBP4 levels were measured by enzyme-linked immunosorbent assay (ELISA) methods in both groups. Also, weight and height were measured and body mass index was calculated too. Results: In total, patients with MTC had significantly higher serum vaspin levels compared to the controls (0.52ng/ml vs. 0.45ng/ml, P=0.0241). However, no significant difference was found in serum RBP4 concentrations between the patients with MTC and the controls ($15.2{\pm}2.55{\mu}g/ml$ versus $15.1{\pm}3.34{\mu}g/ml$, p>0.05). Conclusions: The results of this study demonstrated that serum RBP4 levels in MTC patients are not significantly different from those found in healthy individuals and did not correlate with MTC. On the other hand, higher levels of serum vaspin are associated with an increased risk of MTC. Thus Vaspin may be a novel and promising biomarker for diagnosis or confirmation of MTC in conjunction other specific tumor markers.


Vaspin;retinol binding protein 4;adipokine;medullary;thyroid carcinoma


Supported by : Shahid Beheshti University of Medical Sciences


  1. Abel ED, Peroni O, Kim JK, et al (2001). Adipose-selective targeting of the GLUT4 gene impairs insulin action in muscle and liver. Nature, 409, 729-33.
  2. Abulaizi M, Tomonaga T, Satoh M, et al (2011). The application of a three-step proteome analysis for identification of new biomarkers of pancreatic cancer. Int J Proteomics, 2011, 628787.
  3. Aktas B, Yilmaz Y, Eren F, et al (2011). Serum levels of vaspin, obestatin, and apelin-36 in patients with nonalcoholic fatty liver disease. Metabolism, 60, 544-9.
  4. Alvandi E, Akrami SM, ChianiM, et al (2011). Molecular analysis of the RET proto-oncogene key exons in patients with medullary thyroid carcinoma: a comprehensive study of the Iranian population. Thyroid, 21, 373-82.
  5. Bluher M (2012). Vaspin in obesity and diabetes: pathophysiological and clinical significance. Endocrine, 41, 176-82.
  6. Bluher M (2014). Adipokines-removing road blocks to obesity and diabetes therapy. Mol Metab, 3, 230-40.
  7. Cheng Y, Liu C, Zhang N, et al (2014). Proteomics analysis for finding serum markers of ovarian cancer. Biomed Res Int, 2014, 1-9.
  8. Colantuoni V, Romano V, Bensi G, et al (1983). Cloning and sequencing of a full length cDNA coding for human retinolbinding protein. Nucleic Acids Res, 11, 7769-76.
  9. Duggirala R, Blangero J, Almasy L, et al (1999). Linkage of type 2 diabetes mellitus and of age at onset to a genetic location on chromosome 10q in mexican americans. Am J Hum Genet, 64, 1127-40.
  10. El-Mesallamy HO, Hamdy NM, Zaghloul AS, et al (2013). Clinical value of circulating lipocalins and insulin-like growth factor axis in pancreatic cancer diagnosis. Pancreas, 42, 149-54.
  11. Erdogan S, Sezer S, Baser E, et al (2013). Evaluating vaspin and adiponectin in postmenopausal women with endometrial cancer. Endocr Relat Cancer, 20, 669-75.
  12. Fabris C, Piccoli A, Meani A, et al (1984). Study of retinolbinding protein in pancreatic cancer. J Cancer Res Clin Oncol, 108, 227-9.
  13. Fazeli MS, Dashti H, Akbarzadeh S, et al (2013). Circulating levels of novel adipocytokines in patients with colorectal cancer. Cytokine, 62, 81-5.
  14. Feng R, Li Y, Wang C, et al (2014). Higher vaspin levels in subjects with obesity and type 2 diabetes mellitus: A metaanalysis. Diabetes Res Clin Pract, 106, 88-94.
  15. Flower DR (1996). The lipocalin protein family: structure and function. Biochem J, 318, 1-14.
  16. Ghaemmaghami S, Mohaddes SM, Hedayati M, et al (2013). Resistin and visfatin expression in HCT-116 colorectal cancer cell line. Int J Mol Cell Med, 2, 143-50.
  17. Hedayati M, Nabipour I, Rezaei-Ghaleh N, et al (2006). Germline RET mutations in exons 10 and 11: an Iranian survey of 57 medullary thyroid carcinoma cases. Med J Malaysia, 61, 564-9.
  18. Hedayati M, Yaghmaei P, Pooyamanesh Z, et al (2011). Leptin: a correlated peptide to papillary thyroid carcinoma? J Thyroid Res, 2011, 832163.
  19. Hedayati M, Zarif Yeganeh M, Sheikhol Eslami S, et al (2011). Predominant RET germline mutations in exons 10, 11, and 16 in Iranian patients with hereditary medullary thyroid carcinoma. J Thyroid Res, 2011, 264248.
  20. Hida K, Wada J, Eguchi J, et al (2005). Visceral adipose tissuederived serine protease inhibitor: a unique insulin-sensitizing adipocytokine in obesity. Proc Natl Acad Sci U S A, 102, 10610-15.
  21. Jian W, Peng W, Xiao S, et al (2014). Role of serum vaspin in progression of type 2 diabetes: a 2-year cohort study. PloS one, 9, 94763.
  22. Jung CH, Lee WJ, Hwang JY, et al (2011). Vaspin protects vascular endothelial cells against free fatty acid-induced apoptosis through a phosphatidylinositol 3-kinase/Akt pathway. Biochem Biophys Res Commun, 413, 264-9.
  23. Jung UJ, Choi MS (2014). Obesity and its metabolic complications: the role of adipokines and the relationship between obesity, inflammation, insulin resistance, dyslipidemia and nonalcoholic fatty liver disease. Int J Mol Sci, 15, 6184-223.
  24. Kadoglou NP, Gkontopoulos A, Kapelouzou A, et al (2011). Serum levels of vaspin and visfatin in patients with coronary artery disease-Kozani study. Clin Chim Acta, 412, 48-52.
  25. Kloting N, Berndt J, Kralisch S, et al (2006). Vaspin gene expression in human adipose tissue: association with obesity and type 2 diabetes. Biochem Biophys Res Commun, 339, 430-6.
  26. Kloting N, Kovacs P, Kern M, et al (2011). Central vaspin administration acutely reduces food intake and has sustained blood glucose-lowering effects. Diabetologia, 54, 1819-23.
  27. Kotnik P, Fischer-Posovszky P, Wabitsch M (2011). RBP4: a controversial adipokine. Eur J Endocrinol, 165, 703-11.
  28. Lee JA, Park HS, Song YS, et al (2011). Relationship between vaspin gene expression and abdominal fat distribution of Korean women. Endocr J, 58, 639-46.
  29. Lee YC, Chen YJ, Wu CC, et al (2012). Resistin expression in breast cancer tissue as a marker of prognosis and hormone therapy stratification. Gynecol Oncol, 125, 742-50.
  30. Lorkova L, Pospisilova J, Lacheta J, et al (2012). Decreased concentrations of retinol-binding protein 4 in sera of epithelial ovarian cancer patients: a potential biomarker identified by proteomics. Oncol Rep, 27, 318-24.
  31. Ghazi AA, Bagheri M, Tabibi A, et al (2014). Multiple endocrine neoplasia type 2a in an iranian family: clini-cal and genetic studies. Arch Iran Med, 17, 378-82.
  32. Majidi M, Haghpanah V, Hedayati M, et al (2011). A family presenting with multiple endocrine neoplasia type 2B: A case report. J Med Case Rep, 5, 587.
  33. Meigs JB, Panhuysen CI, Myers RH, et al (2002). A genomewide scan for loci linked to plasma levels of glucose and HbA1c in a community-based sample of caucasian Pedigrees The framingham offspring Study. Diabetes, 51, 833-40.
  34. Mirzaei K, Hossein-nezhad A, Keshavarz SA, et al (2013). Crosstalk between circulating peroxisome proliferatoractivated receptor gamma, adipokines and metabolic syndrome in obese subjects. Diabetol Metab Syndr, 5, 79.
  35. Nair AK, Sugunan D, Kumar H, et al (2010). Case-control analysis of SNPs in GLUT4, RBP4 and STRA6: association of SNPs in STRA6 with type 2 diabetes in a South Indian population. PLoS One, 5, 11444.
  36. Newcomer ME, Ong DE (2000). Plasma retinol binding protein: structure and function of the prototypic lipocalin. Biochim Biophys Acta, 1482, 57-64.
  37. Ouchi N, Parker JL, Lugus JJ, et al (2011). Adipokines in inflammation and metabolic disease. Nat Rev Immunol, 11, 85-97.
  38. Patz EF Jr, Campa MJ, Gottlin EB, et al (2007). Panel of serum biomarkers for the diagnosis of lung cancer. J Clin Oncol, 25, 5578-83.
  39. Phalitakul S, Okada M, Hara Y, et al (2013). Vaspin prevents methylglyoxal-induced apoptosis in human vascular endothelial cells by inhibiting reactive oxygen species generation. Acta Physiologica, 209, 212-9.
  40. Putzki H, Reichert B, Hinz M (1990). Retinol-binding protein, haptoglobin and ceruloplasmin--tumor markers in colorectal cancer? Z Gesamte Inn Med, 45, 50-52.
  41. Saboori S, Hosseinzadeh-Attar MJ, Hosseini M, et al (2013). The comparison of serum vaspin and visfatin concentrations in obese and normal weight women. Diabetes Metab Syndr.
  42. Sahin-Efe A, Katsikeris F, Mantzoros CS (2012). Advances in adipokines. Metabolism, 61, 1659-65.
  43. Sheikholeslami S, Yeganeh MZ, Rad LH, et al (2014). Haplotype Frequency of G691S/S904S in the RET proto-onco-gene in Patients with medullary thyroid carcinoma. Iran J Public Health, 43, 235-40.
  44. Tsunoda S, Smith E, De Young NJ, et al (2009). Methylation of CLDN6, FBN2, RBP1, RBP4, TFPI2, and TMEFF2 in esophageal squamous cell carcinoma. Oncol Rep, 21, 1067-73.
  45. Tsutsumi C, Okuno M, Tannous L, et al (1992). Retinoids and retinoid-binding protein expression in rat adipocytes. J Biol Chem, 267, 1805-10.
  46. Uehara H, Takahashi T, Izumi K (2013). Induction of retinolbinding protein 4 and placenta-specific 8 expression in human prostate cancer cells remaining in bone following osteolytic tumor growth inhibition by osteoprotegerin. Int J Oncol, 43, 365-74.
  47. Wada J (2008). Vaspin: a novel serpin with insulin-sensitizing effects. Expert Opin Investig Drugs, 17, 327-33.
  48. Wang DD, Zhao YM, Wang L, et al (2011). Preoperative serum retinol-binding protein 4 is associated with the prognosis of patients with hepatocellular carcinoma after curative resection. J Cancer Res Clin Oncol, 137, 651-8.
  49. Yeganeh MZ, Sheikholeslami S, Behbahani GD, et al (2015). Skewed mutational spectrum of RET proto-oncogene Exon10 in Iranian patients with medullary thyroid carcinoma.Tumor Biol, [Epub ahead of print].
  50. Zarif-Yeganeh M, Sheikholeslami S, Dehbashi-Behbahani G, et al (2015). Point mutations in ret proto-oncogene exon 10 in Patients with medullary thyroid carcinoma. J Kerman Univ Med Sci, 22, 249-60.
  51. Zhu X, Jiang Y, Shan PF, et al (2013). Vaspin attenuates the apoptosis of human osteoblasts through ERK signaling pathway. Amino Acids, 44, 961-8.

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