Association of Serum Leptin with Prognostic Factors in Breast Cancer
Keywords:
leptin, breast cancer, staging, grading
Abstract
Background: Nowadays, cytokines such as Leptin and adiponectin are introduced as
prognostic factors which, according to some studies, are also associated with body
mass index. This study aimed to determine serum leptin level and its relationship with
prognostic factors in breast cancer patients.
Methods: This case–control study was conducted in the oncology department of Tohid
Hospital, Sanandaj, Iran, between 2019 and 2020. Hundred new cases of breast cancer
patients with histological evidence were enrolled in this study. Additionally, 100 ageand
BMI-matched healthy individuals were recruited as the control group. The serum
leptin level was measured using the ELISA method.
Results: Serum leptin levels were significantly higher in breast cancer patients
compared to the control group (21.68 ± 9.16 vs 11.89 ± 4.45; p < 0.001). There
was no significant relationship between plasma leptin levels with ER, PR, and HER2
expressions (p > 0.05). Also, no significant associations were noted between leptin
levels and grading and disease staging (p > 0.05).
Conclusion: The study found that leptin is higher in breast cancer patients than in
healthy individuals, however, it did not prove that leptin is a predictive or prognostic
factor.
References
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Cancer Prevention Research, vol. 6, no. 3, pp. 188–195.
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of serum adipokines: Leptin, resistin and visfatin in postmenopausal breast cancer.
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receptor in breast cancer patients′ serum and the clinical significance. International
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[31] Grossmann, M. E. and Cleary, M. P. (2012). The balance between Leptin and
adiponectin in the control of carcinogenesis–focus on mammary tumorigenesis.
Biochimie, vol. 94, no. 10, pp. 2164–2171.
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breast cancer: a meta-analysis. PloS One, vol. 8, no. 6, p. e67349.
[33] Pan, H., Deng, L.-L., Cui, J.-Q., et al. (2018). Association between serum leptin levels
and breast cancer risk: an updated systematic review and meta-analysis. Medicine,
vol. 97, no. 27, p. e11345.
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leptin concentration and G-2548A gene polymorphism in patients with breast cancer:
a meta-analysis. Archives of Medical Science, vol. 15, no. 2, pp. 275–283.
[35] Wang, Y., Cheng, X., and Xiu-Juan, L. (2013). The expression of leptin receptor in
breast cancer and the relationship with clinical prognosis. China Practical Medicine,
vol. 2013, p. 14.
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as a link between metabolism and the immune system. Cytokine & growth Factor
Reviews, vol. 35, pp. 71–84.
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epithelial cells of mouse MMTV-Wnt-1 mammary tumors. Journal of Cancer Research
and Clinical Oncology, vol. 138, no. 9, pp. 1607–1612.
[38] Shrestha, M. and Park, P.-H. (2016). p53 signaling is involved in leptin-induced
growth of hepatic and breast cancer cells. The Korean Journal of Physiology &
Pharmacology, vol. 20, no. 5, p. 487.
[39] Mahbouli, S., Der Vartanian, A., Ortega, S., et al. (2017). Leptin induces ROS via
NOX5 in healthy and neoplastic mammary epithelial cells. Oncology Reports, vol.
38, no. 5, pp. 3254–3264.
[40] Nadal-Serrano, M., Sastre-Serra, J., Valle, A., et al. (2015). Chronic-leptin attenuates
Cisplatin cytotoxicity in MCF-7 breast cancer cell line. Cellular Physiology and
Biochemistry, vol. 36, no. 1, pp. 221–232.
[41] Barone, I., Catalano, S., Gelsomino, L., et al. (2012). Leptin mediates tumor–stromal
interactions that promote the invasive growth of breast cancer cells. Cancer
Research, vol. 72, no. 6, pp. 1416–1427.
[42] Li, K., Wei, L., Huang, Y., et al. (2016). Leptin promotes breast cancer cell migration
and invasion via IL-18 expression and secretion. International Journal of Oncology,
vol. 48, no. 6, pp. 2479–2487.
[43] Al-Khalaf, H. H., Amir, M., Al-Mohanna, F., et al. (2017). Obesity and p16INK4A
downregulation activate breast adipocytes and promote their protumorigenicity.
Molecular and Cellular Biology, vol. 37, no. 17, p. e00101-17.
[44] Liu, C.-L., Chang, Y.-C., Cheng, S.-P., et al. (2007). The roles of serum leptin
concentration and polymorphism in leptin receptor gene at codon 109 in breast
cancer. Oncology, vol. 72, no. 1–2, pp. 75–81.
[45] Kim, Y., Kim, S.-Y., Lee, J. J., et al. (2006). Effects of the expression of leptin and leptin
receptor (OBR) on the prognosis of early-stage breast cancers. Cancer Research
and Treatment, vol. 38, no. 3, p. 126.
cancer in 20 to 69 years old women. Iranian Quarterly Journal of Breast Disease,
vol. 7, no. 2, pp. 67–75.
[2] Nikmanesh, Z. (2013). Prediction of posttraumatic growth base on of spirituality and
social support in patients with breast cancer. Iranian Quarterly Journal of Breast
Disease, vol. 6, no. 2, pp. 35–42.
[3] Ghanbari, S. (2013). Survey of the effect of Occupational Therapy program pamphlet
on Quality of Life in women with Breast Cancer. Iranian Quarterly Journal of Breast
Disease, vol. 6, no. 2, pp. 43–49.
[4] Lamont, E. B., Herndon, J. E., Weeks, J. C., et al. (2006). Measuring disease-free
survival and cancer relapse using Medicare claims from CALGB breast cancer trial
participants (companion to 9344). Journal of the National Cancer Institute, vol. 98,
no. 18, pp. 1335–1338.
[5] Li, C. (2010). Breast cancer epidemiology: Springer.
[6] Sánchez-Jiménez, F., Pérez-Pérez, A., de la Cruz-Merino, L., et al. (2019). Obesity and
breast cancer: role of leptin. Frontiers in Oncology, vol. 9, p. 596.
[7] Ray, A. (2018). Cancer and comorbidity: the role of Leptin in breast cancer and
associated pathologies. World Journal of Clinical Cases, vol. 6, no. 12, p. 483.
[8] Monteleone, P. and Maj, M. (2013). Dysfunctions of Leptin, ghrelin, BDNF and
endocannabinoids in eating disorders: beyond the homeostatic control of food
intake. Psychoneuroendocrinology, vol. 38, no. 3, pp. 312–330.
[9] Fan, S.-H. and Say, Y.-H. (2014). Leptin and leptin receptor gene polymorphisms and
their association with plasma leptin levels and obesity in a multi-ethnic Malaysian
suburban population. Journal of Physiological Anthropology, vol. 33, no. 1, pp. 1–10.
[10] Zavalza-Gómez, A. B., Anaya-Prado, R., Rincón-Sánchez, A. R., et al. (2008).
Adipokines and insulin resistance during pregnancy. Diabetes Research and Clinical
Practice, vol. 80, no. 1, pp. 8–15.
[11] Schanton, M., Maymó, J. L., Pérez-Pérez, A., et al. (2018). Involvement of leptin in the
molecular physiology of the placenta. Reproduction, vol. 155, no. 1, pp. R1–R12.
[12] Dalamaga, M. (2013). Obesity, insulin resistance, adipocytokines and breast cancer:
new biomarkers and attractive therapeutic targets. World Journal of Experimental
Medicine, vol. 3, no. 3, p. 34.
[13] Coskun, U., Günel, N., Toruner, F., et al. (2003). Serum leptin, prolactin and vascular
endothelial growth factor (VEGF) levels in patients with breast cancer. Neoplasma,
vol. 50, no. 1, pp. 41–46.
[14] Harris, H. R., Tworoger, S. S., Hankinson, S. E., et al. (2011). Plasma leptin levels and
risk of breast cancer in premenopausal women. Cancer Prevention Research, vol.
4, no. 9, pp. 1449–1456.
[15] da Silva, M., Weiderpass, E., Licaj, I., et al. (2018). Excess body weight, weight gain
and obesity-related cancer risk in women in Norway: the Norwegian Women and
Cancer study. British Journal of Cancer, vol. 119, no. 5, pp. 646–656.
[16] Dobbins, M., Decorby, K., and Choi, B. (2013). The association between obesity and
cancer risk: a meta-analysis of observational studies from 1985 to 2011. International
Scholarly Research Notices, vol. 2013, article 680536.
[17] Garofalo, C. and Surmacz, E. (2006). Leptin and cancer. Journal of Cellular
Physiology, vol. 207, no. 1, pp. 12–22.
[18] Porter, G. A., Inglis, K. M., Wood, L. A., et al. (2006). Effect of obesity on presentation
of breast cancer. Annals of Surgical Oncology, vol. 13, no. 3, pp. 327–332.
[19] Crean-Tate, K. K. and Reizes, O. (2018). Leptin regulation of cancer stem cells in
breast and gynecologic cancer. Endocrinology, vol. 159, no. 8, pp. 3069–3080.
[20] Jenks, M. Z., Fairfield, H. E., Johnson, E. C., et al. (2017). Sex steroid hormones
regulate leptin transcript accumulation and protein secretion in 3T3-L1 cells. Scientific
Reports, vol. 7, no. 1, p. 8232.
[21] Wang, T., Zhang, Z., Wang, K., et al. (2017). Inhibitory effects of BMP9 on breast cancer
cells by regulating their interaction with pre-adipocytes/adipocytes. Oncotarget, vol.
8, no. 22, p. 35890.
[22] Rodrigo, C., Tennekoon, K. H., Karunanayake, E. H., et al. (2017). Circulating leptin,
soluble leptin receptor, free leptin index, visfatin and selected leptin and leptin
receptor gene polymorphisms in sporadic breast cancer. Endocrine Journal, vol. 64,
no. 4, pp. 393–401.
[23] El-Hussiny, M. A.-B., Atwa, M. A., Rashad, W. E., et al. (2017). Leptin receptor
Q223R polymorphism in Egyptian female patients with breast cancer. Contemporary
Oncology, vol. 21, no. 1, p. 42.
[24] Mohammadzadeh, G., Ghaffari, M.-A., Bafandeh, A., et al. (2015). The relationship
between-2548 G/A leptin gene polymorphism and risk of breast cancer and serum
leptin levels in Ahvazian women. Iranian Journal of Cancer Prevention, vol. 8, no. 2,
p. 100.
[25] Geisler, J., Haynes, B., Ekse, D., et al. (2007). Total body aromatization in
postmenopausal breast cancer patients is strongly correlated to plasma leptin levels.
The Journal of Steroid Biochemistry and Molecular Biology, vol. 104, no. 1–2, pp.
27–34.
[26] Ollberding, N. J., Kim, Y., Shvetsov, Y. B., et al. (2013). Prediagnostic Leptin,
adiponectin, C-reactive protein, and the risk of postmenopausal breast cancer.
Cancer Prevention Research, vol. 6, no. 3, pp. 188–195.
[27] Assiri, A. M. and Kamel, H. F. (2016). Evaluation of diagnostic and predictive value
of serum adipokines: Leptin, resistin and visfatin in postmenopausal breast cancer.
Obesity Research & Clinical Practice, vol. 10, no. 4, pp. 442–453.
[28] Chen, D.-C., Chung, Y.-F., Yeh, Y.-T., et al. (2006). Serum adiponectin and leptin levels
in Taiwanese breast cancer patients. Cancer Letters, vol. 237, no. 1, pp. 109–114.
[29] Wang, Y., Yao, W., Wang, B., et al. (2015). The expression of Leptin and soluble leptin
receptor in breast cancer patients′ serum and the clinical significance. International
Journal of Laboratory Medicine, vol. 10, pp. 1341–1343.
[30] Gu, L., Wang, C.-D., Cao, C., et al. (2019). Association of serum leptin with breast
cancer: a meta-analysis. Medicine, vol. 98, no. 5, p. e14094.
[31] Grossmann, M. E. and Cleary, M. P. (2012). The balance between Leptin and
adiponectin in the control of carcinogenesis–focus on mammary tumorigenesis.
Biochimie, vol. 94, no. 10, pp. 2164–2171.
[32] Niu, J., Jiang, L., Guo, W., et al. (2013). The association between leptin level and
breast cancer: a meta-analysis. PloS One, vol. 8, no. 6, p. e67349.
[33] Pan, H., Deng, L.-L., Cui, J.-Q., et al. (2018). Association between serum leptin levels
and breast cancer risk: an updated systematic review and meta-analysis. Medicine,
vol. 97, no. 27, p. e11345.
[34] Hao, J.-Q., Zhang, Q.-K., Zhou, Y.-X., et al. (2019). Association between circulating
leptin concentration and G-2548A gene polymorphism in patients with breast cancer:
a meta-analysis. Archives of Medical Science, vol. 15, no. 2, pp. 275–283.
[35] Wang, Y., Cheng, X., and Xiu-Juan, L. (2013). The expression of leptin receptor in
breast cancer and the relationship with clinical prognosis. China Practical Medicine,
vol. 2013, p. 14.
[36] Pérez-Pérez, A., Vilariño-García, T., Fernández-Riejos, P., et al. (2017). Role of leptin
as a link between metabolism and the immune system. Cytokine & growth Factor
Reviews, vol. 35, pp. 71–84.
[37] Zheng, Q., Hursting, S. D., and Reizes, O. (2012). Leptin regulates cyclin D1 in luminal
epithelial cells of mouse MMTV-Wnt-1 mammary tumors. Journal of Cancer Research
and Clinical Oncology, vol. 138, no. 9, pp. 1607–1612.
[38] Shrestha, M. and Park, P.-H. (2016). p53 signaling is involved in leptin-induced
growth of hepatic and breast cancer cells. The Korean Journal of Physiology &
Pharmacology, vol. 20, no. 5, p. 487.
[39] Mahbouli, S., Der Vartanian, A., Ortega, S., et al. (2017). Leptin induces ROS via
NOX5 in healthy and neoplastic mammary epithelial cells. Oncology Reports, vol.
38, no. 5, pp. 3254–3264.
[40] Nadal-Serrano, M., Sastre-Serra, J., Valle, A., et al. (2015). Chronic-leptin attenuates
Cisplatin cytotoxicity in MCF-7 breast cancer cell line. Cellular Physiology and
Biochemistry, vol. 36, no. 1, pp. 221–232.
[41] Barone, I., Catalano, S., Gelsomino, L., et al. (2012). Leptin mediates tumor–stromal
interactions that promote the invasive growth of breast cancer cells. Cancer
Research, vol. 72, no. 6, pp. 1416–1427.
[42] Li, K., Wei, L., Huang, Y., et al. (2016). Leptin promotes breast cancer cell migration
and invasion via IL-18 expression and secretion. International Journal of Oncology,
vol. 48, no. 6, pp. 2479–2487.
[43] Al-Khalaf, H. H., Amir, M., Al-Mohanna, F., et al. (2017). Obesity and p16INK4A
downregulation activate breast adipocytes and promote their protumorigenicity.
Molecular and Cellular Biology, vol. 37, no. 17, p. e00101-17.
[44] Liu, C.-L., Chang, Y.-C., Cheng, S.-P., et al. (2007). The roles of serum leptin
concentration and polymorphism in leptin receptor gene at codon 109 in breast
cancer. Oncology, vol. 72, no. 1–2, pp. 75–81.
[45] Kim, Y., Kim, S.-Y., Lee, J. J., et al. (2006). Effects of the expression of leptin and leptin
receptor (OBR) on the prognosis of early-stage breast cancers. Cancer Research
and Treatment, vol. 38, no. 3, p. 126.
