Skip to main content
Log in

Clinical significance of serum adipokines levels in lung cancer

  • Original Paper
  • Published:
Medical Oncology Aims and scope Submit manuscript

Abstract

Adipokines have a significant effect on metabolism, immunoinflammatory responses as well as on carcinogenesis; therefore, we aimed at evaluating their potential predictive and prognostic significance in lung cancer. Eighty patients—mean age 62.9 ± 9.2 years—with previously untreated lung cancer (61 NSCLC and 19 SCLC) of all stages and 40 healthy individuals were enrolled in this study. Serum levels of leptin, adiponectin and ghrelin were measured using human Radioimmunoassay kits. Serum leptin levels in lung cancer patients were lower compared to control (p < 0.0001), while adiponectin and ghrelin levels were significantly increased in patients (p = 0.0003 and p = 0.0043, respectively). Additionally, the leptin/adiponectin ratio was significantly lower in the patients group compared to controls (p < 0.0001]. There was no association between serum levels of adipokines and any of the patient clinicopathological characteristics or response to therapy. Nevertheless, patients with lower values of serum leptin had shorter overall survival (p = 0.014), whereas multivariate analysis revealed leptin levels as an independent prognostic factor for survival (p = 0.024, HR 0.452, CI 95 % 0.232–0.899). These results suggest that adipokines may play a role in the pathogenesis of lung cancer, while leptin serum levels might provide useful prognostic information.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin. 2010;60:277–300.

    Article  PubMed  Google Scholar 

  2. Vona-Davis L, Rose DP. Adipokines as endocrine, paracrine, and autocrine factors in breast cancer risk and progression. Endocr Relat Cancer. 2007;14:189–206.

    Article  PubMed  CAS  Google Scholar 

  3. Bouloumie A, Drexler HC, Lafontan M, Busse R. Leptin, the product of Ob gene, promotes angiogenesis. Circ Res. 1998;83:1059–66.

    Article  PubMed  CAS  Google Scholar 

  4. Kume K, Satomura K, Nishisho S, Kitaoka E, Yamanouchi K, Tobiume S, et al. Potential role of leptin in endochondral ossification. J Histochem Cytochem. 2002;50:159–69.

    Article  PubMed  CAS  Google Scholar 

  5. Artwohl M, Roden M, Hölzenbein T, Freudenthaler A, Waldhäusl W, Baumgartner-Parzer SM. Modulation by leptin of proliferation and apoptosis in vascular endothelial cells. Int J Obes Relat Metab Disord. 2002;26:577–80.

    Article  PubMed  CAS  Google Scholar 

  6. Cascio S, Bartella V, Auriemma A, Johannes GJ, Russo A, Giordano A, et al. Mechanism of leptin expression in breast cancer cells: role of hypoxia-inducible factor-1alpha. Oncogene. 2008;27:540–7.

    Article  PubMed  CAS  Google Scholar 

  7. Wang SN, Yeh YT, Yang SF, Chai CY, Lee KT. Potential role of leptin expression in hepatocellular carcinoma. J Clin Pathol. 2006;59:930–4.

    Article  PubMed  Google Scholar 

  8. Ribeiro R, Araújo AP, Coelho A, Catarino R, Pinto D, Araújo A, et al. A functional polymorphism in the promoter region of leptin gene increases susceptibility for non-small cell lung cancer. Eur J Cancer. 2006;42:1188–93.

    Article  PubMed  CAS  Google Scholar 

  9. Alemán MR, Santolaria F, Batista N, de La Vega M, González-Reimers E, Milena A, et al. Leptin role in advanced lung cancer. A mediator of the acute phase response or a marker of the status of nutrition? Cytokine. 2002;19:21–6.

    Article  PubMed  Google Scholar 

  10. Jamieson NB, Brown DJ, Wallace MA, McMillan DC. Adiponectin and the systemic inflammatory response in weight-losing patients with non-small cell lung cancer. Cytokine. 2004;27:90–2.

    Article  PubMed  CAS  Google Scholar 

  11. Karapanagiotou EM, Tsochatzis EA, Dilana KD, Tourkantonis I, Gratsias I, Syrigos KN, et al. The significance of leptin, adiponectin, and resistin serum levels in non-small cell lung cancer (NSCLC). Lung Cancer. 2008;61:391–7.

    Article  PubMed  Google Scholar 

  12. Terzidis A, Sergentanis TN, Antonopoulos G, Syrigos C, Efremidis A, Polyzos A, et al. Elevated serum leptin levels: a risk factor for non-small-cell lung cancer? Oncology. 2009;76:19–25.

    Article  PubMed  CAS  Google Scholar 

  13. Carpagnano GE, Spanevello A, Curci C, Salerno F, Palladino GP, Resta O, et al. IL-2, TNF-alpha, and leptin: local versus systemic concentrations in NSCLC patients. Oncol Res. 2007;16:375–81.

    PubMed  Google Scholar 

  14. Arditi JD, Venihaki M, Karalis KP, Chrousos GP. Antiproliferative effect of adiponectin on MCF7 breast cancer cells: a potential hormonal link between obesity and cancer. Horm Metab Res. 2007;39:9–13.

    Article  PubMed  CAS  Google Scholar 

  15. Barb D, Neuwirth A, Mantzoros CS, Balk SP. Adiponectin signals in prostate cancer cells through Akt to activate the mammalian target of rapamycin pathway. Endocr Relat Cancer. 2007;14:995–1005.

    Article  PubMed  CAS  Google Scholar 

  16. Petridou ET, Mitsiades N, Gialamas S, Angelopoulos M, Skalkidou A, Dessypris N, et al. Circulating adiponectin levels and expression of adiponectin receptors in relation to lung cancer: two case-control studies. Oncology. 2007;73:261–9.

    Article  PubMed  CAS  Google Scholar 

  17. Barb D, Williams CJ, Neuwirth AK, Mantzoros CS. Adiponectin in relation to malignancies: a review of existing basic research and clinical evidence. Am J Clin Nutr. 2007;86:s858–s866 (review).

    Google Scholar 

  18. Guadagni F, Roselli M, Martini F, Spila A, Riondino S, D’Alessandro R, et al. Prognostic significance of serum adipokine levels in colorectal cancer patients. Anticancer Res. 2009;29:3321–7.

    PubMed  CAS  Google Scholar 

  19. Ashizawa N, Yahata T, Quan J, Adachi S, Yoshihara K, Tanaka K. Serum leptin-adiponectin ratio and endometrial cancer risk in postmenopausal female subjects. Gynecol Oncol. 2010;119:65–9.

    Article  PubMed  CAS  Google Scholar 

  20. Nakazato M, Murakami N, Date Y, Kojima M, Matsuo H, Kangawa K. A role for ghrelin in the central regulation of feeding. Nature. 2001;409:194–8.

    Article  PubMed  CAS  Google Scholar 

  21. Garcia JM, Garcia-Touza M, Hijazi RA, Taffet G, Epner D, Mann D, et al. Active ghrelin levels and active to total ghrelin ratio in cancer-induced cachexia. J Clin Endocrinol Metab. 2005;90:2920–6.

    Article  PubMed  CAS  Google Scholar 

  22. Wolf I, Sadetzki S, Kanety H, Kundel Y, Pariente C, Epstein N, et al. Adiponectin, ghrelin, and leptin in cancer cachexia in breast and colon cancer patients. Cancer. 2006;106:966–73.

    Article  PubMed  CAS  Google Scholar 

  23. Cassoni P, Allia E, Marrocco T, Papotti M. Ghrelin and cortistatin in lung cancer: expression of peptides and related receptors in human primary tumors and in vitro effect on the H345 small cell carcinoma cell line. J Endocrinol Invest. 2006;29:781–90.

    PubMed  CAS  Google Scholar 

  24. Yeh AH, Jeffery PL, Duncan RP, Herington AC, Chopin LK. Ghrelin and a novel preproghrelin isoform are highly expressed in prostate cancer and ghrelin activates mitogen-activated protein kinase in prostate cancer. Clin Cancer Res. 2005;11:8295–303.

    Article  PubMed  CAS  Google Scholar 

  25. Jeffery PL, Murray RE, Yeh AH, McNamara JF, Duncan RP, Francis GD, et al. Expression and function of the ghrelin axis, including a novel preproghrelin isoform, in human breast cancer tissues and cell lines. Endocr Relat Cancer. 2005;12:839–50.

    Article  PubMed  CAS  Google Scholar 

  26. Karapanagiotou EM, Polyzos A, Dilana KD, Gratsias I, Boura P, Gkiozos I, et al. Increased serum levels of ghrelin at diagnosis mediate body weight loss in non-small cell lung cancer (NSCLC) patients. Lung Cancer. 2009;66:393–8.

    Article  PubMed  Google Scholar 

  27. Shimizu Y, Nagaya N, Isobe T, Imazu M, Okumura H, Hosoda H, Kojima M, Kangawa K, Kohno N. Increased plasma ghrelin level in lung cancer cachexia. Clin Cancer Res. 2003;9:774–8.

    PubMed  CAS  Google Scholar 

  28. Tas F, Duranyildiz D, Argon A, Oğuz H, Camlica H, Yasasever V, et al. Serum levels of leptin and proinflammatory cytokines in advanced-stage non-small cell lung cancer. Med Oncol. 2005;22:353–8.

    Article  PubMed  CAS  Google Scholar 

  29. Mantzoros CS, Moschos S, Avramopoulos I, Kaklamani V, Liolios A, Doulgerakis DE, et al. Leptin concentrations in relation to body mass index and the tumor necrosis factor-alpha system in humans. J Clin Endocrinol Metab. 1997;82:3408–13.

    Article  PubMed  CAS  Google Scholar 

  30. Supervνa A, Enjuanes A, Vila J, Mellibovsky L, Noguιs X, Dνez-Pιrez A. Effect of tobacco smoking on leptin serum levels and its relationship with steroid hormones and bone mineral density. Med Clin. 2006;127:645–7.

    Article  Google Scholar 

  31. Zhao X, Huang K, Zhu Z, Chen S, Hu R. Correlation between expression of leptin and clinicopathological features and prognosis in patients with gastric cancer. J Gastroenterol Hepatol. 2007;22:1317–21.

    Article  PubMed  CAS  Google Scholar 

  32. Wang SN, Yeh YT, Yang SF, Chai CY, Lee KT. Potential role of leptin expression in hepatocellular carcinoma. J Clin Pathol. 2006;59:930–4.

    Article  PubMed  Google Scholar 

  33. Guadagni F, Roselli M, Martini F, Spila A, Riondino S, D’Alessandro R, et al. Prognostic significance of serum adipokine levels in colorectal cancer patients. Anticancer Res. 2009;29:3321–7.

    PubMed  CAS  Google Scholar 

  34. Ribeiro R, Araújo A, Lopes C, Medeiros R. Immunoinflammatory mechanisms in lung cancer development: is leptin a mediator? J Thorac Oncol. 2007;2:105–8.

    PubMed  Google Scholar 

  35. Paik SS, Jang SM, Jang KS, Lee KH, Choi D, Jang SJ. Leptin expression correlates with favorable clinicopathologic phenotype and better prognosis in colorectal adenocarcinoma. Ann Surg Oncol. 2009;16:297–303.

    Article  PubMed  Google Scholar 

  36. Bråkenhielm E, Veitonmäki N, Cao R, Kihara S, Matsuzawa Y, Zhivotovsky B, et al. Adiponectin-induced antiangiogenesis and antitumor activity involve caspase-mediated endothelial cell apoptosis. Proc Natl Acad Sci U S A. 2004;101:2476–81.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Theodora Kerenidi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kerenidi, T., Lada, M., Tsaroucha, A. et al. Clinical significance of serum adipokines levels in lung cancer. Med Oncol 30, 507 (2013). https://doi.org/10.1007/s12032-013-0507-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12032-013-0507-x

Keywords

Navigation