https://doi.org/10.4081/aiua.2023.11610

Are elevated mitochondrial DNA fragments in prostatic inflammation a potential biomarker for prostate cancer?

Vol. 95 No. 3 (2023)
Submitted: July 26, 2023
Accepted: September 2, 2023
Published: September 27, 2023
Prostate, inflammation, cancer, mitochondrial DNA, post-prostatic massage
Abstract Views: 621
PDF: 382
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Authors

Ugur Aferin
Department of Urology, Medical Faculty, Demiroglu Bilim University, Istanbul, Turkey.
Nurten Bahtiyar
nurten.bahtiyar@iuc.edu.tr
https://orcid.org/0000-0003-2420-8415
Department of Biophysics, Cerrahpasa Medical Faculty, Istanbul University-Cerrahpasa, Istanbul, Turkey.
Ilhan Onaran
https://orcid.org/0000-0003-4630-9516
Department of Medical Biology, Cerrahpasa Medical Faculty, Istanbul University-Cerrahpasa, Istanbul, Turkey.
Hamdi Ozkara
Department of Urology, Cerrahpasa Medical Faculty, Istanbul University-Cerrahpasa, Istanbul, Turkey.

Background: We sought to determine whether two soluble forms with different size of mtDNA are linked to prostatic inflammation, and whether they discriminate prostate cancer (PCa) from inflammatory prostatic conditions. Methods: Histopathologically diagnosed prostatitis, PCa and benign prostatic hyperplasia patients (n = 93) were enrolled in this study and they were categorized as with and without prostate inflammation. Quantitative RT-PCR was used to analyze the levels of 79-bp and 230-bp fragments in urine and blood samples collected following prostate massage. Results: The urine mtDNA-79 and mtDNA-230 were significantly increased in patients with prostate inflammation compared with those in without inflammation. Here, 79-bp fragment of apoptotic origin was significantly higher level than 230-bp fragment of necrotic origin. Although mtDNA-79 copy number in serum samples was also increased in patients with prostate inflammation, mtDNA-230 was similar in the two groups. Furthermore, mtDNA-79 and mtDNA-230 copy numbers in postprostate massage urine were higher (about 16-fold and 22-fold, respectively) than those from serum samples. ROC analysis showed that, although post-prostate massage urine have relatively higher performance than blood, ability to discriminate cases of both fragments was not better than that of serum total PSA. Conclusions: Our results demonstrate that shorter cf-mtDNA fragment size in particular, increase in the presence of prostate inflammation in post-prostatic massage urine but both fragments could never improve serum total PSA performance.

Dimensions

Altmetric

PlumX Metrics

Downloads

Download data is not yet available.

Citations

Crossref
Scopus
Google Scholar
Europe PMC
Gui-Zhong L, Libo M, Guanglin H, Jianwei W. The correlation of extent and grade of inflammation with serum PSA levels in patients with IV prostatitis. Int Urol Nephrol. 2011;43(2):295-301. DOI: https://doi.org/10.1007/s11255-010-9825-5
MacLennan GT, Eisenberg R, Fleshman RL, et al. The influence of chronic inflammation in prostatic carcinogenesis: a 5-year followup study. J. Urol. 2006; 176(3): 1012-1016. DOI: https://doi.org/10.1016/j.juro.2006.04.033
Bergamini S, Bellei E, Bonetti LR, et al. Inflammation: an important parameter in the search of prostate cancer biomarkers. Proteome Sci 2014;12(1):1-12. DOI: https://doi.org/10.1186/1477-5956-12-32
Shu Y, Wu X, Tong X, et al. Circulating tumor DNA mutation profiling by targeted next generation sequencing provides guidance for personalized treatments in multiple cancer types. Sci. Rep. 2017;7(1):1-11. DOI: https://doi.org/10.1038/s41598-017-00520-1
Man SM, Kanneganti T-D. Converging roles of caspases in inflammasome activation, cell death and innate immunity. Nat. Rev. Immunol. 2016;16(1):7. DOI: https://doi.org/10.1038/nri.2015.7
McCully JD, Cowan DB, Pacak CA, Toumpoulis IK, Dayalan H, Levitsky S. Injection of isolated mitochondria during early reperfusion for cardioprotection. Am. J. Physiol. Heart Circ. Physiol. 2009;296(1):H94-H105. DOI: https://doi.org/10.1152/ajpheart.00567.2008
Zhang Q, Raoof M, Chen Y, et al. Circulating mitochondrial DAMPs cause inflammatory responses to injury. Nature. 2010;464(7285):104-107. DOI: https://doi.org/10.1038/nature08780
Klinman DM, Barnhart KM, Conover J. CpG motifs as immune adjuvants. Vaccine. 1999;17(1):19-25. DOI: https://doi.org/10.1016/S0264-410X(98)00151-0
Caielli S, Athale S, Domic B, et al. Oxidized mitochondrial nucleoids released by neutrophils drive type I interferon production in human lupus. J. Exp. Med. 2016;213(5):697-713. DOI: https://doi.org/10.1084/jem.20151876
Collins LV, Hajizadeh S, Holme E, Jonsson IM, Tarkowski A. Endogenously oxidized mitochondrial DNA induces in vivo and in vitro inflammatory responses. J. Leukoc. Biol. 2004;75(6):995-1000. DOI: https://doi.org/10.1189/jlb.0703328
Barbalat R, Ewald SE, Mouchess ML, Barton GM. Nucleic acid recognition by the innate immune system. Annu. Rev. Immunol. 2011;29:185-214. DOI: https://doi.org/10.1146/annurev-immunol-031210-101340
Zhang Q, Itagaki K, Hauser CJ. Mitochondrial DNA is released by shock and activates neutrophils via p38 map kinase. Shock. 2010;34(1):55-59. DOI: https://doi.org/10.1097/SHK.0b013e3181cd8c08
Yu M. Circulating cell-free mitochondrial DNA as a novel cancer biomarker: opportunities and challenges. Mitochondrial DNA. 2012;23(5):329-332. DOI: https://doi.org/10.3109/19401736.2012.696625
Ellinger J, Wittkamp V, Albers P, et al. Cell-free circulating DNA: diagnostic value in patients with testicular germ cell cancer. J. Urol. 2009;181(1):363-371. DOI: https://doi.org/10.1016/j.juro.2008.08.118
Ellinger J, Müller DC, Müller SC, Hauser S, Heukamp LC, von Ruecker A, Bastian PJ, Walgenbach-Brunagel G. Circulating mitochondrial DNA in serum: a universal diagnostic biomarker for patients with urological malignancies. Urol Oncol. 2012; 30(4):509-515. DOI: https://doi.org/10.1016/j.urolonc.2010.03.004
Herranz R, Oto J, Plana E, et al. Circulating Cell-Free DNA in Liquid Biopsies as Potential Biomarker for Bladder Cancer: A Systematic Review. Cancers. 2021;13(6):1448. DOI: https://doi.org/10.3390/cancers13061448
Budnik LT, Kloth S, Baur X, Preisser AM, Schwarzenbach H. Circulating mitochondrial DNA as biomarker linking environmental chemical exposure to early preclinical lesions elevation of mtDNA in human serum after exposure to carcinogenic halo-alkane-based pesticides. PloS one. 2013;8(5):e64413. DOI: https://doi.org/10.1371/journal.pone.0064413
Pisetsky DS. The origin and properties of extracellular DNA: from PAMP to DAMP. Clin. Immunol. 2012;144(1):32-40. DOI: https://doi.org/10.1016/j.clim.2012.04.006
Jahr S, Hentze H, Englisch S, et al. DNA fragments in the blood plasma of cancer patients: quantitations and evidence for their origin from apoptotic and necrotic cells. Cancer Res. 2001;61(4):1659-1665.
Nakahira K, Kyung S-Y, Rogers AJ, et al. Circulating mitochondrial DNA in patients in the ICU as a marker of mortality: derivation and validation. PLoS Med. 2013;10(12):e1001577. DOI: https://doi.org/10.1371/journal.pmed.1001577
Mehra N, Penning M, Maas J, van Daal N, Giles RH, Voest EE. Circulating mitochondrial nucleic acids have prognostic value for survival in patients with advanced prostate cancer. Clin. Cancer Res. 2007;13(2):421-426. DOI: https://doi.org/10.1158/1078-0432.CCR-06-1087
Zhou W, Zhu M, Gui M, et al. Peripheral blood mitochondrial DNA copy number is associated with prostate cancer risk and tumor burden. PloS one. 2014;9(10):e109470. DOI: https://doi.org/10.1371/journal.pone.0109470
Ellinger J, Müller SC, Wernert N, Von Ruecker A, Bastian PJ. Mitochondrial DNA in serum of patients with prostate cancer: a predictor of biochemical recurrence after prostatectomy. BJU Int. 2008;102(5):628-632. DOI: https://doi.org/10.1111/j.1464-410X.2008.07613.x
Deus CM, Tavares H, Beatriz M, Mota S, Lopes C. Mitochondrial Damage-Associated Molecular Patterns Content in Extracellular Vesicles Promotes Early Inflammation in Neurodegenerative Disorders. Cells. 2022 Aug 1;11(15):2364. DOI: https://doi.org/10.3390/cells11152364
Liu R, Xu F, Bi S, Zhao X, Jia B, Cen Y. Mitochondrial DNA-induced inflammatory responses and lung injury in thermal injury murine model: protective effect of cyclosporine-A. J Burn Care Res. 2019;40(3):355-360. DOI: https://doi.org/10.1093/jbcr/irz029
Aucamp J, Bronkhorst AJ, Badenhorst CP, Pretorius PJ. The diverse origins of circulating cell‐free DNA in the human body: a critical re‐evaluation of the literature. Biol. Rev. 2018;93(3):1649-1683. DOI: https://doi.org/10.1111/brv.12413

Supporting Agencies

Istanbul University-Cerrahpasa

How to Cite

Aferin, U., Bahtiyar, N., Onaran, I., & Ozkara, H. (2023). Are elevated mitochondrial DNA fragments in prostatic inflammation a potential biomarker for prostate cancer?. Archivio Italiano Di Urologia E Andrologia, 95(3). https://doi.org/10.4081/aiua.2023.11610
Copyright (c) 2023 the Author(s) Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

PAGEPress has chosen to apply the Creative Commons Attribution NonCommercial 4.0 International License (CC BY-NC 4.0) to all manuscripts to be published.