Document Type : Original Research
Authors
- Mojtaba Sehhat 1
- Zahra Moshfegh Arani 2
- Niyusha Niusha Lajevardi 3
- Malek Reiesifar 4
- Fahimeh Abdi Abyaneh 3
- Zarichehr Vakili 5
1 Department of Social Medicine, School of Medicine, Kashan University of Medical Sciences, Kashan, Iran
2 Department of Pathology, School of Medicine, Kashan University of Medical Sciences, Kashan, Iran
3 School of Medicine, Kashan University of Medical Sciences, Kashan, Iran
4 Surgical Pathologist, Isfahan, Iran
5 Department of Pathology, Shahid Beheshti Hospital, Kashan University of Medical Sciences, Kashan, Iran
Abstract
Background & Objective: Endometrial carcinoma is one of the most common malignancies in women in developed countries and the fourth malignancy in Iranian women. Therefore, the identification of its causative factors is essential for the prevention, diagnosis, and treatment. This study was aimed to compare the leptin receptor (Ob-R) expression in the endometrial carcinoma cases and non-carcinoma samples.
Methods: In this case-control study, 89 samples (including 45 carcinoma and 44 non-carcinoma samples) were examined. The carcinomatous samples were selected by the census method and others were selected with random method. The data were obtained from histopathologic diagnosis, immunohistochemistry (negative, positive and intensity of immunoreactivity), age, history of diabetes, and hypertension. Ob-R expression was compared in the studied groups using Chi-square, Fisher tests and Multivariate logistic regression analysis. In all tests the level of significance was set at 0.05. The SPSS 26 was used for data analysis.
Results: The frequency of high levels of leptin receptors in the patients with endometrial carcinoma was significantly higher compared to the control group (57.8% vs. 2.3%) (P<0.05). Adjusting the effects of age, history of diabetes mellitus (DM) and hypertension (HTN) revealed that the positive-receptor group had 37.75 (95% CI; 5.18-275.04) odds of having endometrial carcinoma (P<0.001).
Conclusion: The leptin receptor may be a risk factor for the endometrial carcinoma among women tested in Kashan. Based on these results, leptin receptor might be considered as a potential biomarker for screening the endometrial carcinoma or targeting the therapeutic purposes.
Keywords
Main Subjects
- Goldblum JR, Lamps LW, McKenney J, Myers JL. Rosai and Ackerman's Surgical Pathology E-Book. Elsevier Health Sciences; 2017 Oct 25.
- Lax SF. Pathology of endometrial carcinoma. Mol Genet Endometrial Carcinoma. 2017:75-96. [DOI:10.1007/978-3-319-43139-0_3] [PMID]
- Bakkum-Gamez JN, Gonzalez-Bosquet J, Laack NN, Mariani A, Dowdy SC. Current issues in the management of endometrial cancer. In Mayo Clinic Proceedings 2008 Jan 1 (Vol. 83, No. 1, pp. 97-112). Elsevier. [DOI:10.4065/83.1.97] [PMID]
- Creasman WT, Odicino F, Maisonneuve P, Quinn MA, Beller U, Benedet JL, et al. Carcinoma of the corpus uteri. International J Gynecol Obstet. 2006;95:S105-43. [DOI:10.1016/S0020-7292(06)60031-3]
- Razik MA, Berry SE, Shaer OE, Salama K, Arab AEA. Serum Leptin / Adiponectin Ratio: A Possible Marker of Endometrial Pathologies in patients with Postmenopausal Bleeding. J Am Sci. 2013;9(3):26973.
- Mackintosh M, Crosbie E. Obesity‐driven endometrial cancer: is weight loss the answer? BJOG: Int J Obstet Gynaecol. 2013;120(7):791-4. [DOI:10.1111/1471-0528.12106] [PMID]
- Villavicencio A, Aguilar G, Argüello G, Dünner C, Gabler F, Soto E, et al. The effect of overweight and obesity on proliferation and activation of AKT and ERK in human endometria. Gynecol Oncol. 2010;117(1):96-102. [DOI:10.1016/j.ygyno.2009.12.022] [PMID]
- Liu Y, Lv L, Xiao W, Gong C, Yin J, Wang D, et al. Leptin activates STAT3 and ERK1/2 pathways and induces endometrial cancer cell proliferation. J Huazhong Univ Sci Technol. 2011;31(3):365-70. [DOI:10.1007/s11596-011-0382-7] [PMID]
- Mantzos F, Vanakara P, Samara S, Wozniak G, Kollia P, Messinis I, et al. Leptin receptor expression in neoplastic and normal ovarian and endometrial tissue. Eur J Gynaec Oncol-ISSN. 2011;32(1):2011.
- Koda M, Sulkowska M, Wincewicz A, KANCZUGA‐KODA L, Musiatowicz B, Szymanska M, et al. Expression of leptin, leptin receptor, and hypoxia‐inducible factor 1α in human endometrial cancer. Ann New York Acad Sci. 2007;1095(1):90-8. [DOI:10.1196/annals.1397.013] [PMID]
- Boroń D, Nowakowski R, Grabarek BO, Zmarzły N, Opławski M. Expression Pattern of Leptin and Its Receptors in Endometrioid Endometrial Cancer. J Clin Med. 2021;10(13):2787. [DOI:10.3390/jcm10132787] [PMID] [PMCID]
- Tartaglia LA, Dembski M, Weng X, Deng N, Culpepper J, Devos R, et al. Identification and expression cloning of a leptin receptor, OB-R. Cell. 1995;83(7):1263-71. [DOI:10.1016/0092-8674(95)90151-5] [PMID]
- Gao J, Tian J, Lv Y, Shi F, Kong F, Shi H, et al. Leptin induces functional activation of cyclooxygenase‐2 through JAK2/STAT3, MAPK/ERK, and PI3K/AKT pathways in human endometrial cancer cells. Cancer Sci. 2009;100(3):389-95. [DOI:10.1111/j.1349-7006.2008.01053.x] [PMID]
- Carino C, Olawaiye AB, Cherfils S, Serikawa T, Lynch MP, Rueda BR, et al. Leptin regulation of proangiogenic molecules in benign and cancerous endometrial cells. Int J Cancer. 2008;123(12):2782-90. [DOI:10.1002/ijc.23887] [PMID] [PMCID]
- Yuan S-SF, Tsai K-B, Chung Y-F, Chan T-F, Yeh Y-T, Tsai L-Y, et al. Aberrant expression and possible involvement of the leptin receptor in endometrial cancer. Gynecol Oncol. 2004;92(3):769-75. [DOI:10.1016/j.ygyno.2003.11.043] [PMID]
- Michalczyk K, Niklas N, Rychlicka M, Cymbaluk-Płoska A. The Influence of Biologically Active Substances Secreted by the Adipose Tissue on Endometrial Cancer. Diagnostics. 2021;11(3):494. [DOI:10.3390/diagnostics11030494] [PMID] [PMCID]
- Khabaz MN, Butt NS, Al-Maghrabi B, Anfinan N, Sait K, Al-Maghrabi J. Leptin expression in stromal cells of endometrial carcinomas is associated with advanced stage and disease recurrence. Int J Clin Exp Pathol. 2016;9(11):11774-80.
- Sharma D, Saxena N, Vertino P, Anania F. Leptin promotes the proliferative response and invasiveness in human endometrial cancer cells by activating multiple signal-transduction pathways. Endocr.-Relat Cancer. 2006;13(2):629-40. [DOI:10.1677/erc.1.01169] [PMID] [PMCID]
- Gong C, Liu Y, Xiao W, Yin J, Wang DH, Sheng H. The role of ERK1/2 in leptin promoting the proliferation of human endometrial cancer cell line Ishikawa. Ai Zheng= Aizheng= Chin J Cancer. 2007;26(11):1211-4.
- Wu X, Yan Q, Zhang Z, Du G, Wan X. Acrp30 inhibits leptin-induced metastasis by downregulating the JAK/STAT3 pathway via AMPK activation in aggressive SPEC-2 endometrial cancer cells. Oncol Rep. 2012;27(5):1488-96.
- Liu L, Wang L, Zheng J, Tang G. Leptin promotes human endometrial carcinoma cell proliferation by enhancing aromatase (P450arom) expression and estradiol formation. Eur J Obstet Gynecol Reprod Biol. 2013;170(1):198-201. [DOI:10.1016/j.ejogrb.2013.04.004] [PMID]
- Bitton-Worms K, Rostoker R, Braun S, Shen-Orr Z, LeRoith D. The effect of leptin administration on mammary tumor growth in diabetic mice. Hormone and Metabolic Research. 2013;45(09):655-9. [DOI:10.1055/s-0033-1345151] [PMID]
- Cymbaluk A, Chudecka-Głaz A, Rzepka-Górska 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(1):74-7. [DOI:10.1016/j.ejogrb.2006.08.012] [PMID]
- Cymbaluk-Płoska A, Chudecka-Głaz A, Jagodzińska A, Pius-Sadowska E, Sompolska-Rzechuła A, Machaliński B, et al. Evaluation of biologically active substances promoting the development of or protecting against endometrial cancer. OncoTargets Ther. 2018;11:1363. [DOI:10.2147/OTT.S155942] [PMID] [PMCID]
- Wang P-P, He X-Y, Wang R, Wang Z, Wang Y-G. High leptin level is an independent risk factor of endometrial cancer: a meta-analysis. Cell Physiol Biochem. 2014;34(5):1477-84. [DOI:10.1159/000366352] [PMID]
- Zhou X, Li H, Chai Y, Liu Z. Leptin inhibits the apoptosis of endometrial carcinoma cells through activation of the nuclear factor κB-inducing kinase/IκB kinase pathway. Int J Gynecol Cancer. 2015;25(5). [DOI:10.1097/IGC.0000000000000440] [PMID]
- Wang J, Wieslander C, Hansen G, Cass I, Vasilev S, Holschneider CH. Thin endometrial echo complex on ultrasound does not reliably exclude type 2 endometrial cancers. Gynecol Oncol. 2006;101(1):120-5. [DOI:10.1016/j.ygyno.2005.09.042] [PMID]
- Méndez-López LF, Zavala-Pompa A, Cortés-Gutiérrez EI, Cerda-Flores RM, Davila-Rodriguez MI. Leptin receptor expression during the progression of endometrial carcinoma is correlated with estrogen and progesterone receptors. Arch Med Sci: AMS. 2017;13(1):228. [DOI:10.5114/aoms.2017.64721] [PMID] [PMCID]
- Özler A, Kuşçu NK, Temiz P, Kandiloğlu AR, Koyuncu FM. Leptin expression in proliferative, secretory and hyperplastic endometrial tissues. Turk Ger Gynecol Assoc. 2011;12(3):157. [DOI:10.5152/jtgga.2011.37] [PMID] [PMCID]
- Byrne FL, Martin AR, Kosasih M, Caruana BT, Farrell R. The role of hyperglycemia in endometrial cancer pathogenesis. Cancers. 2020;12(5):1191. [DOI:10.3390/cancers12051191] [PMID] [PMCID].
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