E-ISSN: 2619-9467

Contents    Cover    Publication Date: 06 Jun 2023
Year 2023 - Volume 33 - Issue 2

Open Access

Peer Reviewed

ORIGINAL RESEARCH
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Investigation of TRPM7 Immunoreactivity as a Biomarker to Predict Treatment-Resistant Endometrial Hyperplasia:A Retrospective Case-Control Study

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JCOG. 2023;33(2):59-65
DOI: 10.5336/jcog.2022-94838
Article Language: EN
Copyright Ⓒ 2024 by Türkiye Klinikleri. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
ABSTRACT
ABS TRACT Objective: In our study, we investigated transient receptor potential melastatin 7 (TRPM7) immunoreactivity in pre- and posttreatment pathology samples of patients with endometrial hyperplasia (EH) who responded to progesterone therapy and were resistant to progesterone therapy. Material and Methods: In this retrospective, comparative and single-center case-control study, endometrial tissue TRPM7 immunoreactivity was evaluated in sections obtained from paraffin blocks of 60 cases diagnosed with EH and proliferative endometrium. Randomly selected proliferative endometrium group for control [(Group(G)1, n=20)], The first [(G2, n=20)] and second [(G3, n=20)] biopsy results of the group diagnosed with EH and recovered with progesterone therapy. The first [(G4, n=20)] and second [(G5, n=20)] biopsy results of the group that was diagnosed with EH but did not recover with progesterone treatment. SPSS version 22 program (SPSS Inc., Chicago, IL) was used for statistical analysis. Intergroup evaluation was carried out with one-way ANOVA and post-hoc tukey test. p<0.05 values were considered statistically significant. Results: TRPM7 immunoreactivity was found to be significantly increased in G2, G4, and G5 compared to G1. However, no significant difference was observed between G2, G4, and G5. When compared with these groups, TRPM7 immunoreactivity was observed to be significantly decreased in G3, and it was observed to be similar to G1. Conclusion: In EH cases, the unchanged TRPM7 immunoreactivity before and after treatment may be an immunohistochemical biomarker for determining resistance to progesterone therapy.
REFERENCES:
  1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394-424. Erratum in: CA Cancer J Clin. 2020;70(4):313. [Crossref]  [PubMed] 
  2. Sanderson PA, Critchley HO, Williams AR, Arends MJ, Saunders PT. New concepts for an old problem: the diagnosis of endometrial hyperplasia. Hum Reprod Update. 2017;23(2):232-54. [PubMed]  [PMC] 
  3. Nees LK, Heublein S, Steinmacher S, Juhasz-Böss I, Brucker S, Tempfer CB, et al. Endometrial hyperplasia as a risk factor of endometrial cancer. Arch Gynecol Obstet. 2022;306(2):407-21. [Crossref]  [PubMed]  [PMC] 
  4. Kurman RJ, Kaminski PF, Norris HJ. The behavior of endometrial hyperplasia. A long-term study of "untreated" hyperplasia in 170 patients. Cancer. 1985;56(2):403-12. [Crossref]  [PubMed] 
  5. Kurman RJ, Norris HJ. Evaluation of criteria for distinguishing atypical endometrial hyperplasia from well-differentiated carcinoma. Cancer. 1982;49(12):2547-59. [Crossref]  [PubMed] 
  6. Gunderson CC, Fader AN, Carson KA, Bristow RE. Oncologic and reproductive outcomes with progestin therapy in women with endometrial hyperplasia and grade 1 adenocarcinoma: a systematic review. Gynecol Oncol. 2012;125(2):477-82. [Crossref]  [PubMed] 
  7. Guinamard R, Sallé L, Simard C. The non-selective monovalent cationic channels TRPM4 and TRPM5. Adv Exp Med Biol. 2011;704:147-71. [Crossref]  [PubMed] 
  8. Kraft R, Harteneck C. The mammalian melastatin-related transient receptor potential cation channels: an overview. Pflugers Arch. 2005;451(1):204-11. [Crossref]  [PubMed] 
  9. Everaerts W, Gevaert T, Nilius B, De Ridder D. On the origin of bladder sensing: Tr(i)ps in urology. Neurourol Urodyn. 2008;27(4):264-73. [Crossref]  [PubMed] 
  10. Yalçın E, Pala Ş, Atılgan R, Kuloğlu T, Önalan E, Artaş G, et al. Is there any difference between endometrial hyperplasia and endometrial carcinoma in terms of expression of TRPM2 and TRPM7 ion channels? Turk J Med Sci. 2019;49(2):653-60. [Crossref]  [PubMed]  [PMC] 
  11. Chandra V, Kim JJ, Benbrook DM, Dwivedi A, Rai R. Therapeutic options for management of endometrial hyperplasia. J Gynecol Oncol. 2016;27(1):e8. [Crossref]  [PubMed]  [PMC] 
  12. Gallos ID, Yap J, Rajkhowa M, Luesley DM, Coomarasamy A, Gupta JK. Regression, relapse, and live birth rates with fertility-sparing therapy for endometrial cancer and atypical complex endometrial hyperplasia: a systematic review and metaanalysis. Am J Obstet Gynecol. 2012;207(4):266.e1-12. [Crossref]  [PubMed] 
  13. Penner KR, Dorigo O, Aoyama C, Ostrzega N, Balzer BL, Rao J, et al. Predictors of resolution of complex atypical hyperplasia or grade 1 endometrial adenocarcinoma in premenopausal women treated with progestin therapy. Gynecol Oncol. 2012;124(3):542-8. [Crossref]  [PubMed] 
  14. Wei J, Zhang W, Feng L, Gao W. Comparison of fertility-sparing treatments in patients with early endometrial cancer and atypical complex hyperplasia: a meta-analysis and systematic review. Medicine (Baltimore). 2017;96(37):e8034. [Crossref]  [PubMed]  [PMC] 
  15. Duraiyan J, Govindarajan R, Kaliyappan K, Palanisamy M. Applications of immunohistochemistry. J Pharm Bioallied Sci. 2012;4(Suppl 2):S307-9. [Crossref]  [PubMed]  [PMC] 
  16. Travaglino A, Raffone A, Saccone G, Insabato L, Mollo A, De Placido G, et al. Immunohistochemical predictive markers of response to conservative treatment of endometrial hyperplasia and early endometrial cancer: a systematic review. Acta Obstet Gynecol Scand. 2019;98(9):1086-99. [Crossref]  [PubMed] 
  17. Capiod T. Cell proliferation, calcium influx and calcium channels. Biochimie. 2011;93(12):2075-9. [Crossref]  [PubMed] 
  18. Déliot N, Constantin B. Plasma membrane calcium channels in cancer: alterations and consequences for cell proliferation and migration. Biochim Biophys Acta. 2015;1848(10 Pt B):2512-22. [Crossref]  [PubMed] 
  19. De Clercq K, Held K, Van Bree R, Meuleman C, Peeraer K, Tomassetti C, et al. Functional expression of transient receptor potential channels in human endometrial stromal cells during the luteal phase of the menstrual cycle. Hum Reprod. 2015;30(6):1421-36. [Crossref]  [PubMed] 
  20. Ng NM, Jiang SP, Lv ZQ. Retrovirus-mediated siRNA targeting TRPM7 gene induces apoptosis in RBL-2H3 cells. Eur Rev Med Pharmacol Sci. 2012;16(9):1172-8. [PubMed] 
  21. Lam DH, Grant CE, Hill CE. Differential expression of TRPM7 in rat hepatoma and embryonic and adult hepatocytes. Can J Physiol Pharmacol. 2012;90(4):435-44. [Crossref]  [PubMed] 
  22. Neal AS, Nunez M, Lai T, Tosevska A, Morselli M, Amneus M, et al. Expression of stromal progesterone receptor and differential methylation patterns in the endometrium may correlate with response to progesterone therapy in endometrial complex atypical hyperplasia. Reprod Sci. 2020;27(9):1778-90. [Crossref]  [PubMed]  [PMC] 
  23. Chik F, Szyf M, Rabbani SA. Role of epigenetics in cancer initiation and progression. Adv Exp Med Biol. 2011;720:91-104. [Crossref]  [PubMed] 
  24. Clement NS, Oliver TR, Shiwani H, Sanner JR, Mulvaney CA, Atiomo W. Metformin for endometrial hyperplasia. Cochrane Database Syst Rev. 2017;10(10):CD012214. [Crossref]  [PubMed]  [PMC] 
  25. Tabrizi AD, Melli MS, Foroughi M, Ghojazadeh M, Bidadi S. Antiproliferative effect of metformin on the endometrium--a clinical trial. Asian Pac J Cancer Prev. 2014;15(23):10067-70. [Crossref]  [PubMed] 
  26. Ben Sahra I, Regazzetti C, Robert G, Laurent K, Le Marchand-Brustel Y, Auberger P, et al. Metformin, independent of AMPK, induces mTOR inhibition and cell-cycle arrest through REDD1. Cancer Res. 2011;71(13):4366-72. [Crossref]  [PubMed] 
  27. Liu M, Inoue K, Leng T, Guo S, Xiong ZG. TRPM7 channels regulate glioma stem cell through STAT3 and Notch signaling pathways. Cell Signal. 2014;26(12):2773-81. [Crossref]  [PubMed]  [PMC] 
  28. Luo Y, Wu JY, Lu MH, Shi Z, Na N, Di JM. Carvacrol alleviates prostate cancer cell proliferation, migration, and invasion through regulation of PI3K/Akt and MAPK signaling pathways. Oxid Med Cell Longev. 2016;2016:1469693. [Crossref]  [PubMed]  [PMC] 
  29. Devis-Jauregui L, Eritja N, Davis ML, Matias-Guiu X, Llobet-Navàs D. Autophagy in the physiological endometrium and cancer. Autophagy. 2021;17(5):1077-95. [Crossref]  [PubMed]  [PMC] 
  30. Zhao S, Li G, Yang L, Li L, Li H. Response-specific progestin resistance in a newly characterized Ishikawa human endometrial cancer subcell line resulting from long-term exposure to medroxyprogesterone acetate. Oncol Lett. 2013;5(1):139-44. [Crossref]  [PubMed]  [PMC] 
  31. Numata T, Sato-Numata K, Okada Y. TRPM7 is involved in acid-induced necrotic cell death in a manner sensitive to progesterone in human cervical cancer cells. Physiol Rep. 2019;7(13):e14157. [Crossref]  [PubMed]  [PMC] 
  32. Rybarczyk P, Gautier M, Hague F, Dhennin-Duthille I, Chatelain D, Kerr-Conte J, et al. Transient receptor potential melastatin-related 7 channel is overexpressed in human pancreatic ductal adenocarcinomas and regulates human pancreatic cancer cell migration. Int J Cancer. 2012;131(6):E851-61. [Crossref]  [PubMed] 
  33. Wang J, Liao QJ, Zhang Y, Zhou H, Luo CH, Tang J, et al. TRPM7 is required for ovarian cancer cell growth, migration and invasion. Biochem Biophys Res Commun. 2014;454(4):547-53. [Crossref]  [PubMed] 
  34. Sahni J, Scharenberg AM. TRPM7 ion channels are required for sustained phosphoinositide 3-kinase signaling in lymphocytes. Cell Metab. 2008;8(1):84-93. [Crossref]  [PubMed]  [PMC] 
  35. Inoue K, Xiong ZG. Silencing TRPM7 promotes growth/proliferation and nitric oxide production of vascular endothelial cells via the ERK pathway. Cardiovasc Res. 2009;83(3):547-57. [Crossref]  [PubMed]  [PMC]