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Original Research

Open Access

Role of adiponectin and leptin in non-diabetic, non-obese patients with endometrial cancer

  • T. Ueno1
  • H. Yabushita1,*,
  • K.Iwasaki1
  • A. Wakatsuki1

1Department of Obstetrics and Gynecology, Aichi Medical University, School of Medicine, Nagakute (Japan)

DOI: 10.12892/ejgo3689.2018 Vol.39,Issue 2,April 2018 pp.199-204

Published: 10 April 2018

*Corresponding Author(s): H. Yabushita E-mail: yab@aichi-med-u.ac.jp

Abstract

Objective: To clarify the roles of adiponectin and leptin in endometrial cancer, this study examined serum concentrations of adiponectin and leptin, intra-tumor expression of two adiponectin receptors (AdipoR-1 and AdipoR-2) and the leptin receptor (ObR), and analyzed their relationship to clinicopathological parameters in non-diabetic, non-obese patients with endometrial cancer. Materials and Methods: Samples were obtained from 50 patients with endometrial cancer with fasting blood glucose levels < 120 mg/dl and body mass indices < 30. Serum concentrations of adiponectin, high-molecular weight (HMW) adiponectin, and leptin were measured by immunoassays. Expression of AdipoR-1, AdipoR-2, and ObR in tumor tissue was examined by immunohistochemical staining. Results: In endometrial cancer, serum concentrations of adiponectin were higher in patients with G1 or G2 tumors and in patients without lymphovascular space involvement. In 32 patients with AdipoR-1-positive tumors, serum concentrations of adiponectin, HMW adiponectin, and leptin did not differ by any pathological parameter. In contrast, in 18 patients with AdipoR-1-negative tumors, serum adiponectin concentrations were higher in patients with G1 or G2 tumors and in patients without lymphovascular space involvement. High histological grade, positive peritoneal cytology, lymphovascular space involvement, negative AdipoR-1 expression, and lower serum adiponectin levels were associated with poor disease-free survival by univariate regression analysis. In patients with AdipoR1-negative tumors, disease-free survival was shorter in cases with serum adiponectin concentrations < 11 μg/ml. Conclusion: Decreased serum adiponectin concentrations combined with the absence of AdipoR-1 expression in tumors are associated with high-grade tumor, lymphovascular space involvement, and poor prognosis in patients with endometrial cancer.

Keywords

Endometrial cancer; Adiponectin; Leptin; Adiponectin receptor.

Cite and Share

T. Ueno,H. Yabushita,K.Iwasaki,A. Wakatsuki. Role of adiponectin and leptin in non-diabetic, non-obese patients with endometrial cancer. European Journal of Gynaecological Oncology. 2018. 39(2);199-204.

References

[1] Matsuda T., Marugame T., Kamo K., Katanoda K., Ajiki W., Sobue T.: “Cancer incidence and incidence rates in Japan in 2006: based on data from 15 population-based cancer registries in the monitoring of cancer incidence in Japan (MCIJ) project”. Jpn. J. Clin. Oncol., 2012, 42, 139.

[2] Dal Maso L., Augustin L.S., Karalis A., Talamini R., Franceschi S., Trichopoulos D., et al.: “Circulating adiponectin and endometrial cancer risk”. J. Clin. Endocrinol. Metab., 2004, 89, 1160.

[3] Berstein L.M., Kvatchevskaya J.O., Poroshina T.E., Kovalenko I.G., Tsyrlina E.V., Zimarina T.S., et al.: “Insulin resistance, its consequences for the clinical course of the disease, and possibilities of correction in endometrial cancer”. J. Cancer Res. Clin. Oncol., 2004, 130, 687.

[4] Housa D., Housová J., Vernerová Z., Haluzík M.: “Adipocytokines and cancer”. Physiol. Res., 2006, 55, 233. [5] Garofalo C., Surmacz E.: “Leptin and cancer”. J. Cell Physiol., 2006, 207, 12.

[6] Ishikawa M., Kitayama J., Nagawa H.: “Enhanced expression of leptin and leptin receptor (OB-R) in human breast cancer”. Clin. Cancer Res., 2004; 10: 4325.

[7] Huang L., Li C.: “Leptin. a multifunctional hormone”. Cell Res., 2000; 10: 81.

[8] Garofalo C., Koda M., Cascio S., Sulkowska M., Kanczuga-Koda L., Golaszewska J., et al.: “Increased expression of leptin and the leptin receptor as a marker of breast cancer progression: possible role of obesity-related stimuli”. Clin. Cancer Res., 2006, 12, 1447.

[9] Brakenhielm E., Veitonmaki 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., 2004, 101, 2476.

[10] Yamauchi T., Kamon J., Ito Y., Tsuchida A., Yokomizo T., Kita S., et al.: “Cloning of adiponectin receptors that mediate antidiabetic metabolic effects”. Nature, 2003, 423, 762.

[11] Cong L., Gasser J., Zhao J., Yang B., Li F., Zhao A.Z.: “Human adiponectin inhibits cell growth and induces apoptosis in human endometrial carcinoma cells, HEC-1-A and RL95-2”. Endocrine Relat. Cancer, 2007, 14, 713.

[12] Rzepka-Górska I., Bedner R., Cymbaluk-PBoska A., Chudecka-Głaz A.: “Serum adiponectin in relation to endometrial cancer and endometrial hyperplasia with atypia in obese women”. Eur. J. Gynaecol. Oncol., 2008, 29, 594.

[13] Petridou E., Mantzoros C., Dessypris N., Koukoulomatis P., Addy C., Voulgaris Z., et al.: “Plasma adiponectin concentrations in relation to endometrial cancer: a case control study in Greece”. J. Clin. Endocrinol. Metab., 2003, 88, 993.

[14] Cymbaluk A., Chudecka-Glaz A., Rzepka-Gorska I.: “Leptin levels in serum depending on Body Mass Index in patients with endometrial hyperplasia and cancer”. Eur. J. Obstet. Gynecol. Reprod. Biol., 2008, 136, 74.

[15] Soliman P.T., Wu D., Tortolero-Luna G., Schmeler K.M., Slomovitz BM., Bray M.S., et al.: “Association between adiponectin, insulin resistance, and endometrial cancer”. Cancer, 2006, 106, 2376.

[16] Cust A.E., Kaaks R., Friedenreich C., Bonnet F., Laville M., Lukanova A., et al.: “Plasma adiponectin levels and endometrial cancer risk in pre- and postmenopausal women”. J. Clin. Endocrinol. Metab., 2007, 92, 255.

[17] 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.

[18] Yabushita H., Iwasaki K., Obayashi Y., Wakatsuki A.: “Clinicopathological roles of adiponectin and leptin receptors in endometrial carcinoma”. Oncol. Let., 2014, 7, 1109.

[19] Hanley A.J., Bowden D., Wagenknecht L.E., Balasubramanyam A., Langfeld C., Saad MF., et al.: “Associations of adiponectin with body fat distribution and insulin sensitivity in nondiabetic Hispanics and African-Americans”. J. Clin. Endocrinol. Metab., 2007, 92, 2665.

[20] Waki H., Yamauchi T., Kamon J., Ito Y., Uchida S., Kita S., et al.: “Impaired multimerization of human adiponectin mutants associated with diabetes. Molecular structure and multimer formation of adiponectin”. J. Biol. Chem., 2003, 278, 40352.

[21] Ohbuchi Y., Suzuki Y., Hatakeyama I., Nakao Y., Fujito A., Iwasaka T., et al.: “A lower serum level of moddle-molecular weight adiponectin is a risk factor for endometrial cancer”. Int. J. Clin. Oncol., 2014, 19, 667.

[22] Moon H.S., Chamberland J., Aronis K., Tseleni-Balafonta S., Mantzoros C.: “Direct role of adiponectin and adiponectin receptors in endometrial cancer: In vitro and ex vitro studies in humans”. Mol. Cancer Ther., 2011, 10, 2234.

[23] Febbraro T., Lengyel E., Romero I.L.: “Old drug, new trick: repurposing metformin for gynecologic cancers?” Gyncol. Oncol., 2014, 135, 614.

[24] Cantrell L.A., Zhou C., Mendivil A., Malloy K.M., Gehrig P.A., BaeJump V.L.: “Metformin is a potent inhibitor of endometrial cancer cell proliferation – implications for a novel treatment strategy”. Gynecol. Oncol., 2010, 116, 92.

[25] Mitsuhashi A., Kiyokawa T., Sato Y., Shozu M.: “Effects of metformin on endometrial cancer cell growth in vivo: a preoperative prospective trial”. Cancer, 2014, 120, 2986.

[26] Kong W., Niu X., Zeng T., Lu M., Chen L.: “Impact of treatment with metformin on adipocytokines in patients with polycystic ovary syndrome; a meta-analysis”. PLoS One, 2015, 10, e0140565.

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