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No AccessJournal of UrologyInvestigative urology1 Oct 2006

Increased Serum Leptin Levels and Over Expression of Leptin Receptors are Associated With the Invasion and Progression of Renal Cell Carcinoma

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Purpose:

Leptin, an adipocyte derived cytokine that is closely associated with obesity, was recently shown to be involved in carcinogenesis and cancer progression. Because obesity is a significant risk factor for renal cell carcinoma, we investigated the link between leptin and the development of renal cell carcinoma.

Materials and Methods:

Associations between preoperative serum leptin levels and leptin receptor expression in tumor specimens and various clinicopathological parameters were analyzed in 57 patients with renal cell carcinoma.

Results:

Serum leptin levels were 1.2 to 16.2 ng/ml (mean 4.5). Of 57 tumors 22 (38.6%) demonstrated high leptin receptor expression. Serum leptin levels were significantly higher in patients with vs without tumor specimen venous invasion (p = 0.030) and higher in patients with high vs low leptin receptor expression (p = 0.019). There were significant associations between high leptin receptor expression and the presence of venous invasion (p = 0.013), histological type (p = 0.0076) and regional lymph node metastasis (p = 0.047). Of 42 patients with N0M0 disease those with serum leptin 5.0 ng/ml or more had significantly shorter progression-free survival than patients with lower levels (p = 0.0043). Multivariate Cox proportional hazards model analysis demonstrated that higher serum leptin was an independent predictor of progression-free survival (p = 0.0406).

Conclusions:

Leptin and leptin receptor could have a key role in the invasion of renal cell carcinoma and they could be valuable predictors of progression.

References

  • 1 : Recombinant ob protein reduces feeding and body weight in the ob/ob mouse. J Clin Invest1995; 96: 2065. Google Scholar
  • 2 : Leptin in the regulation of immunity, inflammation, and hematopoiesis. J Leukoc Biol2000; 68: 437. Google Scholar
  • 3 : Biological action of leptin as an angiogenic factor. Science1998; 281: 1683. Google Scholar
  • 4 : Leptin induces endothelial cell migration through Akt, which is inhibited by PPARgamma-ligands. Hypertension2002; 40: 748. Google Scholar
  • 5 : Leptin—a growth factor in normal and malignant breast cells and for normal mammary gland development. J Natl Cancer Inst2002; 94: 1704. Google Scholar
  • 6 : Identification of leptin receptors in human breast cancer: functional activity in the T47-D breast cancer cell line. Mol Cell Endocrinol2002; 188: 219. Google Scholar
  • 7 : Leptin mediates a proliferative response in human MCF7 breast cancer cells. Biochem Biophys Res Commun2002; 293: 622. Google Scholar
  • 8 : Leptin is associated with increased prostate cancer risk: a nested case-referent study. J Clin Endocrinol Metab2001; 86: 1341. Google Scholar
  • 9 : Adipocyte expression and circulating levels of leptin increase in both gynaecological and breast cancer patients. Int J Oncol2004; 24: 1529. Google Scholar
  • 10 : Obesity and colon cancer: does leptin provide a link?. Int J Cancer2004; 109: 149. Google Scholar
  • 11 : Enhanced expression of leptin and leptin receptor (OB-R) in human breast cancer. Clin Cancer Res2004; 10: 4325. Google Scholar
  • 12 : Subcutaneous interleukin-2 and interferon alfa administration in patients with metastatic renal cell carcinoma: final results of SCAPP III, a large, multicenter, phase II, nonrandomized study with sequential analysis design. J Clin Oncol2003; 21: 3987. Google Scholar
  • 13 : Obesity, hypertension, and renal cancer. N Engl J Med2001; 344: 531. Google Scholar
  • 14 : Obesity, interrelated mechanisms, and exposures and kidney cancer. Semin Urol Oncol2001; 19: 270. Google Scholar
  • 15 : Activation of signal transducer and activator of transcription 3 in renal cell carcinoma: a study of incidence and its association with pathological features and clinical outcome. J Urol2002; 168: 762. LinkGoogle Scholar
  • 16 : Leptin influences cellular differentiation and progression in prostate cancer. J Urol2003; 169: 1308. LinkGoogle Scholar
  • 17 : Serum insulin-like growth factor-1 is an independent predictor of prognosis in patients with renal cell carcinoma. Acta Oncol2004; 43: 744. Google Scholar
  • 18 : Re: leptin—a growth factor in normal and malignant breast cells and for normal mammary gland development. J Natl Cancer Inst2003; 95: 1171. Google Scholar
  • 19 : Leptin promotes invasiveness of kidney and colonic epithelial cells via phosphoinositide 3-kinase-, rho-, and rac-dependent signaling pathways. Faseb J2000; 14: 2329. Google Scholar
  • 20 : Expression of the free beta-subunit of human chorionic gonadotropin in renal cell carcinoma: prognostic study on tissue and serum. Int J Cancer2003; 104: 631. Google Scholar
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