Metabolic profile in patients with prostate cancer

Purpose of the study. To evaluate the levels of metabolic markers in patients with prostate cancer (PCa) in comparison with patients with benign prostatic hyperplasia (BPH).

Patients and methods. 108 patients were included in the study. The majority of patients had comorbidities: coronary heart disease, hypertension, and almost one third of patients had type 2 diabetes mellitus. Median (Me) age was 67 (64–74), body mass index was 25.9–34.7. The main study group included 54 patients with histologically verified prostate cancer, the comparison group consisted of 54 patients with benign prostatic hyperplasia (BPH). The level of basic biochemical parameters, glomerular filtration rate, lipidogram, total prostate-specific antigen (PSA), total testosterone was determined in all patients.

Results. When comparing anamnestic and biochemical parameters, the groups were not statistically significantly different. When comparing the groups by lipid status, it turned out that in the group with RPW, in contrast to the group of patients with BHP, statistically significantly higher levels of total cholesterol (5.13 (3.3–10,4) and 4.60 (2.5–6.3)) mmol/L, respectively, p = 0.023), low–density lipoproteins (2.93 (0.8–5.9) and 2.60 (0.9–4.2) mmol/L, respectively, p = 0.035), triglycerides (2.10 (1.0–8.0) and 1.70 (0.5–7.3) mmol/L, respectively, p = 0.048). In case of dyslipidemia, an increased risk of developing PCa was identified. Correlation analysis revealed a direct moderate relationship between total PSA levels and total cholesterol concentration (r = 0.51).

Conclusion. Our study revealed that in the PCa group, there was a higher level of total cholesterol, low-density lipoproteins, and triglycerides, in contrast to the group of patients with BPH. Additionally, in the group of patients with BPH, dyslipidemia was a risk factor in the development of PCa, which should be taken into account in PCa prevention and diagnosis.

1. Hryniewicz-Jankowska A, Augoff K, Sikorski AF. The role of cholesterol and cholesterol-driven membrane raft domains in prostate cancer. Exp Biol Med (Maywood). 2019 Oct;244(13):1053–1061. https://doi.org/10.1177/1535370219870771

2. Kaprin AD, Alekseev BIa, Matveev VB, Pushkar’ DIu, Govorov AV, Gorban’ NA, et al. Prostate cancer. Clinical recommendations. Journal of Modern Oncology. 2021;23(2):211–247. (In Russ.). https://doi.org/10.26442/18151434.2021.2.200959

3. Toivanen R, Shen MM. Prostate organogenesis: tissue inducti , hormonal regulati and cell type specifi ati . Development. 2017 Apr 15;144(8):1382–1398. https://doi.org/10.1242/dev.148270

4. Shatylko TV, Popkov VM, Korolev AYu, Fomkin RN, Krylova OV. Role of androgen receptors in pathogenesis of prostate cancer. Oncology Bulletin of the Volga region. 2018;2:18–23. (In Russ.).

5. Ryabova VM, Voskresenskiy MA, Popova BV. Role of the Tumor Suppressor RB in Development of Localized and Castration-Resistant Prostate Cancer. Cell and Tissue Biology. 2022;64(3):208–215. (In Russ.).

6. Huggins C, Hodges CV. Studies on prostatic cancer: I. The effect of castration, of estrogen and of androgen injection on serum phosphatases in metastatic carcinoma of the prostate. 1941. J Urol. 2002 Jul;168(1):9–12. https://doi.org/10.1016/s0022-5347(05)64820-3

7. Krakowsky Y, Morgentaler A. Risk of Testosterone Flare in the Era of the Saturation Model: One More Historical Myth. Eur Urol Focus. 2019 Jan;5(1):81–89. https://doi.org/10.1016/j.euf.2017.06.008

8. Faubert B, Solmonson A, DeBerardinis RJ. Metabolic reprogramming and cancer progression. Science. 2020 Apr 10;368(6487):eaaw5473. https://doi.org/10.1126/science.aaw5473

9. Sidaway P. Prostate cancer: Targeting lipid metabolism. Nat Rev Urol. 2017 Apr;14(4):196. https://doi.org/10.1038/nrurol.2017.28

10. Itkonen HM, Brown M, Urbanucci A, Tredwell G, Ho Lau C, Barfeld S, et al. Lipid degradation promotes prostate cancer cell survival. Oncotarget. 2017 Jun 13;8(24):38264–38275. https://doi.org/10.18632/oncotarget.16123

11. Peshkov MN, Peshkova GP, Reshetov IV. Metabolic changes in patients with prostate cancer with androgen deprivation therapy. Diabetes Mellitus. 2020;23(2):192–200. (In Russ.). https://doi.org/10.14341/dm10343

12. Osadchuk MA, Vasilieva IN, Kozlov VV, Mitrokhina OI. Metabolic syndrome as a risk factor for oncogenesis. Russian Journal of Preventive Medicine and Public Health. 2023;26(1):70–79. (In Russ.). https://doi.org/10.17116/profmed20232601170

13. Sun L, Parikh RB, Hubbard RA, Cashy J, Takvorian SU, Vaughn DJ, Robinson KW, Narayan V, Ky B. Assessment and Management of Cardiovascular Risk Factors Among US Veterans With Prostate Cancer. JAMA Netw Open. 2021 Feb 1;4(2):e210070. https://doi.org/10.1001/jamanetworkopen.2021.0070

14. Smirnov AV, Brusina EB, Magaryll YuA, Gordeeva LA. Epidemiological analysis of prostate cancer risk factors. Russian Journal of Preventive Medicine and Public Health. 2022;25(8):75 82. (In Russ.). https://doi.org/10.17116/profmed20222508175

15. Choi SYC, Ribeiro CF, Wang Y, Loda M, Plymate SR, Uo T. Druggable Metabolic Vulnerabilities Are Exposed and Masked during Progression to Castration Resistant Prostate Cancer. Biomolecules. 2022 Oct 28;12(11):1590. https://doi.org/10.3390/biom12111590

16. Lin C, Salzillo TC, Bader DA, Wilkenfeld SR, Awad D, Pulliam TL, et al. Prostate Cancer Energetics and Biosynthesis. Adv Exp Med Biol. 2019;1210:185–237. https://doi.org/10.1007/978-3-030-32656-2_10

17. Pelton K, Freeman MR, Solomon KR. Cholesterol and prostate cancer. Curr Opin Pharmacol. 2012 Dec;12(6):751–759. https://doi.org/10.1016/j.coph.2012.07.006

18. Galbraith L, Leung HY, Ahmad I. Lipid pathway deregulation in advanced prostate cancer. Pharmacol Res. 2018 May;131:177–184. https://doi.org/10.1016/j.phrs.2018.02.022

19. Allott EH, Masko EM, Freedland SJ. Obesity and prostate cancer: weighing the evidence. Eur Urol. 2013 May;63(5):800–809. https://doi.org/10.1016/j.eururo.2012.11.013

20. Di Francesco S, Robuffo I, Caruso M, Giambuzzi G, Ferri D, Militello A, Toniato E. Metabolic Alterations, Aggressive Hormone-Naïve Prostate Cancer and Cardiovascular Disease: A Complex Relationship. Medicina (Kaunas). 2019 Mar 7;55(3):62. https://doi.org/10.3390/medicina55030062

21. Todenhöfer T, Hennenlotter J, Kühs U, Gerber V, Gakis G, Vogel U, et al. Altered expression of farnesyl pyrophosphate synthase in prostate cancer: evidence for a role of the mevalonate pathway in disease progression? World J Urol. 2013 Apr;31(2):345–350. https://doi.org/10.1007/s00345-012-0844-y

22. Llaverias G, Danilo C, Wang Y, Witkiewicz AK, Daumer K, Lisanti MP, Frank PG. A Western-type diet accelerates tumor progression in an autochthonous mouse model of prostate cancer. Am J Pathol. 2010 Dec;177(6):3180–91. https://doi.org/10.2353/ajpath.2010.100568 Erratum in: Am J Pathol. 2011 Mar;178(3):1406.

23. Locke JA, Guns ES, Lehman ML, Ettinger S, Zoubeidi A, Lubik A, et al. Arachidonic acid activation of intratumoral steroid synthesis during prostate cancer progression to castration resistance. Prostate. 2010 Feb 15;70(3):239–251. https://doi.org/10.1002/pros.21057

24. Wang K, Gerke TA, Chen X, Prosperi M. Association of statin use with risk of Gleason score-specific prostate cancer: A hospital-based cohort study. Cancer Med. 2019 Dec;8(17):7399–7407. https://doi.org/10.1002/cam4.2500