Influential Factors on Urine EV DNA Methylation Detection and Its Diagnostic Potential in Prostate Cancer

Overview

Journal Front Genet

Date 2024 Mar 5

PMID 38440192

Authors

Ting Ding

Yanjun Diao

Xianfei Zeng

Lei Zhou

Guojun Wu

Jiayun Liu

Xiaoke Hao

Affiliations

Soon will be listed here.

Abstract

The value of Extracellular vesicles (EVs) diagnostic markers is widely recognized. However, current research on EV DNA remains limited. This study investigates the biological properties, preprocessing factors, and diagnostic potential of EV DNA. We found that DNA positive vesicles account for 23.3% ± 6.7% of the urine total EV, with a large amount of DNA attached to the outside. EV DNA fragments are large, there is no significant effect on uEV DNA when store urine less than 6 h at 4°C. In addition, the influence of different EV extraction methods on methylation detection is also minor. More importantly, RASSF1A methylation in urine total EV DNA can distinguish between PCa and BPH, with an AUC of 0.874. Our results suggest the potential of urine EV DNA as a novel marker for PCa diagnosis. This provides a new idea for the study of urinary tumor markers.

Citing Articles

The detection, biological function, and liquid biopsy application of extracellular vesicle-associated DNA.

Guo S, Wang X, Shan D, Xiao Y, Ju L, Zhang Y Biomark Res. 2024; 12(1):123.

PMID: 39402599 PMC: 11476736. DOI: 10.1186/s40364-024-00661-2.

DNA methylation in human diseases.

Younesian S, Mohammadi M, Younesian O, Momeny M, Ghaffari S, Bashash D Heliyon. 2024; 10(11):e32366.

PMID: 38933971 PMC: 11200359. DOI: 10.1016/j.heliyon.2024.e32366.

References

Stam J, Bartel S, Bischoff R, Wolters J . Isolation of extracellular vesicles with combined enrichment methods. J Chromatogr B Analyt Technol Biomed Life Sci. 2021; 1169:122604. DOI: 10.1016/j.jchromb.2021.122604. View

Pan J, Chen J, Zhang B, Chen X, Huang B, Zhuang J . Association between RASSF1A promoter methylation and prostate cancer: a systematic review and meta-analysis. PLoS One. 2013; 8(9):e75283. PMC: 3779179. DOI: 10.1371/journal.pone.0075283. View

Yu L, Sui B, Fan W, Lei L, Zhou L, Yang L . Exosomes derived from osteogenic tumor activate osteoclast differentiation and concurrently inhibit osteogenesis by transferring COL1A1-targeting miRNA-92a-1-5p. J Extracell Vesicles. 2021; 10(3):e12056. PMC: 7812369. DOI: 10.1002/jev2.12056. View

Louie K, Seigneurin A, Cathcart P, Sasieni P . Do prostate cancer risk models improve the predictive accuracy of PSA screening? A meta-analysis. Ann Oncol. 2014; 26(5):848-864. DOI: 10.1093/annonc/mdu525. View

Pascual J, Attard G, Bidard F, Curigliano G, De Mattos-Arruda L, Diehn M . ESMO recommendations on the use of circulating tumour DNA assays for patients with cancer: a report from the ESMO Precision Medicine Working Group. Ann Oncol. 2022; 33(8):750-768. DOI: 10.1016/j.annonc.2022.05.520. View

Hagey D, Kordes M, Gorgens A, Mowoe M, Nordin J, Moro C . Extracellular vesicles are the primary source of blood-borne tumour-derived mutant KRAS DNA early in pancreatic cancer. J Extracell Vesicles. 2021; 10(12):e12142. PMC: 8485184. DOI: 10.1002/jev2.12142. View

Thakur B, Zhang H, Becker A, Matei I, Huang Y, Costa-Silva B . Double-stranded DNA in exosomes: a novel biomarker in cancer detection. Cell Res. 2014; 24(6):766-9. PMC: 4042169. DOI: 10.1038/cr.2014.44. View

Bernardino R, Leao R, Henrique R, Pinheiro L, Kumar P, Suravajhala P . Extracellular Vesicle Proteome in Prostate Cancer: A Comparative Analysis of Mass Spectrometry Studies. Int J Mol Sci. 2021; 22(24). PMC: 8707426. DOI: 10.3390/ijms222413605. View

Wang Y, Shi T, Srivastava S, Kagan J, Liu T, Rodland K . Proteomic Analysis of Exosomes for Discovery of Protein Biomarkers for Prostate and Bladder Cancer. Cancers (Basel). 2020; 12(9). PMC: 7564640. DOI: 10.3390/cancers12092335. View

10.

Diao Y, Zhu B, Ding T, Li R, Li J, Yang L . Tumor-derived extracellular vesicle nucleic acids as promising diagnostic biomarkers for prostate cancer. Front Oncol. 2023; 13:1201554. PMC: 10338955. DOI: 10.3389/fonc.2023.1201554. View

11.

Connell S, Yazbek-Hanna M, McCarthy F, Hurst R, Webb M, Curley H . A four-group urine risk classifier for predicting outcomes in patients with prostate cancer. BJU Int. 2019; 124(4):609-620. PMC: 6851983. DOI: 10.1111/bju.14811. View

12.

Robinson H, Roberts M, Gardiner R, Hill M . Extracellular vesicles for precision medicine in prostate cancer - Is it ready for clinical translation?. Semin Cancer Biol. 2023; 89:18-29. DOI: 10.1016/j.semcancer.2023.01.003. View

13.

Maire C, Fuh M, Kaulich K, Fita K, Stevic I, Heiland D . Genome-wide methylation profiling of glioblastoma cell-derived extracellular vesicle DNA allows tumor classification. Neuro Oncol. 2021; 23(7):1087-1099. PMC: 8673443. DOI: 10.1093/neuonc/noab012. View

14.

Vagner T, Spinelli C, Minciacchi V, Balaj L, Zandian M, Conley A . Large extracellular vesicles carry most of the tumour DNA circulating in prostate cancer patient plasma. J Extracell Vesicles. 2018; 7(1):1505403. PMC: 6084494. DOI: 10.1080/20013078.2018.1505403. View

15.

Elzanowska J, Semira C, Costa-Silva B . DNA in extracellular vesicles: biological and clinical aspects. Mol Oncol. 2020; 15(6):1701-1714. PMC: 8169445. DOI: 10.1002/1878-0261.12777. View

16.

Liu H, Tian Y, Xue C, Niu Q, Chen C, Yan X . Analysis of extracellular vesicle DNA at the single-vesicle level by nano-flow cytometry. J Extracell Vesicles. 2022; 11(4):e12206. PMC: 8977970. DOI: 10.1002/jev2.12206. View

17.

Sedej I, Stalekar M, Znidaric M, Goricar K, Kojc N, Kogovsek P . Extracellular vesicle-bound DNA in urine is indicative of kidney allograft injury. J Extracell Vesicles. 2022; 11(9):e12268. PMC: 9503341. DOI: 10.1002/jev2.12268. View

18.

Qu X, Li Q, Yang J, Zhao H, Wang F, Zhang F . Double-Stranded DNA in Exosomes of Malignant Pleural Effusions as a Novel DNA Source for EGFR Mutation Detection in Lung Adenocarcinoma. Front Oncol. 2019; 9:931. PMC: 6773809. DOI: 10.3389/fonc.2019.00931. View

19.

McKiernan J, Donovan M, ONeill V, Bentink S, Noerholm M, Belzer S . A Novel Urine Exosome Gene Expression Assay to Predict High-grade Prostate Cancer at Initial Biopsy. JAMA Oncol. 2016; 2(7):882-9. DOI: 10.1001/jamaoncol.2016.0097. View

20.

Zhu Q, Cheng L, Deng C, Huang L, Li J, Wang Y . The genetic source tracking of human urinary exosomes. Proc Natl Acad Sci U S A. 2021; 118(43). PMC: 8639375. DOI: 10.1073/pnas.2108876118. View