Objective: The aim of the study was to demonstrate the diagnostic value of urinary high mobility group box 1 (HMGB1) level as a non-invasive tool that can be potentially used for diagnosis and during follow-up in patients with prostate cancer. Material and Methods: Forty-two patients with histopathologically confirmed prostate cancer from 40 to 75 years of age, 30 patients with an acute urinary tract infection (UTI) and 33 agematched healthy controls were enrolled in the study. Age, gender, body mass index (BMI) and urinary HMGB1 levels of the study groups were evaluated. The association of clinical features [prostate specific antigen (PSA), perineural invasion, Gleason score] with urinary HMGB1 levels was investigated in patients with prostate cancer. Results: While age and BMI were not different among the 3 groups (p=0.265 and p=0.254 respectively), PSA levels were significantly different (p<0.001). A significant difference was detected in urinary HMGB1 levels among the 3 groups (p<0.001). Additionally, a significant correlation was observed between Gleason scoring and urinary HMGB1 levels when compared among patients with low-, intermediate- and high-grade prostate cancer (p=0.003). Also, there was a significant difference in urinary HMGB1 levels between perineural invasion-positive and negative patients (p=0.04). Conclusion: Compared to control group, patients with a UTI and prostate cancer patients had higher HMGB1 levels. Urinary HMGB1 levels were much higher in prostate cancer patients than in controls. Urinary HMGB1 levels may be used as a noninvasive tool for diagnostic and screening purposes in prostate cancer patients in future controlled studies involving larger patient samples.
Keywords: Non-invasive screening test; prostate cancer; prostate cancer screening; urinary high mobility group box 1; tumor marker
Amaç: Çalışmanın amacı, prostat kanserli hastalarda tanı ve takip sırasında potansiyel olarak kullanılabilecek, invaziv olmayan bir araç olarak idrar yüksek hareketli grup proteini 1 [high mobility group box 1 (HMGB1)] düzeyinin tanısal değerini göstermektir. Gereç ve Yöntemler: Çalışmaya yaşları 40 ile 75 arasında değişen histopatolojik olarak doğrulanmış prostat kanseri olan 42 hasta, akut idrar yolu enfeksiyonu (İYE) olan 30 hasta ve yaşları eşleştirilmiş 33 sağlıklı kontrol dâhil edildi. Çalışma gruplarının yaş, cinsiyet, beden kitle indeksi (BKİ) ve idrar HMGB1 düzeyleri değerlendirildi. Prostat kanserli hastalarda klinik özelliklerin [prostat spesifik antijen (PSA), perinöral invazyon, Gleason skoru] idrar HMGB1 düzeyleri ile ilişkisi araştırıldı. Bulgular: Üç grup arasında yaş ve BKİ farklı değilken (sırasıyla p=0,265 ve p=0,254), PSA düzeyleri anlamlı derecede farklıydı (p<0,001). Üç grup arasında idrar HMGB1 düzeylerinde anlamlı fark tespit edildi (p<0,001). Ayrıca düşük, orta ve yüksek dereceli prostat kanserli hastalarla karşılaştırıldığında Gleason skorlaması ile idrar HMGB1 düzeyleri arasında anlamlı bir korelasyon gözlendi (p=0,003). Ayrıca perinöral invazyon pozitif ve negatif hastalar arasında idrar HMGB1 düzeyleri açısından anlamlı fark vardı (p=0,04). Sonuç: Kontrol grubuyla karşılaştırıldığında, İYE hastalarında ve prostat kanseri hastalarında HMGB1 düzeyleri daha yüksekti. İdrar HMGB1 seviyeleri prostat kanseri hastalarında kontrollere göre çok daha yüksekti. İdrar HMGB1 düzeyleri, daha büyük hasta örneklerini içeren gelecekteki kontrollü çalışmalarda prostat kanseri hastalarında tanı ve tarama amacıyla invaziv olmayan bir araç olarak kullanılabilir.
Anahtar Kelimeler: Noninvaziv tarama testi; prostat kanseri; prostat kanseri tarama; idrar yüksek hareketli grup proteini 1; tümör belirteci
- Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136(5):E359-86. [Crossref] [PubMed]
- Roberts MJ, Teloken P, Chambers SK, Sci B, Williams SG, Yaxley J, et al. Prostate Cancer Detection. Endotext [Internet]. MDText.com, Inc.; South Dartmouth (MA), 2018.
- Wolf AM, Wender RC, Etzioni RB, Thompson IM, D'Amico AV, Volk RJ, et al; American Cancer Society Prostate Cancer Advisory Committee. American Cancer Society guideline for the early detection of prostate cancer: update 2010. CA Cancer J Clin. 2010;60(2):70-98. [Crossref] [PubMed]
- Harvey CJ, Pilcher J, Richenberg J, Patel U, Frauscher F. Applications of transrectal ultrasound in prostate cancer. Br J Radiol. 2012;85 Spec No 1(Spec Iss 1):S3-17. [Crossref] [PubMed] [PMC]
- Litwin MS, Tan HJ. The diagnosis and treatment of prostate cancer: a review. JAMA. 2017;317(24):2532-42. [Crossref] [PubMed]
- Schröder FH, Hugosson J, Roobol MJ, Tammela TL, Ciatto S, Nelen V, et al; ERSPC Investigators. Screening and prostate-cancer mortality in a randomized European study. N Engl J Med. 2009;360(13):1320-8. [Crossref] [PubMed]
- Bustin M, Reeves R. High-mobility-group chromosomal proteins: architectural components that facilitate chromatin function. Prog Nucleic Acid Res Mol Biol. 1996;54:35-100. [Crossref] [PubMed]
- Stros M. HMGB proteins: interactions with DNA and chromatin. Biochim Biophys Acta. 2010;1799(1-2):101-13. [Crossref] [PubMed]
- Müller S, Ronfani L, Bianchi ME. Regulated expression and subcellular localization of HMGB1, a chromatin protein with a cytokine function. J Intern Med. 2004;255(3):332-43. [Crossref] [PubMed]
- Tang D, Kang R, Coyne CB, Zeh HJ, Lotze MT. PAMPs and DAMPs: signal 0s that spur autophagy and immunity. Immunol Rev. 2012;249(1):158-75. [Crossref] [PubMed] [PMC]
- Chen J, Xi B, Zhao Y, Yu Y, Zhang J, Wang C. High-mobility group protein B1 (HMGB1) is a novel biomarker for human ovarian cancer. Gynecol Oncol. 2012;126(1):109-17. Retraction in: Gynecol Oncol. 2015;138(3):764. [Crossref] [PubMed]
- Zhao CB, Bao JM, Lu YJ, Zhao T, Zhou XH, Zheng DY, et al. Co-expression of RAGE and HMGB1 is associated with cancer progression and poor patient outcome of prostate cancer. Am J Cancer Res. 2014;4(4):369-77. [PubMed] [PMC]
- Zumsteg ZS, Spratt DE, Pei I, Zhang Z, Yamada Y, Kollmeier M, et al. A new risk classification system for therapeutic decision making with intermediate-risk prostate cancer patients undergoing dose-escalated external-beam radiation therapy. Eur Urol. 2013;64(6):895-902. [Crossref] [PubMed]
- Todorova J, Pasheva E. High mobility group B1 protein interacts with its receptor RAGE in tumor cells but not in normal tissues. Oncol Lett. 2012;3(1):214-8. [Crossref] [PubMed] [PMC]
- Lv DJ, Song XL, Huang B, Yu YZ, Shu FP, Wang C, et al. HMGB1 promotes prostate cancer development and metastasis by interacting with brahma-related gene 1 and activating the akt signaling pathway. Theranostics. 2019;9(18):5166-82. [Crossref] [PubMed] [PMC]
- Leman ES, Madigan MC, Brünagel G, Takaha N, Coffey DS, Getzenberg RH. Nuclear matrix localization of high mobility group protein I(Y) in a transgenic mouse model for prostate cancer. J Cell Biochem. 2003;88(3):599-608. [Crossref] [PubMed]
- Nestl A, Von Stein OD, Zatloukal K, Thies WG, Herrlich P, Hofmann M, et al. Gene expression patterns associated with the metastatic phenotype in rodent and human tumors. Cancer Res. 2001;61(4):1569-77. [PubMed]
- Bussemakers MJ, van de Ven WJ, Debruyne FM, Schalken JA. Identification of high mobility group protein I(Y) as potential progression marker for prostate cancer by differential hybridization analysis. Cancer Res. 1991;51(2):606-11. [PubMed]
- Verrijdt G, Haelens A, Schoenmakers E, Rombauts W, Claessens F. Comparative analysis of the influence of the high-mobility group box 1 protein on DNA binding and transcriptional activation by the androgen, glucocorticoid, progesterone and mineralocorticoid receptors. Biochem J. 2002;361(Pt 1):97-103. [Crossref] [PubMed] [PMC]
- Findlay VJ, Turner DP, Yordy JS, McCarragher B, Shriver MR, Szalai G, et al. Prostate-derived ETS factor regulates epithelial-to-mesenchymal transition through both SLUG-dependent and independent mechanisms. Genes Cancer. 2011;2(2):120-9. [Crossref] [PubMed] [PMC]
- De Marzo AM, Platz EA, Sutcliffe S, Xu J, Grönberg H, Drake CG, et al. Inflammation in prostate carcinogenesis. Nat Rev Cancer. 2007;7(4):256-69. [Crossref] [PubMed] [PMC]
- Salagierski M, Schalken JA. Molecular diagnosis of prostate cancer: PCA3 and TMPRSS2:ERG gene fusion. J Urol. 2012;187(3):795-801. [Crossref] [PubMed]
- Roobol MJ, Haese A, Bjartell A. Tumour markers in prostate cancer III: biomarkers in urine. Acta Oncol. 2011;50 Suppl 1:85-9. [Crossref] [PubMed]
- Adachi J, Kumar C, Zhang Y, Olsen JV, Mann M. The human urinary proteome contains more than 1500 proteins, including a large proportion of membrane proteins. Genome Biol. 2006;7(9):R80. [Crossref] [PubMed] [PMC]
- Payne SR, Serth J, Schostak M, Kamradt J, Strauss A, Thelen P, et al. DNA methylation biomarkers of prostate cancer: confirmation of candidates and evidence urine is the most sensitive body fluid for non-invasive detection. Prostate. 2009;69(12):1257-69. [Crossref] [PubMed]
- Auprich M, Bjartell A, Chun FK, de la Taille A, Freedland SJ, Haese A, et al. Contemporary role of prostate cancer antigen 3 in the management of prostate cancer. Eur Urol. 2011;60(5):1045-54. [Crossref] [PubMed]
- Hessels D, Klein Gunnewiek JM, van Oort I, Karthaus HF, van Leenders GJ, van Balken B, et al. DD3(PCA3)-based molecular urine analysis for the diagnosis of prostate cancer. Eur Urol. 2003;44(1):8-15; discussion 15-6. [Crossref] [PubMed]
- Coley CM, Barry MJ, Fleming C, Wasson JH, Fahs MC, Oesterling JE. Should Medicare provide reimbursement for prostate-specific antigen testing for early detection of prostate cancer? Part II: Early detection strategies. Urology. 1995;46(2):125-41. [Crossref] [PubMed]
.: Process List