Evaluation of Apelin/APJ and Fibronectin Expression in Genitourinary Tumors: An Immunohistochemical Analysis

Yıl 2023, , 566 - 572, 31.07.2023

Sevinç Şahin , Sema Avcı , Işıl Çiçekdağı , Ezgi Golal

https://doi.org/10.16899/jcm.1309615

Öz

Background/Aims: Cancer is a leading cause of death worldwide, making cancer research and the development of new treatment methods crucial. Bladder, endometrial, and prostate cancers are among the most prevalent forms of cancer. This study aimed to investigate the expression and distribution of endogenous apelin/APJ receptor and fibronectin in these genitourinary tumors and compare them to benign tissues to contribute new data to the literature.
Material and Method: Immunohistochemical methods were applied to 44 cases, including benign and malignant formalin-fixed paraffin-embedded tissues of the endometrium, prostate, and bladder.
Results: The findings showed a significant increase in apelin, APJ, and fibronectin expression in endometrioid adenocarcinoma, urothelial carcinoma, and prostatic adenocarcinoma compared to benign tissues. Moreover, the expression of these molecules had a direct correlation with each other in these tumors. However, in prostatic adenocarcinoma and endometrioid adenocarcinoma, as the tumor grade increased, the expression of these molecules decreased.
Conclusions: This is the first study to examine the co-expression and distribution of endogenous apelin/APJ receptors and fibronectin in genitourinary tumors and compare them histologically with benign counterparts, to the best of our knowledge. This underscores the novelty and significance of our findings, providing a foundation for further exploration of the potential roles of these molecules in tumorigenesis and cancer therapies.

Anahtar Kelimeler

Apelin, APJ, bladder carcinoma, endometrial carcinoma, fibronectin, genitourinary tumors, immunohistochemistry, prostate carcinoma

Destekleyen Kurum

none

Proje Numarası

none

Teşekkür

none

Genitoüriner Tümörlerde Apelin/APJ ve Fibronektin Ekspresyonunun Değerlendirilmesi: Bir İmmünohistokimyasal Analiz

Öz

Amaç: Kanser, dünya genelindeki ölüm nedenleri arasında önde gelen bir durum olup, kanser araştırmaları ve yeni tedavi yöntemlerinin geliştirilmesi ciddi önem arz etmektedir. Mesane, endometrium ve prostat kanserleri, en yaygın kanser türleri arasında yer almaktadır. Bu çalışma, bu genitouriner tümörlerdeki endojen apelin/APJ reseptörü ve fibronektin ekspresyonunu ve dağılımını araştırmayı ve elde ettiği verileri benign dokularla karşılaştırarak literatüre katkı sunmayı amaçlamıştır.
Gereç ve Yöntem: Endometrium, prostat ve mesaneye ait formalin ile fikse parafine gömülü benign ve malign dokularını içeren 44 vakaya immünohistokimyasal analiz uygulanmıştır. Bulgular: Endometrioid adenokarsinom, ürotelyal karsinom ve prostat adenokarsinomunda apelin, APJ ve fibronektin ekspresyonunda benign dokulara kıyasla önemli bir artış olduğu saptanmıştır. Ayrıca, bu tümörlerde bu moleküllerin ekspresyonu birbirleriyle doğrudan bir ilişki sergilemiştir. Bununla birlikte, prostat adenokarsinomunda ve endometrioid adenokarsinomunda tümör derecesi arttıkça, bu moleküllerin ekspresyonu azalmıştır.
Sonuç: Bu çalışma, literatürde genitouriner tümörlerdeki endojen apelin/APJ reseptörü ve fibronektin ekspresyonunun ve dağılımının histolojik olarak benign karşılıklarıyla kıyaslandığı ilk çalışmadır. Elde edilen bulguların, apelin/APJ reseptörü ve fibronektinin tümorigenez ve kanser tedavilerindeki potansiyel rolleri açısından planlanacak daha ileri araştırmalar için bir temel oluşturacağı kanısındayız.

Anahtar Kelimeler

Apelin, APJ, mesane karsinomu, endometrial karsinom, fibronektin, genitouriner tümörler, immünohistokimya, prostat karsinomu

Proje Numarası

none

Kaynakça

• 1. Fleshner NE. Genitourinary Cancer Prevention: Can We Make It a Reality? Eur Urol Focus. 2021;7(3):497-8.
• 2. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71(3):209-49.
• 3. Liu L, Yi X, Lu C, Wang Y, Xiao Q, Zhang L, et al. Study Progression of Apelin/APJ Signaling and Apela in Different Types of Cancer. Front Oncol. 2021;11:658253.
• 4. Lv SY, Yang YJ, Chen Q. Regulation of feeding behavior, gastrointestinal function and fluid homeostasis by apelin. Peptides. 2013;44:87-92.
• 5. Altinkaya SO, Nergiz S, Kucuk M, Yuksel H. Apelin levels are higher in obese patients with endometrial cancer. J Obstet Gynaecol Res. 2015;41(2):294-300.
• 6. Berta J, Kenessey I, Dobos J, Tovari J, Klepetko W, Jan Ankersmit H, et al. Apelin expression in human non-small cell lung cancer: role in angiogenesis and prognosis. J Thorac Oncol. 2010;5(8):1120-9.
• 7. Dupont J, Reverchon M, Cloix L, Froment P, Rame C. Involvement of adipokines, AMPK, PI3K and the PPAR signaling pathways in ovarian follicle development and cancer. Int J Dev Biol. 2012;56(10-12):959-67.
• 8. Patel SJ, Sanjana NE, Kishton RJ, Eidizadeh A, Vodnala SK, Cam M, et al. Identification of essential genes for cancer immunotherapy. Nature. 2017;548(7669):537-42.
• 9. Tolkach Y, Ellinger J, Kremer A, Esser L, Muller SC, Stephan C, et al. Apelin and apelin receptor expression in renal cell carcinoma. Br J Cancer. 2019;120(6):633-9.
• 10. Wan Y, Zeng ZC, Xi M, Wan S, Hua W, Liu YL, et al. Dysregulated microRNA-224/apelin axis associated with aggressive progression and poor prognosis in patients with prostate cancer. Hum Pathol. 2015;46(2):295-303.
• 11. Wysocka MB, Pietraszek-Gremplewicz K, Nowak D. The Role of Apelin in Cardiovascular Diseases, Obesity and Cancer. Front Physiol. 2018;9:557.
• 12. Yang Y, Lv SY, Ye W, Zhang L. Apelin/APJ system and cancer. Clin Chim Acta. 2016;457:112-6.
• 13. Patten J, Wang K. Fibronectin in development and wound healing. Adv Drug Deliv Rev. 2021;170:353-68.
• 14. Han Z, Lu ZR. Targeting Fibronectin for Cancer Imaging and Therapy. J Mater Chem B. 2017;5(4):639-54.
• 15. Lin TC, Yang CH, Cheng LH, Chang WT, Lin YR, Cheng HC. Fibronectin in Cancer: Friend or Foe. Cells. 2019;9(1).
• 16. Zhang HP, Zou J, Xu ZQ, Ruan J, Yang SD, Yin Y, et al. Association of leptin, visfatin, apelin, resistin and adiponectin with clear cell renal cell carcinoma. Oncol Lett. 2017;13(1):463-8.
• 17. Carattino MD, Prakasam HS, Ruiz WG, Clayton DR, McGuire M, Gallo LI, et al. Bladder filling and voiding affect umbrella cell tight junction organization and function. Am J Physiol Renal Physiol. 2013;305(8):F1158-68.
• 18. Soylu H, Unal B, Aksu K, Avci S, Caylan AE, Ustunel II. Evaluation of angiogenic apelin/apelin receptor axis in normal prostate, high grade prostatic intraepithelial neoplasia and prostatic adenocarcinoma. Malays J Pathol. 2022;44(3):461-7.
• 19. Wójcicka-Bartłomiejczyk B, Sikorski R, Wojcierowski J. [Fibronectin gene expression in preneoplastic states and female genital neoplasms]. Ginekol Pol. 1995;66(8):457-64.
• 20. Tekin S, Sandal S, Colak C. Effects of Apelin-13 on Human Prostate Cancer Lines. Medicine Science. 2014;3(3):1427-41.
• 21. Manaia JH, Cardoso GP, Babinski MA. Stereological evaluation of fibronectin in the periurethral region of the transitional zone from normal human prostates compared with benign prostatic hyperplasia. Int J Clin Exp Pathol. 2015;8(4):4143-7.
• 22. Aboseif S, El-Sakka A, Young P, Cunha G. Mesenchymal reprogramming of adult human epithelial differentiation. Differentiation. 1999;65(2):113-8.
• 23. Albrecht M, Renneberg H, Wennemuth G, Moschler O, Janssen M, Aumuller G, et al. Fibronectin in human prostatic cells in vivo and in vitro: expression, distribution, and pathological significance. Histochem Cell Biol. 1999;112(1):51-61.
• 24. Kolijn K, Verhoef EI, van Leenders GJ. Morphological and immunohistochemical identification of epithelial-to-mesenchymal transition in clinical prostate cancer. Oncotarget. 2015;6(27):24488-98.
• 25. Jia D, Entersz I, Butler C, Foty RA. Fibronectin matrix-mediated cohesion suppresses invasion of prostate cancer cells. BMC Cancer. 2012;12:94.
• 26. Arnold SA, Loomans HA, Ketova T, Andl CD, Clark PE, Zijlstra A. Urinary oncofetal ED-A fibronectin correlates with poor prognosis in patients with bladder cancer. Clin Exp Metastasis. 2016;33(1):29-44.
• 27. Di Maida F, Scalici Gesolfo C, Tellini R, Mari A, Sanfilippo C, Lambertini L, et al. Fibronectin urothelial gene expression as a new reliable biomarker for early detection of local toxicity secondary to adjuvant intravesical therapy for non-muscle invasive bladder cancer. Ther Adv Urol. 2021;13:1756287221995683.
• 28. Dong F, Shen Y, Xu T, Wang X, Gao F, Zhong S, et al. Effectiveness of urine fibronectin as a non-invasive diagnostic biomarker in bladder cancer patients: a systematic review and meta-analysis. World J Surg Oncol. 2018;16(1):61.
• 29. Futyma K, Kubiatowski T, Rozynska K, Zdunek M, Kotarski J, Rechberger T, et al. [Decreased osteonectin and fibronectin gene expression in endometrial cancer cancer as a prognostic marker]. Ginekol Pol. 2009;80(12):907-13.