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MiRNA expression in plasma extracellular vesicles of prostate cancer patients after radical prostatectomy
1 Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences, Novosibirsk, Russia
2 E.N. Meshalkin National Medical Research Center, Ministry of Health of the Russian Federation, Novosibirsk, Russia
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    Bryzgunova O, Yakovlev A, Ostaltsev I, Laktionov P, Konoshenko M. MiRNA expression in plasma extracellular vesicles of prostate cancer patients after radical prostatectomy. ExRNA 2024(3):0014, https://doi.org/10.55092/exrna20240014. 
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    Copyright2024 by the authors. Published by ELSP.
Abstract

Aim: Radical prostatectomy (RP) is the most frequent frontline PCa treatment. Biochemical recurrence (BCR) after radical prostatectomy occurs in 20%–40% of patients, but only 30% of these patients demonstrate cancer progression. Sensitive and specific markers of RP effectiveness are needed. Cell-free miRNAs from blood plasma packed in extracellular vesicles (EVs), namely the expression of 14 miRNAs before and one week after RP, were studied in comparison with their expression in EVs of benign prostatic hyperplasia patients and healthy donors in the present manuscript. Materials and Methods: Plasma EVs isolation was performed using an aggregation-precipitation protocol. MiRNA was isolated using the Guanidine isothiocyanate/Octanoic Acid Protocol. MiRNAs expression was assessed by reverse transcription and quantitative RT-PCR. Results: It was shown that 11 of the 72 studied miRNA ratios changed significantly after RP. Moreover, one of two miRNAs (miR-125b and miR-30e) took part in each miRNA ratio whose relative expression changed after RP. Conclusion: RP causes differential expression of plasma EVs miRNA. The obtained results indicate the prominent role of miR-125b and miR-30e in response to radical therapy. The study of miRNA expression in dynamics and in different biofluid fractions is required to assess the potential of extracellular miRNAs as sensitive biomarkers of therapy and to select their optimal source.

Keywords

prostate cancer; miRNA; liquid biopsy; blood plasma; prostatectomy; extracellular vesicles

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References
  • [1]Wang L, Lu B, He M, Wang Y, Wang Z, et al. Prostate Cancer Incidence and Mortality: Global Status and Temporal Trends in 89 Countries from 2000 to 2019. Front. Public Health 2022, 10:811044.
  • [2]Ellinger J, Alajati A, Kubatka P, Giordano F, Ritter M, et al. Prostate cancer treatment costs increase more rapidly than for any other cancer-how to reverse the trend? EPMA J. 2022, 13(1):1–7.
  • [3]Dell'Oglio P, Zaffuto E, Boehm K, Trudeau V, Larcher A, et al. Long-term survival of patients aged 80 years or older treated with radical prostatectomy for prostate cancer. Eur. J. Surg. Oncol. 2017, 43(8):1581–1588.
  • [4]Heidenreich A, Bastian P, Bellmunt J, Bolla M, Joniau S, et al. EAU guidelines on prostate cancer. Part 1: screening, diagnosis, and local treatment with curative intent-update 2013. Eur. Urol. 2013, 65(1):124–137.
  • [5]Han M, Partin A, Zahurak M, Piantadosi S, Epstein J, et al. Biochemical (prostate specific antigen) recurrence probability following radical prostatectomy for clinically localized prostate cancer. J. Urol. 2003, 169(2):517–523.
  • [6]Amling C, Blute M, Bergstralh E, Seay T, Slezak J, et al. Long-term hazard of progression after radical prostatectomy for clinically localized prostate cancer: continued risk of biochemical failure after 5 years. J. Urol. 2008, 164(1):101–105.
  • [7]Pound C, Partin A, Eisenberger M, Chan D, Pearson J, et al. Natural history of progression after PSA elevation following radical prostatectomy. Jama 1999, 281(17):1591–1597.
  • [8]Karakiewicz P, Eastham J, Graefen M, Cagiannos I, Stricker P, et al. Prognostic impact of positive surgical margins in surgically treated prostate cancer: multi-institutional assessment of 5831 patients. Urol. 2005, 66(6):1245–1250.
  • [9]Silberstein J, Eastham J. Significance and management of positive surgical margins at the time of radical prostatectomy. Indian J. Urol. 2014, 30(4):423–428.
  • [10]Paller C, Antonarakis E. Management of biochemically recurrent prostate cancer after local therapy: evolving standards of care and new directions. Clin. Adv. Hematol. Oncol. 2013, 11(1):14–23.
  • [11]Solovov V, Orlov A, Wosdwichenskij M, Fesenko D, Matyash Ya, et al. High-intensity focused ultrasound ablation (HIFU) for prostate cancer in 976 patients: 7-year results. Proceedings of the Samara Scientific Center of the Russian Academy of Sciences. 2015, 2(3):682–685. Available: 2015_2_682_685.pdf (smr.ru) (In Russian)
  • [12]Kucera R, Pecen L, Topolcan O, Dahal AR, Costigliola V, et al. Prostate cancer management: long-term beliefs, epidemic developments in the early twenty-first century and 3PM dimensional solutions. EPMA J. 2020, 11:399–418.
  • [13]Novara G, Ficarra V, Mocellin S, Ahlering T, Carroll P, et al. Systematic review and meta-analysis of studies reporting oncologic outcome after robot-assisted radical prostatectomy. Eur. Urol. 2012, 62(3):382–404.
  • [14]Guercio C, Mehta A. Predictors of Patient and Partner Satisfaction Following Radical Prostatectomy. Sex. Med. Rev. 2018, 6(2):295–301.
  • [15]Konoshenko M, Laktionov P. MiRNAs and radical prostatectomy: Current data, bioinformatic analysis and utility as predictors of tumour relapse. Andrology 2021, 9(4):1092–1107.
  • [16]Lieb V, Weigelt K, Scheinost L, Fischer K, Greither T, et al. Serum levels of miR-320 family members are associated with clinical parameters and diagnosis in prostate cancer patients. Oncotarget 2017. 9(12):10402.
  • [17]Al-Qatati A, Akrong C, Stevic I, Pantel K, Awe J, et al. Plasma microRNA signature is associated with risk stratification in prostate cancer patients. Int. J. Cancer 2017, 141(6):1231–1239.
  • [18]Konoshenko M, Bryzgunova O, Lekchnov E, Amelina E, Yarmoschuk S, et al. The Influence of Radical Prostatectomy on the Expression of Cell-Free MiRNA. Diagn. 2020, 10(8):600.
  • [19]Konoshenko M, Lekchnov E, Bryzgunova O, Kiseleva E, Pyshnaya I, et al. Isolation of Extracellular Vesicles from Biological Fluids via the Aggregation-Precipitation Approach for Downstream miRNAs Detection. Diagn. 2021, 11(3):384.
  • [20]Lekchnov E, Amelina E, Bryzgunova O, Zaporozhchenko I, Konoshenko M, et al. Searching for the Novel Specific Predictors of Prostate Cancer in Urine: The Analysis of 84 miRNA Expression. Int. J. Mol. Sci. 2018, 19(12):4088.
  • [21]Abudoubari S, Bu K, Mei Y, Maimaitiyiming A, An H, et al. Preliminary study on miRNA in prostate cancer. World J. Surg. Oncol. 2023, 21(1):270.
  • [22]Kooshkaki O, Rezaei Z, Rahmati M, Vahedi P, Derakhshani A, et al. MiR-144: A New Possible Therapeutic Target and Diagnostic/Prognostic Tool in Cancers. Int. J. Mol. Sci. 2020, 21(7):2578.
  • [23]Welsh JA, Goberdhan DCI, O'Driscoll L, Buzas EI, Blenkiron C, et al. Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches. J. Extracell. Vesicles 2024, 13(2):e12404.
  • [24]Chen C, Ridzon D, Broomer A, Zhou Z, Lee D, et al. Real-time quantification of microRNAs by stem-loop RT-PCR. Nucleic. Acids. Res. 2005, 33(20):e179.
  • [25]Boeri M, Verri C, Conte D, Roz L, Modena P, et al. MicroRNA signatures in tissues and plasma predict development and prognosis of computed tomography detected lung cancer. Proc. Natl. Acad. Sci. 2011, 108(9):3713–3718.
  • [26]Landoni E, Miceli R, Callari M, Tiberio P, Appierto V, et al. Proposal of supervised data analysis strategy of plasma miRNAs from hybridisation array data with an application to assess hemolysis-related deregulation. BMC Bioinf. 2015, 16: 1–10.
  • [27]Han M, Partin A, Zahurak M, Piantadosi S, Epstein J, et al. Biochemical (prostate specific antigen) recurrence probability following radical prostatectomy for clinically localized prostate cancer. J. Urol. 2003, 169(2):517–523.
  • [28]Amling C, Blute M, Bergstralh E, Seay T, Slezak J, et al. Long-term hazard of progression after radical prostatectomy for clinically localized prostate cancer: continued risk of biochemical failure after 5 years. J. Urol. 2008, 164(1):101–105.
  • [29]Dwivedi S, Pareek P, Vishnoi J, Sharma P, Misra S. Downregulation of miRNA-21 and cancer stem cells after chemotherapy results in better outcome in breast cancer patients. World J. of stem cells 2022, 14(4):310–313.
  • [30]Kim CH, Kim HK, Rettig RL, Kim J, Lee ET, et al. miRNA signature associated with outcome of gastric cancer patients following chemotherapy. BMC Med. Genomics 2011, 4:1–14.
  • [31]Wu P, Li D, Zhang C, Dai B, Tang X, et al. A unique circulating microRNA pairs signature serves as a superior tool for early diagnosis of pan-cancer. Cancer Lett. 2024, 588:216655.
  • [32]Fernandez N, Chavarriaga J, Ayala P, Pedraza A, Bolivar J, et al. MicroRNAs as Potential Liquid Biopsy Biomarker for Patients with Castration-Resistant Prostate Cancer. Res. Rep. Urol. 2022, 14:63–70.
  • [33]McDonald A, Raman J, Shen J, Liao J, Pandya B, et al. Circulating microRNAs in plasma before and after radical prostatectomy. Urol. Oncol. 2019, 37(11):814.e1–814.e7.
  • [34] Giangreco A, Vaishnav A, Wagner D, Finelli A, Fleshner N, et al. Tumor suppressor microRNAs, miR-100 and -125b, are regulated by 1,25-dihydroxyvitamin D in primary prostate cells and in patient tissue. Cancer Prev. Res. 2013, 6(5):483–494.
  • [35]Budd W, Seashols-Williams S, Clark G, Weaver D, Calvert V, et al. Dual Action of miR-125b as a Tumor Suppressor and OncomiR-22 Promotes Prostate Cancer Tumorigenesis. PLoS One 2015, 10(11):e0142373.
  • [36]Amir S, Ma A, Shi X, Xue L, Kung H, et al. OncomirmiR-125b suppresses p14ARF to modulate p53- dependent and p53-independent apoptosis in prostate cancer. PLoS One 2013, 8(4):e61064.
  • [37]Shi X, Xue L, Yang J, Ma A, Zhao J, et al. An androgen-regulated miRNA suppresses Bak1 expression and induces androgen-independent growth of prostate cancer cells. Proc. Natl. Acad. Sci. USA 2007, 104:19983–19988.
  • [38]DeVere White R, Vinall R, Tepper C, Shi X. MicroRNAs and their potential for translation in prostate cancer. Urol. Oncol. 2009, 27(3):307–311.
  • [39]Rana S, Valbuena GN, Curry E, Bevan CL, Keun HC. MicroRNAs as biomarkers for prostate cancer prognosis: a systematic review and a systematic reanalysis of public data. Br. J. Cancer 2022, 126(3):502–513.
  • [40]Jain G, Das P, Ranjan P, Neha, Valderrama F and Cieza-Borrella C. Urinary extracellular vesicles miRNA—A new era of prostate cancer biomarkers. Front. Genet. 2023, 14:1065757.