Advances in Clinical and Experimental Medicine
2019, vol. 28, nr 5, May, p. 671–678
Publication type: original article
Assessment of apelin, apelin receptor, resistin, and adiponectin levels in the primary tumor and serum of patients with esophageal squamous cell carcinoma
1 Department of Nervous System Diseases, Faculty of Health Science, Wroclaw Medical University, Poland
2 Department of Gastrointestinal and General Surgery, Wroclaw Medical University, Poland
3 Department of Medical Biochemistry, Wroclaw Medical University, Poland
Background. Disturbances in adipokine secretion are associated with the risk of cancer growth and progression.
Objectives. The aim of the study was to evaluate the mRNA expression and protein levels of apelin, the apelin receptor, resistin, and adiponectin in the tumor tissues of surgically treated esophageal squamous cell carcinoma (ESCC) patients. Concentrations of serum adipokines were assessed in relation to ESCC progression.
Material and Methods. The study group consisted of 53 patients with ESCC and 27 controls. In the ESCC group, 27 patients were surgically treated and 26 were treated with palliative procedures. RT-PCR and ELISA tests were used to measure the mRNA expression and protein level of adipokines in tissues and their concentration in serum.
Results. We found that mRNA expression and protein concentrations of apelin, the apelin receptor and resistin were significantly higher in tumor tissue than in control tissue. The protein concentration of apelin were significantly increased in the tumors of patients with lymph node metastasis (p < 0.005). Circulating levels of apelin, the apelin receptor and resistin were significantly higher in the cancer patients than in controls (p < 0.05 for all). The concentration of serum apelin receptor significantly decreased in patients with stage IV cancer, the presence of lymph node or distant metastasis (p < 0.05).
Conclusion. Apelin may participate in lymphangiogenesis and the progression of ESCC. The apelin receptor is intensely produced in the early stage of cancer development and it may take part in the carcinogenic processes of ESCC.
adipokines, apelin, esophageal squamous cell carcinoma, apelin receptor
- Kitayama J, Tabuchi M, Tsurita G, Ishikawa M, Otani K, Nagawa H. Adiposity and gastrointestinal malignancy. Digestion. 2009;79(Suppl 1):26–32. doi: 10.1159/000167863
- Ntikoudi E, Kiagia M, Boura P, Syrigos KN. Hormones of adipose tissue and their biologic role in lung cancer. Cancer Treat Rev. 2014;40(1):22–30. doi: 10.1016/j.ctrv.2013.06.005
- Karapanagiotou EM, Tsochatzis EA, Dilana KD, Tourkantonis I, Gratsias I, Syrigos KN. The significance of leptin, adiponectin, and resistin serum levels in non-small cell lung cancer (NSCLC). Lung Cancer. 2008;61(3):391–397. doi: 10.1016/j.lungcan.2008.01.018
- Nieman KM, Romero IL, Van Houten B, Lengyel E. Adipose tissue and adipocytes support tumorigenesis and metastasis. Biochim Biophys Acta. 2013;1831(10):1533–1541. doi: 10.1016/j.bbalip.2013.02.010
- Friedenreich CM, Biel RK, Lau DC, et al. Case-control study of the metabolic syndrome and metabolic risk factors for endometrial cancer. Cancer Epidemiol Biomarkers Prev. 2011;20(11):2384–2395. doi: 10.1158/1055–9965.EPI-11–0715
- Gonullu G, Kahraman H, Bedir A, Bektas A, Yücel I. Association between adiponectin, resistin, insulin resistance, and colorectal tumors. Int J Colorectal Dis. 2010;25(2):205–212. doi: 10.1007/s00384–009–0828–6
- Tiaka EK, Manolakis AC, Kapsoritakis AN, Potamianos SP. The implication of adiponectin and resistin in gastrointestinal diseases. Cytokine Growth Factor Rev. 2011;22(2):109–119. doi: 10.1016/j.cytogfr.2011.04.002
- Nakajima TE, Yamada Y, Hamano T, et al. Adipocytokines and squamous cell carcinoma of the esophagus. J Cancer Res Clin Oncol. 2010;136(2):261–266. doi: 10.1007/s00432–009–0657–6
- Nakayama A, Aoki S, Uchihashi K, et al. Interaction between esophageal squamous cell carcinoma and adipose tissue in vitro. Am J Pathol. 2016;186(5):1180–1194. doi: 10.1016/j.ajpath.2016.01.003
- Diakowska D, Markocka-Mączka K, Szelachowski P, Grabowski K. Serum levels of resistin, adiponectin, and apelin in gastroesophageal cancer patients. Dis Markers. 2014;2014:619649. doi: 10.1155/2014/619649
- Yildirim A, Bilici M, Cayir K, Yanmaz V, Yildirim S, Tekin SB. Serum adiponectin levels in patients with esophageal cancer. Jpn J Clin Oncol. 2009;39(2):92–96. doi: 10.1093/jjco/hyn143
- Yang Y, Lv SY, Ye W, Zhang L. Apelin/APJ system and cancer. Clin Chim Acta. 2016;457:112–116. doi: 10.1016/j.cca.2016.04.001
- Berta J, Hoda MA, Laszlo V, et al. Apelin promotes lymphangiogenesis and lymph node metastasis. Oncotarget. 2014;5(12):4426–4423.
- Nakajima TE, Yamada Y, Hamano T, et al. Adipocytokine levels in gastric cancer patients: resistin and visfatin as biomarkers of gastric cancer. J Gastroenterol. 2009;44(7):685–690. doi: 10.1007/s00535–009–0063–5
- Wu CC, Chu HW, Hsu CW, Chang KP, Liu HP. Saliva proteome profiling reveals potential salivary biomarkers for detection of oral cavity squamous cell carcinoma. Proteomics. 2015;15(19):3394–3404. doi: 10.1002/pmic.201500157
- Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001;25(4):402–408.
- Picault FX, Chaves-Almagro C, Projetti F, Prats H, Masri B, Audigier Y. Tumour co-expression of apelin and its receptor is the basis of an autocrine loop involved in the growth of colon adenocarcinomas. Eur J Cancer. 2014;50(3):663–674. doi: 10.1016/j.ejca.2013.11.017
- Berta J, Kenessey I, Dobos J, et al. Apelin expression in human non-small cell lung cancer: Role in angiogenesis and prognosis. J Thorac Oncol. 2010;5(8):1120–1129. doi: 10.1097/JTO.0b013e3181e2c1ff
- Heo K, Kim YH, Sung HJ, et al. Hypoxia-induced up-regulation of apelin is associated with a poor prognosis in oral squamous cell carcinoma patients. Oral Oncol. 2012;48(6):500–506. doi: 10.1016/j.oraloncology.2011.12.015
- Sorli SC, Le Gonidec S, Knibiehler B, Audigier Y. Apelin is a potent activator of tumour neoangiogenesis. Oncogene. 2007;26(55):7692–7699.
- Kälin RE, Kretz MP, Meyer AM, Kispert A, Heppner FL, Brändli AW. Paracrine and autocrine mechanisms of apelin signaling govern embryonic and tumor angiogenesis. Dev Biol. 2007;305(2):599–614.
- Filková M, Haluzík M, Gay S, Senolt L. The role of resistin as a regulator of inflammation: Implications for various human pathologies. Clin Immunol. 2009;133(2):157–170. doi: 10.1016/j.clim.2009.07.013
- Steppan CM, Brown EJ, Wright CM, et al. A family of tissue-specific resistin-like molecules. Proc Natl Acad Sci U S A. 2001;98(2):502–506.
- Sălăgeanu A, Tucureanu C, Lerescu L, et al. Serum levels of adipokines resistin and leptin in patients with colon cancer. J Med Life. 2010;3(4):416–420.
- Tsai CH, Tsai HC, Huang HN, et al. Resistin promotes tumor metastasis by down-regulation of miR-519d through the AMPK/p38 signaling pathway in human chondrosarcoma cells. Oncotarget. 2015;6(1):258–270. doi: 10.18632/oncotarget.2724
- Hlavna M, Kohut L, Lipkova J, et al. Relationship of resistin levels with endometrial cancer risk. Neoplasma. 2011;58(2):124–128.
- Guo XH, Wang JY, Gao Y, et al. Decreased adiponectin level is associated with aggressive phenotype of tongue squamous cell carcinoma. Cancer Sci. 2013;104(2):206–213. doi: 10.1111/cas.12077
- Kerem M, Ferahkose Z, Yilmaz UT, et al. Adipokines and ghrelin in gastric cancer cachexia. World J Gastroenterol. 2008;14(23):3633–3641.
- Batista ML Jr, Olivan M, Alcantara PS, et al. Adipose tissue-derived factors as potential biomarkers in cachectic cancer patients. Cyto-kine. 2013;61(2):532–539. doi: 10.1016/j.cyto.2012.10.023
- de Carvalho TM, Miguel Marin D, da Silva CA, et al. Evaluation of patients with head and neck cancer performing standard treatment in relation to body composition, resting metabolic rate, and inflammatory cytokines. Head Neck. 2015;37(1):97–102. doi: 10.1002/hed.23568
- Gulen ST, Karadag F, Karul AB, et al. Adipokines and systemic inflammation in weight-losing lung cancer patients. Lung. 2012;190(3):327–332. doi: 10.1007/s00408–011–9364–6
- Young MR, Levingston C, Johnson SD. Cytokine and adipokine levels in patients with premalignant oral lesions or in patients with oralcancer who did or did not receive 1α,25-Dihydroxyvitamin D3 treatment upon cancer diagnosis. Cancers (Basel). 2015;7(3):1109–1124. doi: 10.3390/cancers7030827
- 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;20:2351–2357. doi: 10.12659/MSM.891088