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Hajati, A., Talebian, F., Babahajian, A., Daneshkhah, N., & Ghaderi, B. (2022). Association of Serum Leptin with Prognostic Factors in Breast Cancer. Sudan Journal of Medical Sciences (SJMS), 17(1), 4-14. https://doi.org/10.18502/sjms.v17i1.10681
https://doi.org/10.18502/sjms.v17i1.10681
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Amirreza Hajati
Amirreza Hajati
Liver and Digestive Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran
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Farshad Talebian
Farshad Talebian
Student Research Committee, Kurdistan University of Medical Sciences, Sanandaj, Iran
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Asrin Babahajian
Asrin Babahajian
Liver and Digestive Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran
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Nasrin Daneshkhah
Nasrin Daneshkhah
Faculty of Nursing and Midwifery, Kurdistan University of Medical Sciences, Sanandaj, Iran
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Bayazid Ghaderi
Bayazid Ghaderi
Liver and Digestive Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran
Published Date
- Mar 31, 2022
Association of Serum Leptin with Prognostic Factors in Breast Cancer
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 age- and 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.
Keywords:
leptin, breast cancer, staging, grading
References
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[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.
[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.