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Radikal Prostatektomi Uygulanan Prostat Kanseri Hastalarında Apelin'in Advers Histopatoloji ve Sağkalımla İlişkisi

Year 2025, Volume: 20 Issue: 2, 71 - 78, 29.06.2025

Hüseyin Özgür Kazan , Kenan Toprak , Burak Tüfekci , Samer Hussein Hadi Alhaddad , Ferruh Isman , Asıf Yıldırım

https://doi.org/10.33719/nju1603293

Abstract

Amaç: Prostat kanseri nedeniyle küratif radikal prostatektomi uygulanan hastalarda neoanjiyogenez, advers histopatoloji ve sağkalım ile ilişkili bir adipositokin olan Apelin arasındaki ilişki araştırılmıştır.
Yöntem: Bu prospektif kohort çalışmasında, Mart 2018 ile Ocak 2019 arasında küratif radikal prostatektomi geçiren 88 hasta çalışmaya dahil edildi. Androjen deprivasyon tedavisi veya radyoterapi dahil olmak üzere prostat kanseri için herhangi bir tedavi gören hastalar dışlandı. Çalışmada, radikal prostatektomi yapılmadan önce tüm hastaların serum örneklerindeki Apelin düzeyi ticari olarak temin edilebilen ELISA kitleri (Elabscience, Houston, TX, ABD) ile ölçüldü. Hastalar obez ve obez olmayan olmak üzere iki gruba ayrıldı ve iki grup sınır vücut kitle indeksi 30 kg/m2 olarak belirlendi. İki grup arasında hasta özellikleri, histopatolojik farklılıklar, prognoz ve Apelin düzeyleri değerlendirildi.
Bulgular: Çalışmada 17 hasta obez, 71 hasta obez değil; yaş, komorbidite indeksi, lipid parametreleri ve PSA düzeyleri benzerdi. Ortalama Apelin düzeyleri iki grup arasında farklı değildi (172,9'a karşı 146,4, p=0,262). Klinik progresyon(CP) oranı obez hastalarda daha yüksekti (%29,4'e karşı %2,8, p=0,001), biyokimyasal nüks oranları ise her iki grup arasında benzerdi.
Sonuç: Radikal prostatektomi sonrası CP riski obez hastalarda daha yüksekti ve bu hastaların Apelin düzeyleri lenf nodu invazyonu ile ilişkiliydi.

Keywords

Apelin Adipokin Biyokimyasal tekrarlama Klinik ilerleme Obezite Prostat kanseri

References

  • 1. Amin Al Olama A, Dadaev T, Hazelett DJ, et al. PRACTICAL Consortium; COGS-CRUK GWAS-ELLIPSE (Part of GAME-ON) Initiative; Australian Prostate Cancer BioResource; UK Genetic Prostate Cancer Study Collaborators; UK ProtecT Study Collaborators; Freedman M, Conti DV, Easton D, Coetzee GA, Eeles RA, Kote-Jarai Z. Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans. Hum Mol Genet. 2015;24(19):5589-602. https://doi.org/10.1093/hmg/ddv203
  • 2. Davies NM, Gaunt TR, Lewis SJ, et al. The effects of height and BMI on prostate cancer incidence and mortality: a Mendelian randomization study in 20,848 cases and 20,214 controls from the PRACTICAL consortium. Cancer Causes Control. 2015;26(11):1603-16. https://doi.org/10.1007/s10552-015-0654-9
  • 3. Vidal AC, Howard LE, Moreira DM, et al. Obesity increases the risk for high-grade prostate cancer: results from the REDUCE study. Cancer Epidemiol Biomarkers Prev. 2014;23(12):2936-42. https://doi.org/10.1158/1055-9965.EPI-14-0795
  • 4. Kang M, Byun SS, Lee SE, et al. Clinical Significance of Serum Adipokines according to Body Mass Index in Patients with Clinically Localized Prostate Cancer Undergoing Radical Prostatectomy. World J Mens Health. 2018;36(1):57-65. https://doi.org/10.5534/wjmh.17026
  • 5. Gimble JM. Adipose tissue-derived therapeutics. Expert Opin Biol Ther. 2003;3(5):705-13. https://doi.org/10.1517/14712598.3.5.705
  • 6. Tatemoto K, Hosoya M, Habata Y, et al. Isolation and Characterization of a Novel Endogenous Peptide Ligand for the Human APJ Receptor. Biochemical and Biophysical Research Communications [Internet]. 1998 Oct 20 [cited 2024;251(2):471-6. Available from: https://www.sciencedirect.com/science/article/pii/S0006291X9899489X
  • 7. Katugampola S, Davenport A. Emerging roles for orphan G-protein-coupled receptors in the cardiovascular system. Trends Pharmacol Sci. 2003;24(1):30-5. https://doi.org/10.1016/s0165-6147(02)00007-x
  • 8. Reaux A, De Mota N, Skultetyova I, et al. Physiological role of a novel neuropeptide, apelin, and its receptor in the rat brain. J Neurochem. 2001;77(4):1085-96. https://doi.org/10.1046/j.1471-4159.2001.00320.x
  • 9. Tang SY, Xie H, Yuan LQ, et al. Apelin stimulates proliferation and suppresses apoptosis of mouse osteoblastic cell line MC3T3-E1 via JNK and PI3-K/Akt signaling pathways. Peptides. 2007;28(3):708-18. https://doi.org/10.1016/j.peptides.2006.10.005
  • 10. Cayabyab M, Hinuma S, Farzan M, et al. Apelin, the natural ligand of the orphan seven-transmembrane receptor APJ, inhibits human immunodeficiency virus type 1 entry. J Virol. 2000;74(24):11972-6. https://doi.org/10.1128/jvi.74.24.11972-11976.2000
  • 11. Sorli SC, Le Gonidec S, Knibiehler B, et al. Apelin is a potent activator of tumour neoangiogenesis. Oncogene. 2007;26(55):7692-9. https://doi.org/10.1038/sj.onc.1210573
  • 12. Lacquaniti A, Altavilla G, Picone A, et al. Apelin beyond kidney failure and hyponatremia: a useful biomarker for cancer disease progression evaluation. Clin Exp Med. 2015 Feb;15(1):97-105. https://doi.org/10.1007/s10238-014-0272-y
  • 13. Tekin S, Sandal S, Colak C. Effects of Apelin-13 on Human Prostate Cancer Lines [Insan Prostat Kanseri Hucre Serilerinde Apelin-13’un Etkileri]. Med-Science [İnternet]. 2014;3(3):1427. [cited 2024 Oct 26] Available from: http://www.scopemed.org/fulltextpdf.php?mno=154668
  • 14. Wan Y, Zeng ZC, Xi M, 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. https://doi.org/10.1016/j.humpath.2014.10.027
  • 15. Berta J, Kenessey I, Dobos J, et al. Apelin expression in human non-small cell lung cancer: role in angiogenesis and prognosis. J Thorac Oncol. 2010;5(8):1120-9. https://doi.org/10.1097/JTO.0b013e3181e2c1ff
  • 16. Heo K, Kim YH, Sung HJ, Li HY, Yoo CW, Kim JY, Park JY, Lee UL, Nam BH, Kim EO, Kim SY, Lee SH, Park JB, Choi SW. Hypoxia-induced up-regulation of apelin is associated with a poor prognosis in oral squamous cell carcinoma patients. Oral Oncol. 2012;48(6):500-6. https://doi.org/10.1016/j.oraloncology.2011.12.015
  • 17. Berta J, Hoda MA, Laszlo V, et al. Apelin promotes lymphangiogenesis and lymph node metastasis. Oncotarget. 2014;5(12):4426-37. https://doi.org/10.18632/oncotarget.2032
  • 18. Baran M, Ozturk F, Canoz O, et al. The effects of apoptosis and apelin on lymph node metastasis in invasive breast carcinomas. Clin Exp Med. 2020;20(4):507-514. https://doi.org/10.1007/s10238-020-00635-2
  • 19. Rivera-Izquierdo M, Pérez de Rojas J, Martínez-Ruiz V, et al. Obesity as a Risk Factor for Prostate Cancer Mortality: A Systematic Review and Dose-Response Meta-Analysis of 280,199 Patients. Cancers (Basel). 2021;13(16):4169. https://doi.org/10.3390/cancers13164169
  • 20. Kim SJ, Park MU, Chae HK, et al. Overweight and obesity as risk factors for biochemical recurrence of prostate cancer after radical prostatectomy. Int J Clin Oncol. 2022;27(2):403-410. https://doi.org/10.1007/s10147-021-02058-9
  • 21. Chalfin HJ, Lee SB, Jeong BC, et al. Obesity and long-term survival after radical prostatectomy. J Urol. 2014;192(4):1100-4. https://doi.org/10.1016/j.juro.2014.04.086

Association of Apelin Levels with Lymph Node Invasion and Clinical Progression in Obese Patients Undergoing Radical Prostatectomy for Prostate Cancer

Year 2025, Volume: 20 Issue: 2, 71 - 78, 29.06.2025

Hüseyin Özgür Kazan , Kenan Toprak , Burak Tüfekci , Samer Hussein Hadi Alhaddad , Ferruh Isman , Asıf Yıldırım

https://doi.org/10.33719/nju1603293

Abstract

Objective: We aimed to determine the relationship between Apelin, an adipocytokine associated with neoangiogenesis, adverse histopathology such as extraprostatic extension, positive surgical margins, lymph node involvement, and high Gleason score, and survival in patients who underwent curative radical prostatectomy due to prostate cancer.
Material and Methods: In this prospective cohort study, 88 patients who underwent radical prostatectomy with curative intent between March 2018 and January 2019 were included. Patients with any treatment for prostate cancer, including androgen deprivation therapy or radiotherapy, were excluded. In the study, Apelin levels in the serum samples of all patients were measured with commercially available ELISA kits (Elabscience, Houston, TX, USA) before radical prostatectomy was performed. The patients were divided into two groups: non-obese and obese, with a BMI of 30 kg/m2 as the limit. Patient characteristics, histopathological differences, prognosis, and Apelin levels were evaluated between the two groups.
Results: In the study, 17 patients were obese, and 71 were non-obese; age, comorbidity index, lipid parameters, and PSA levels were similar. The mean Apelin levels were not different between the two groups (172.9 vs. 146.4, p=0.262). The clinical progression (CP) rate was higher in obese patients (29.4% vs. 2.8%, p=0.001), while the biochemical recurrence rates were similar between the groups. Higher Apelin levels were associated with lymph node invasion in obese patients (180.2 pN1 vs. 122.8 pN0, p=0.027), but this association was not observed in non-obese patients.
Conclusion: The risk of CP following radical prostatectomy was higher in obese patients, and Apelin levels were associated with lymph node invasion in these individuals.

Keywords

Apelin Adipokine Biochemical recurrence Clinical Progression Obesity Prostate cancer

Ethical Statement

Istanbul Medeniyet University Göztepe Training and Research Hospital Clinical Research Ethics Committee. Date/Protocol: 21.03.2018 Decision No: 2018/0080.

Supporting Institution

None.

References

  • 1. Amin Al Olama A, Dadaev T, Hazelett DJ, et al. PRACTICAL Consortium; COGS-CRUK GWAS-ELLIPSE (Part of GAME-ON) Initiative; Australian Prostate Cancer BioResource; UK Genetic Prostate Cancer Study Collaborators; UK ProtecT Study Collaborators; Freedman M, Conti DV, Easton D, Coetzee GA, Eeles RA, Kote-Jarai Z. Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans. Hum Mol Genet. 2015;24(19):5589-602. https://doi.org/10.1093/hmg/ddv203
  • 2. Davies NM, Gaunt TR, Lewis SJ, et al. The effects of height and BMI on prostate cancer incidence and mortality: a Mendelian randomization study in 20,848 cases and 20,214 controls from the PRACTICAL consortium. Cancer Causes Control. 2015;26(11):1603-16. https://doi.org/10.1007/s10552-015-0654-9
  • 3. Vidal AC, Howard LE, Moreira DM, et al. Obesity increases the risk for high-grade prostate cancer: results from the REDUCE study. Cancer Epidemiol Biomarkers Prev. 2014;23(12):2936-42. https://doi.org/10.1158/1055-9965.EPI-14-0795
  • 4. Kang M, Byun SS, Lee SE, et al. Clinical Significance of Serum Adipokines according to Body Mass Index in Patients with Clinically Localized Prostate Cancer Undergoing Radical Prostatectomy. World J Mens Health. 2018;36(1):57-65. https://doi.org/10.5534/wjmh.17026
  • 5. Gimble JM. Adipose tissue-derived therapeutics. Expert Opin Biol Ther. 2003;3(5):705-13. https://doi.org/10.1517/14712598.3.5.705
  • 6. Tatemoto K, Hosoya M, Habata Y, et al. Isolation and Characterization of a Novel Endogenous Peptide Ligand for the Human APJ Receptor. Biochemical and Biophysical Research Communications [Internet]. 1998 Oct 20 [cited 2024;251(2):471-6. Available from: https://www.sciencedirect.com/science/article/pii/S0006291X9899489X
  • 7. Katugampola S, Davenport A. Emerging roles for orphan G-protein-coupled receptors in the cardiovascular system. Trends Pharmacol Sci. 2003;24(1):30-5. https://doi.org/10.1016/s0165-6147(02)00007-x
  • 8. Reaux A, De Mota N, Skultetyova I, et al. Physiological role of a novel neuropeptide, apelin, and its receptor in the rat brain. J Neurochem. 2001;77(4):1085-96. https://doi.org/10.1046/j.1471-4159.2001.00320.x
  • 9. Tang SY, Xie H, Yuan LQ, et al. Apelin stimulates proliferation and suppresses apoptosis of mouse osteoblastic cell line MC3T3-E1 via JNK and PI3-K/Akt signaling pathways. Peptides. 2007;28(3):708-18. https://doi.org/10.1016/j.peptides.2006.10.005
  • 10. Cayabyab M, Hinuma S, Farzan M, et al. Apelin, the natural ligand of the orphan seven-transmembrane receptor APJ, inhibits human immunodeficiency virus type 1 entry. J Virol. 2000;74(24):11972-6. https://doi.org/10.1128/jvi.74.24.11972-11976.2000
  • 11. Sorli SC, Le Gonidec S, Knibiehler B, et al. Apelin is a potent activator of tumour neoangiogenesis. Oncogene. 2007;26(55):7692-9. https://doi.org/10.1038/sj.onc.1210573
  • 12. Lacquaniti A, Altavilla G, Picone A, et al. Apelin beyond kidney failure and hyponatremia: a useful biomarker for cancer disease progression evaluation. Clin Exp Med. 2015 Feb;15(1):97-105. https://doi.org/10.1007/s10238-014-0272-y
  • 13. Tekin S, Sandal S, Colak C. Effects of Apelin-13 on Human Prostate Cancer Lines [Insan Prostat Kanseri Hucre Serilerinde Apelin-13’un Etkileri]. Med-Science [İnternet]. 2014;3(3):1427. [cited 2024 Oct 26] Available from: http://www.scopemed.org/fulltextpdf.php?mno=154668
  • 14. Wan Y, Zeng ZC, Xi M, 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. https://doi.org/10.1016/j.humpath.2014.10.027
  • 15. Berta J, Kenessey I, Dobos J, et al. Apelin expression in human non-small cell lung cancer: role in angiogenesis and prognosis. J Thorac Oncol. 2010;5(8):1120-9. https://doi.org/10.1097/JTO.0b013e3181e2c1ff
  • 16. Heo K, Kim YH, Sung HJ, Li HY, Yoo CW, Kim JY, Park JY, Lee UL, Nam BH, Kim EO, Kim SY, Lee SH, Park JB, Choi SW. Hypoxia-induced up-regulation of apelin is associated with a poor prognosis in oral squamous cell carcinoma patients. Oral Oncol. 2012;48(6):500-6. https://doi.org/10.1016/j.oraloncology.2011.12.015
  • 17. Berta J, Hoda MA, Laszlo V, et al. Apelin promotes lymphangiogenesis and lymph node metastasis. Oncotarget. 2014;5(12):4426-37. https://doi.org/10.18632/oncotarget.2032
  • 18. Baran M, Ozturk F, Canoz O, et al. The effects of apoptosis and apelin on lymph node metastasis in invasive breast carcinomas. Clin Exp Med. 2020;20(4):507-514. https://doi.org/10.1007/s10238-020-00635-2
  • 19. Rivera-Izquierdo M, Pérez de Rojas J, Martínez-Ruiz V, et al. Obesity as a Risk Factor for Prostate Cancer Mortality: A Systematic Review and Dose-Response Meta-Analysis of 280,199 Patients. Cancers (Basel). 2021;13(16):4169. https://doi.org/10.3390/cancers13164169
  • 20. Kim SJ, Park MU, Chae HK, et al. Overweight and obesity as risk factors for biochemical recurrence of prostate cancer after radical prostatectomy. Int J Clin Oncol. 2022;27(2):403-410. https://doi.org/10.1007/s10147-021-02058-9
  • 21. Chalfin HJ, Lee SB, Jeong BC, et al. Obesity and long-term survival after radical prostatectomy. J Urol. 2014;192(4):1100-4. https://doi.org/10.1016/j.juro.2014.04.086
There are 21 citations in total.

Details

Primary Language English
Subjects Urology
Journal Section Research Article
Authors

Hüseyin Özgür Kazan 0000-0003-0202-0454

Kenan Toprak 0000-0002-8243-6777

Burak Tüfekci 0000-0002-7029-0109

Samer Hussein Hadi Alhaddad 0009-0006-7375-2352

Ferruh Isman 0000-0003-4278-4651

Asıf Yıldırım 0000-0002-3386-971X

Publication Date June 29, 2025
Submission Date December 24, 2024
Acceptance Date April 3, 2025
Published in Issue Year 2025 Volume: 20 Issue: 2

Cite

Vancouver Kazan HÖ, Toprak K, Tüfekci B, Alhaddad SHH, Isman F, Yıldırım A. Association of Apelin Levels with Lymph Node Invasion and Clinical Progression in Obese Patients Undergoing Radical Prostatectomy for Prostate Cancer. New J Urol. 2025;20(2):71-8.
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