Metabolik Sendrom ve Obezite Varlığında Prostat ile İlgili Belirteçlerin İncelenmesi: Tek Merkez Sonuçları

Öz

Amaç: Obezitenin ve metabolik sendromun prevalansı, dünya genelinde hızla yükselmektedir. Bu çalışmada obezite ve metabolik sendromu olan kişilerde prostat kanseri taramasında bir belirteç olarak kullanılan prostat spesifik antijen (PSA) ve türevlerinin nasıl değiştiğini incelemeyi amaçladık. Gereç ve Yöntemler: Araştırmaya Mayıs 2023 – Nisan 2024 tarihleri arasında Zonguldak Bülent Ecevit Hastanesi Endokrinoloji polikliniğinde obezite tanısı alan ve çalışma kriterlerini karşılayan 100 hasta ve 50 sağlıklı gönüllü dahil edildi. Hastalar metabolik sendromlu obezite ve metabolik sendromsuz obezite olmak üzere 2 gruba ayrıldı. Metabolik olarak sağlıklı olup olmadıklarını değerlendirmek amacıyla NCEP-ATP III metabolik sendrom tanı kriterleri kullanıldı. Bu kriterlere göre, beş kriterden herhangi üçünü karşılayan hastalar metabolik sendromlu obezite olarak kabul edilirken; bu kriterleri karşılamayan bireyler metabolik sendromsuz obezite kategorisinde değerlendirildi. Çalışma gruplarında PSA, freePSA ve proPSA düzeyleri bakılırken, %freePSA ve %proPSA düzeyleri hesaplandı. Bulgular: Obeziteli yaşayan hastaların total PSA, serbest PSA ve % free PSA düzeyleri kontrol grubundan farklı değildi (p>0.05). ProPSA düzeyleri obeziteli hastalarda, özellikle metabolik sendromsuz obezite hastalarında anlamlı derecede düşüktü (p=0.012), ancak %proPSA düzeylerinde herhangi bir fark gözlemlenmedi (p>0.05). ProPSA ile boy, vücut ağırlığı, VKİ, açlık kan şekeri, trigliserid ve HDL düzeyleri arasında bir korelasyon gözlenmedi. Sonuç: Daha düşük ProPSA konsantrasyonlarına rağmen %ProPSA'da değişiklik olmaması, ProPSA'daki azalmanın obeziteli hastalarda gözlenen toplam PSA'daki azalmaya orantılı bir yanıt olabileceğini düşündürmektedir. Ayrıca metabolik parametreler obezite ile ProPSA düzeyleri arasındaki ilişkiye katkıda bulunmamıştır. Bu özel popülasyonda ProPSA'nın tanısal faydasını ve klinik etkilerini değerlendirmek için daha fazla araştırmaya ihtiyaç vardır

Anahtar Kelimeler

• Obezite
• Metabolik sendrom
• Prostat spesifik antijen ve türevleri

Assessment of Prostate-Related Biomarkers in Individuals with Metabolic Syndrome and Obesity: A Single-Center Study

Abstract

Aim: The prevalence of obesity and metabolic syndrome is rapidly increasing worldwide. This study aimed to investigate the changes prostate-specific antigen (PSA) and its derivatives, commonly used as biomarkers in prostate cancer screening in individuals with obesity and metabolic syndrome. Material and Methods: The study included 100 patients diagnosed with obesity at the Endocrinology Clinic of Zonguldak Bulent Ecevit Hospital between May 2023 and April 2024, along with 50 healthy volunteers. The patients were divided into 2 groups: metabolic syndrome obesity and metabolic syndrome-free obesity. NCEP-ATP III metabolic syndrome diagnostic criteria were used to assess whether they were metabolically healthy. According to these criteria, patients who meet any three of the five criteria are considered to have metabolic syndrome obesity; individuals who did not meet these criteria were evaluated in the metabolic syndrome-free obesity category. PSA, free PSA and proPSA levels were analyzed, %freePSA and %proPSA values were calculated. Group comparisons were performed using the Kruskal–Wallis test, and correlations were assessed using Spearman’s rank correlation analysis. Results: Total PSA, free PSA and %freePSA levels were not difference in patients with obesity compared to the control group (p>0.05). ProPSA levels were significantly lower in patients with obesity, especially metabolic syndrome-free obesity (p=0.012), but no difference was observed in %proPSA levels (p>0.05). No correlation was observed between ProPSA and height, weight, BMI, fasting blood glucose, triglyceride and HDL-cholesterole levels. Conclusion: The lack of change in %ProPSA despite lower ProPSA concentrations suggests that the decrease in ProPSA may be a proportional response to the reduction in total PSA observed in individuals with obesity. This study provides novel evidence on the effect of obesity and metabolic phenotype on ProPSA levels in prostate-healthy individuals, a population that has been underrepresented in previous PSA-related research.

Keywords

• Obesity
• Metabolic syndrome
• Prostate specific antigen and its derivatives

References

1. 1. Albayrak AT, Serefoglu EC. Obesity and Men’s Health. Effects of Lifestyle on Men’s Health. Elsevier Inc.; 2019. 149–168.
2. 2. Hales CM, Carroll MD, Fryar CD, Ogden CL. Prevalence of Obesity Among Adults and Youth: United States, 2015-2016. NCHS Data Brief. 2017;288:1–8.
3. 3. Duncan DT, Wolin KY, Scharoun-Lee M, Ding EL, War ner ET, Bennett GG. Does perception equal reality? Weight misperception in relation to weight-related attitudes and be haviors among overweight and obese US adults. Int J Behav Nutr Phys Act. 2011;8:20.
4. 4. Gregory CO, Blanck HM, Gillespie C, Maynard LM, Serdula MK. Perceived health risk of excess body weight among over weight and obese men and women: differences by sex. Prev Med. 2008;47 (1):46–52.
5. 5. Ferlay J, Colombet M, Soerjomataram I, Mathers C, Parkin DM, Piñeros M, Znaor A, Bray F. Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods. Int J Cancer. 2019;144 (8):1941–53.
6. 6. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Can cers in 185 Countries. CA Cancer J Clin. 2021;71 (3):209–49.
7. 7. Saha A, Kolonin MG, DiGiovanni J. Obesity and prostate can cer- microenvironmental roles of adipose tissue. Nat Rev Urol. 2023;20 (10):579–96.
8. 8. Wilson RL, Taaffe DR, Newton RU, Hart NH, Lyons-Wall P, Galvão DA. Obesity and prostate cancer: A narrative review. Crit Rev Oncol Hematol. 2022;169:103543.

9. 9. Zheng X, Peng R, Xu H, Lin T, Qiu S, Wei Q, Lu Y, Ai J. The as sociation between metabolic status and risk of cancer among patients with obesity: metabolically healthy obesity vs. meta bolically unhealthy obesity. Front Nutr. 2022;9:783660.
10. 10. Wang J, Apizi A, Qiu H, Tao N, An H. Association between metabolic obesity phenotypes and the risk of developing pros tate cancer: a propensity score matching study based on Xinji ang. Front Endocrinol (Lausanne). 2024;15:1442740.
11. 11. Etzioni R, Tsodikov A, Mariotto A, Szabo A, Falcon S, We gelin J, diTommaso D, Karnofski K, Gulati R, Penson DF, Feuer E. Quantifying the role of PSA screening in the US pros tate cancer mortality decline. Cancer Causes Control. 2008;19 (2):175–81.
12. 12. Schröder FH, Hugosson J, Roobol MJ, Tammela TLJ, Zappa M, Nelen V, for the ERSPC Investigators. Screening and pros tate cancer mortality: results of the European Randomised Study of Screening for Prostate Cancer (ERSPC) at 13 years of follow-up. Lancet 2014;384 (9959):2027–35.
13. 13. Khan MA, Partin AW, Rittenhouse HG, Mikolajczyk SD, Sokoll LJ, Chan DW, Veltri RW. Evaluation of proprostate specific antigen for early detection of prostate cancer in men with a total prostate specific antigen range of 4.0 to 10.0 ng/ml. J Urol. 2003;170 (3):723–6.
14. 14. Shore ND, Pieczonka CM, Henderson RJ, Bailen JL, Saltzstein DR, Concepcion RS, Beebe-Dimmer JL, Ruterbusch JJ, Le TH, Levin RA, Wissmueller S, Prah P, Borotkanics R, Paivanas TA, van Breda A, Campbell DH, Walsh BJ. A comparison of pros tate health index, total PSA, %free PSA, and proPSA in a con temporary US population-The MiCheck-01 prospective trial. Urol Oncol. 2020;38 (8):683.e1-683.e10.
15. 15. Abrate A, Lazzeri M, Lughezzani G, Buffi N, Bini V, Haese A, de la Taille A, McNicholas T, Palou Redorta J, Gadda GM, Lista G, Kinzikeeva E, Fossati N, Larcher A, Dell’Oglio P, Mis tretta F, Freschi M, Guazzoni G. Clinical performance of the Prostate Health Index ( PHI ) for the prediction of prostate cancer in obese men: data from the PRO MEtheuS project, a multicentre E uropean prospective study. BJU Int. 2015;115 (4):537–45.
16. 16. Abrate A, Lazzeri M, Buffi N, Haese A, de la Taille A, McNich olas T, Palou Redorta J, Gadda GM, Lista G, Kinzikeeva E, Fossati N, Larcher A, Dell’Oglio P, Mistretta F, Freschi M, Guazzoni G. MP74-09: p2PSA and derivatives (%p2PSA and PHI) accurately predict prostate cancer in obese men from a multicenter prospective European study. J Urol. 2014 Apr;191 (4 Suppl):e2014.
17. 17. Sundaresan VM, Smani S, Rajwa P, Renzulli J, Sprenkle PC, Kim IY. Prostate-specific antigen screening for prostate can cer: diagnostic performance, clinical thresholds, and strategies for refinement. Urol Oncol. 2025;43 (1):41–8.
18. 18. Stamey TA, Kabalin JN, McNeal JE, Johnstone IM, Freiha F, Redwine EA. Prostate specific antigen in the diagnosis and treatment of adenocarcinoma of the prostate. II. Radical pros tatectomy treated patients. J Urol. 1989;141 (5):1076–83.
19. 19. Baillargeon J, Pollock BH, Kristal AR, Bradshaw P, Hernandez J, Basler J, Higgins B, Lynch S, Rozanski T, Troyer D, Thomp son I. The association of body mass index and prostate-spe cific antigen in a population-based study. Cancer. 2005;103 (5):1092–5.
20. 20. Fowke JH, Signorello LB, Chang SS, Matthews CE, Buchowski MS, Cookson MS, Clark PE, Blot WJ. Effects of obesity and height on prostate-specific antigen (PSA) and percentage of free PSA levels among African-American and Caucasian men. Cancer. 2006;107 (10):2361–7.
21. 21. Bañez LL, Hamilton RJ, Partin AW, Vollmer RT, Sun L, Ro driguez C, Wang Y, Terris MK, Aronson WJ, Presti JC Jr, Kane CJ, Amling CL, Moul JW, Freedland SJ. Obesity-relat ed plasma hemodilution and PSA concentration among men with prostate cancer. JAMA. 2007 Nov 21;298 (19):2275–80.
22. 22. Thompson IM, Leach R, Troyer D, Pollock B, Naylor S, Hig gins B. Relationship of body mass index and prostate specif ic antigen in a population-based study. Urol Oncol 2004;22 (2):127–31.
23. 23. Capitanio U, Perrotte P, Hutterer GC, Suardi N, Jeldres C, Shariat SF, Graefen M, Montorsi F, Karakiewicz PI. Effect of body mass index on prostate-specific antigen and percentage free prostate-specific antigen: results from a prostate cancer screening cohort of 1490 men. Int J Urol. 2009;16 (1):91–5.
24. 24. Sanchis-Bonet A, Morales-Palacios N, Barrionuevo-Gonzalez M, Ortega-Polledo LE, Ortiz-Vico FJ, Sanchez-Chapado M. Does obesity modify prostate cancer detection in a European cohort? Cent Eur J Urol. 2017;70 (1):30–6.
25. 25. Meunier ME, Neuzillet Y, Dreyfus JF, Schneider M, Rouprêt M, Cathelineau X, Kleinclauss F, Rozet F, Galiano M, Mongiat-Artus P. PSA and obesity among men with localized prostate cancer: results of the ANDROCAN study. World J Urol. 2021;39 (8):2945–51.
26. 26. Mikolajczyk SD, Marker KM, Millar LS, Kumar A, Saedi MS, Payne JK, Evans CL, Gasior GH, Linton HJ, Rittenhouse HG. A truncated precursor form of prostate-specific antigen is a more specific serum marker of prostate cancer. Cancer Res. 2001;61 (18):6958–63.
27. 27. Lazzeri M, Haese A, de la Taille A, Palou Redorta J, McNich olas T, Lughezzani G, Lista G, Buffi NM, Fossati N, Abrate A, Graefen M, Montorsi F, Guazzoni G, Karakiewicz PI. Serum isoform [-2]proPSA derivatives significantly improve predic tion of prostate cancer at initial biopsy in a total PSA range of 2–10 ng/mL: a multicentric European study. Eur Urol. 2013;63 (6):986–94.
28. 28. Catalona WJ, Partin AW, Sanda MG, Wei JT, Klee GG, Bang ma CH, Slawin KM, Marks LS, Loeb S, Broyles DL, Shin SS, Cruz AB, Chan DW, Sokoll LJ. A multicenter study of [-2] pro-prostate specific antigen combined with prostate specific antigen and free prostate specific antigen for prostate cancer detection in the 2.0 to 10.0 ng/mL prostate specific antigen range. J Urol. 2011;185 (5):1650–5
29. 29. Sokoll LJ, Chan DW, Mikolajczyk SD, Rittenhouse HG, Evans CL, Linton HJ, et al. Proenzyme psa for the early detection of prostate cancer in the 2.5-4.0 ng/ml total psa range: prelimi nary analysis. Urology 2003;61 (2):274–6.
30. 30. Zhu Y, Han CT, Zhang GM, Liu F, Ding Q, Xu JF. Effect of body mass index on the performance characteristics of PSA-related markers to detect prostate cancer. Sci Rep. 2016 Jan 12;6:19034.
31. 31. Abrate A, Lazzeri M, Buffi N, Haese A, de la Taille A, McNich olas T, Palou Redorta J, Gadda GM, Lista G, Kinzikeeva E, Fossati N, Larcher A, Dell’Oglio P, Mistretta F, Freschi M, Guazzoni G. Accuracy of p2PSA and derivatives (%p2PSA and PHI) in predicting prostate cancer in obese men from a multicenter European study. Eur Urol Suppl. 2014;13 (1):e341
32. 32. Stephan C, Vincendeau S, Houlgatte A, Cammann H, Jung K, Semjonow A. Multicenter Evaluation of [−2]Proprostate-Spe cific Antigen and the Prostate Health Index for Detecting Prostate Cancer. Clin Chem. 2013;59 (1):306–14.
33. 33. Jansen FH, van Schaik RHN, Kurstjens J, Horninger W, Klock er H, Bektic J, van der Poel HG, Bangma CH. Prostate-Specif ic Antigen (PSA) Isoform p2PSA in Combination with Total PSA and Free PSA Improves Diagnostic Accuracy in Prostate Cancer Detection. Eur Urol. 2010;57 (6):921–7.
34. 34. Wang W, Wang M, Wang L, Adams TS, Tian Y, Xu J. Diag nostic ability of %p2PSA and prostate health index for aggres sive prostate cancer: a meta-analysis. Sci Rep. 2014;4:5012.