Article
Open Access
Looking for miRNA from plasma microvesicles differentially expressed in prostate tumors and healthy men
1 Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences, Novosibirsk 630090, Russia
2 E.N. Meshalkin National Medical Research Center of the Ministry of Health of the Russian Federation, Novosibirsk 630055, Russia
  • Volume
  • Citation
    Bryzgunova O, Yakovlev A, Ostaltsev I, Laktionov P, Konoshenko M. Looking for miRNA from plasma microvesicles differentially expressed in prostate tumors and healthy men. ExRNA 2024(2):0009, https://doi.org/10.55092/exrna20240009. 
  • DOI
    10.55092/exrna20240009
  • Copyright
    Copyright2024 by the authors. Published by ELSP.
Abstract

Aim: Current prostate cancer (PCa) diagnostics are based on PSA level assessment as well as histological analysis of biopsies. However, both false negative and false positive diagnoses are still made. Sensitive and specific markers of PCa are needed. In the present manuscript 14 different cell-free miRNAs were studied in blood plasma extracellular vehicles (EVs) of PCa and benign prostatic hyperplasia (BPH) patients as well as healthy donors. Materials and Methods: Plasma EVs isolation was performed by an aggregation-precipitation protocol. miRNA was isolated by the guanidine isothiocyanate/octanoic acid protocol. miRNAs expression was assessed by reverse transcription and quantitative PCR. Results: It was shown, that the expression of 2 miRNA ratios: miR-30e/miR-19b and miR-19b/miR-92a, differed between all groups. 8 miRNA ratios differentiated PCa patients and healthy donors, 15 ratios differentiated BPH and PCa patients, as well as BPH patients and healthy donors. 12 miRNA pairs aberrantly expressed in blood EVs of PCa and BPH patients were characterized by ddCt values over 1,0. Moreover, three of these miRNA ratios (miR-378a/miR-30e, miR-378a/miR-144, and miR-660/miR-19b) were characterized by high values of AUC (79%–82%), sensitivity (70%–78%) and specificity (63%–81%). Conclusion: The diagnostic characteristics of studied miRNA ratios indicate that they cannot be considered an independent and sufficient diagnostic marker but, quite likely, can be used as additional indicators if a diagnosis is needed to be clarified. Their potential as additional markers to PSA is substantiated by the lack of significant correlation between these markers.

Keywords

prostate cancer; miRNA; liquid biopsy; blood plasma; benign prostatic hyperplasia; extracellular vesicles

Preview
References
  • [1] Sung H, Ferlay J, Siegel R, Laversanne M, Soerjomataram I, et al. Global cancer statistics GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 2021, 71:209–249.
  • [2] Berry S, Coffey D, Walsh P, Ewing L. The development of human benign prostatic hyperplasia with age. J. Urol. 1984, 132:474–479.
  • [3] Paolone D. Benign prostatic hyperplasia. Clin. Geriatr. Med. 2010, 26:223–239.
  • [4] Omer A, Lamb A. Optimizing prostate biopsy techniques. Curr. Opin. Urol. 2019, 29:578–586.
  • [5] Serefoglu E, Altinova S, Ugras N, Akincioglu E, Asil E, et al. How reliable is 12-core prostate biopsy procedure in the detection of prostate cancer? Can. Urol. Assoc. J. 2013, 7:E293–298.
  • [6] Djavan B, Ravery V, Zlotta A, Dobronski P, Dobrovits M, et al. Prospective evaluation of prostate cancer detected on biopsies 1, 2, 3 and 4: when should we stop? J. Urol. 2001, 166:1679–1683.
  • [7] Tan N, Lane B, Li J, Moussa A, Soriano M, et al. Prostate cancers diagnosed at repeat biopsy are smaller and less likely to be high grade. J. Urol. 2008, 180:1325–1329.
  • [8] Beltran L, Ahmad AS, Sandu H, Kudahetti S, Soosay G, et al. Transatlantic Prostate Group. Histopathologic False-positive Diagnoses of Prostate Cancer in the Age of Immunohistochemistry. Am. J. Surg. Pathol. 2019, 43:361–36
  • [9] Uzuner E, Ulu G, Gürler S, Baran Y. The Role of MiRNA in Cancer: Pathogenesis, Diagnosis, and Treatment. Methods Mol. Biol. 2022, 2257:375–422.
  • [10] Shukla V, Adiga D, Jishnu P, Varghese V, Satyamoorthy K, et al. Role of miRNA clusters in epithelial to mesenchymal transition in cancer. Front. Biosci. (Elite Ed) 2020, 12:48–78.
  • [11] Moustafa A, Kim H, Albeltagy R, El-Habit O, Abdel-Mageed A. MicroRNAs in prostate cancer: From function to biomarker discovery. Exp. Biol. Med. 2008, 243:817–825.
  • [12] Xu R, Rai A, Chen M, Suwakulsiri W, Greening D, et al. Extracellular vesicles in cancer — implications for future improvements in cancer care. Nat. Rev. Clin. Oncol. 2018, 15:617–638.
  • [13] Akoto T, Saini S. Role of Exosomes in Prostate Cancer Metastasis. Int. J. Mol. Sci. 2021, 22:3528.
  • [14] Dong Q, Liu X, Cheng K, Sheng J, Kong J, et al. Pre-metastatic niche formation in different organs induced by tumor extracellular vesicles. Front. Cell Dev. Biol. 2021, 9:733627.
  • [15] Bryzgunova O, Zaporozhchenko I, Lekchnov E, Amelina E, Konoshenko M, et al. Data analysis algorithm for the development of extracellular miRNA-based diagnostic systems for prostate cancer. PLoS One 2019, 14:e0215003.
  • [16] Konoshenko M, Lekchnov E., Bryzgunova O, Zaporozhchenko I, Yarmoschuk S, et al. The Panel of 12 Cell-Free MicroRNAs as Potential Biomarkers in Prostate Neoplasms. Diagnostics 2020, 10:38.
  • [17] Jiang F, Liang Y, Wei W, Zou C, Chen G, et al. Functional classification of prostate cancerassociated miRNAs through CRISPR/Cas9mediated gene knockout. Mol. Med. Rep. 2020, 22:3777–3784.
  • [18] David MK, Leslie SW. Prostate Specific Antigen. 2022, In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing, 2024.
  • [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. Diagnostics (Basel) 2021, 11:384.
  • [20] Lekchnov E, Zaporozhchenko I, Morozkin E, Bryzgunova O, Vlassov V, et al. Protocol for miRNA isolation from biofluids. Anal. Biochem. 2016, 499:78–84.
  • [21] Chen C. Real-time quantification of microRNAs by stem-loop RT-PCR. Nucleic Acids Res. 2005, 33:e179.
  • [22] 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. U. S. A. 2011, 108:3713–3718.
  • [23] 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 Bioinform. 2015, 16:388.
  • [24] Lekchnov E, Amelina E, Bryzgunova O, Zaporozhchenko I, Konoshenko MY, et al. Searching for the Novel Specific Predictors of Prostate Cancer in Urine: The Analysis of 84 miRNA Expression. Int. J. Mol. Sci. 2018, 19:4088.
  • [25] Abudoubari S, Bu K, Mei Y, Maimaitiyiming A, An H, et al. Preliminary study on miRNA in prostate cancer. World J. Surg. Oncol. 2023, 21:270.
  • [26] 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, 21:2578.
  • [27] de Nóbrega M, Dos Reis M, Pereira É, de Souza M, de Syllos Cólus I. The potential of cell-free and exosomal microRNAs as biomarkers in liquid biopsy in patients with prostate cancer. J. Cancer Res. Clin. Oncol. 2022, 148:2893–2910.
  • [28] Joković SM, Dobrijević Z, Kotarac N, Filipović L, Popović M, et al. MiR-375 and miR-21 as Potential Biomarkers of Prostate Cancer: Comparison of Matching Samples of Plasma and Exosomes. Genes (Basel) 2022, 13:2320.
  • [29] Endzeliņš E, Berger A, Melne V, Bajo-Santos C, Soboļevska K, et al. Detection of circulating miRNAs: comparative analysis of extracellular vesicle-incorporated miRNAs and cell-free miRNAs in whole plasma of prostate cancer patients. BMC Cancer 2017, 17:730.
  • [30] Zhang N, Li Z, Bai F, Ji N, Zheng Y, et al. MicroRNA expression profiles in benign prostatic hyperplasia. Mol. Med. Rep. 2018, 17:3853–3858.
  • [31] Cochetti G, Poli G, Guelfi G, Boni A, Egidi M, et al. Different levels of serum microRNAs in prostate cancer and benign prostatic hyperplasia: evaluation of potential diagnostic and prognostic role. Onco. Targets Ther. 2016, 9:7545–7553.
  • [32] Alallam B, Choukaife H, Seyam S, Lim V, Alfatama M. Advanced Drug Delivery Systems for Renal Disorders. Gels 2023, 9(2):115.
  • [33] Lichtenstein A, Melkonyan H, Tomei L, Umansky S. Circulating nucleic acids and apoptosis. Ann. N. Y. Acad. Sci. 2001, 945:239–249.