Comparison of androgen receptor mutation detection between plasma extracellular vesicle DNA and cell-free DNA and its relationship to prostate cancer prognosis

Background In liquid biopsy, mutation detection is primarily performed using cell-free DNA (cfDNA). However, the numerous advantages of extracellular vesicle (EV) DNA for mutation detection have gradually garnered the attention of researchers in recent years. This study aimed to compare the differen...

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Main Authors: Ting Ding, Xiao Li, Longlong Zhang, Zhen Wei, Chaoliang Xiong, Hong Wang, Xiaoke Hao, Xianfei Zeng
Format: Article
Language:English
Published: Taylor & Francis Group 2024-12-01
Series:Annals of Medicine
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Online Access:https://www.tandfonline.com/doi/10.1080/07853890.2024.2426770
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author Ting Ding
Xiao Li
Longlong Zhang
Zhen Wei
Chaoliang Xiong
Hong Wang
Xiaoke Hao
Xianfei Zeng
author_facet Ting Ding
Xiao Li
Longlong Zhang
Zhen Wei
Chaoliang Xiong
Hong Wang
Xiaoke Hao
Xianfei Zeng
author_sort Ting Ding
collection DOAJ
description Background In liquid biopsy, mutation detection is primarily performed using cell-free DNA (cfDNA). However, the numerous advantages of extracellular vesicle (EV) DNA for mutation detection have gradually garnered the attention of researchers in recent years. This study aimed to compare the differences between EV DNA and cfDNA in mutation detection and explore the role of plasma androgen receptor (AR) mutations in the prognosis of prostate cancer (PCa).Methods We compared the biological characteristics of plasma extracellular vesicle DNA (p-EV DNA) and cfDNA by capillary electrophoresis and concentration detection. Subsequently, we performed pan-oncogene-targeted sequencing in paired tissue and plasma samples from five patients with PCa to verify the feasibility of mutation detection using p-EV DNA and cfDNA. Further, we conducted AR mutation detection in expanded samples to compare the differences between EV DNA and cfDNA in mutation detection and to analyse their role in PCa.Results p-EV DNA fragments were larger than plasma cell-free DNA (p-cfDNA) fragments; however, there was no significant difference in their concentrations in the plasma of patients with PCa. Feasibility analysis revealed that major mutations associated with PCa detected in tissue samples could be identified in both p-EV DNA and p-cfDNA. Advantage comparison found that, although cfDNA could detect more mutations, AR mutations in EV DNA were more strongly associated with a poor prognosis of PCa than cfDNA.Conclusion Mutation detection using either EV DNA or cfDNA is both feasible in PCa liquid biopsies, and EV DNA AR mutations have an advantage in prognostic assessment for PCa. This study lays the foundation for future research on EV DNA-related biomarkers.
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spelling doaj-art-e2c16df8d4914ea69cbbddf88d09ba392024-11-13T13:15:01ZengTaylor & Francis GroupAnnals of Medicine0785-38901365-20602024-12-0156110.1080/07853890.2024.2426770Comparison of androgen receptor mutation detection between plasma extracellular vesicle DNA and cell-free DNA and its relationship to prostate cancer prognosisTing Ding0Xiao Li1Longlong Zhang2Zhen Wei3Chaoliang Xiong4Hong Wang5Xiaoke Hao6Xianfei Zeng7School of Medicine, Northwest University, Xi’an, ChinaSchool of Medicine, Northwest University, Xi’an, ChinaDepartment of Urology, Xijing Hospital, Fourth Military Medical University (Air Force Medical University), Xi’an, ChinaSchool of Medicine, Northwest University, Xi’an, ChinaDepartment of Clinical Laboratory, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaDepartment of Urology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaSchool of Medicine, Northwest University, Xi’an, ChinaSchool of Medicine, Northwest University, Xi’an, ChinaBackground In liquid biopsy, mutation detection is primarily performed using cell-free DNA (cfDNA). However, the numerous advantages of extracellular vesicle (EV) DNA for mutation detection have gradually garnered the attention of researchers in recent years. This study aimed to compare the differences between EV DNA and cfDNA in mutation detection and explore the role of plasma androgen receptor (AR) mutations in the prognosis of prostate cancer (PCa).Methods We compared the biological characteristics of plasma extracellular vesicle DNA (p-EV DNA) and cfDNA by capillary electrophoresis and concentration detection. Subsequently, we performed pan-oncogene-targeted sequencing in paired tissue and plasma samples from five patients with PCa to verify the feasibility of mutation detection using p-EV DNA and cfDNA. Further, we conducted AR mutation detection in expanded samples to compare the differences between EV DNA and cfDNA in mutation detection and to analyse their role in PCa.Results p-EV DNA fragments were larger than plasma cell-free DNA (p-cfDNA) fragments; however, there was no significant difference in their concentrations in the plasma of patients with PCa. Feasibility analysis revealed that major mutations associated with PCa detected in tissue samples could be identified in both p-EV DNA and p-cfDNA. Advantage comparison found that, although cfDNA could detect more mutations, AR mutations in EV DNA were more strongly associated with a poor prognosis of PCa than cfDNA.Conclusion Mutation detection using either EV DNA or cfDNA is both feasible in PCa liquid biopsies, and EV DNA AR mutations have an advantage in prognostic assessment for PCa. This study lays the foundation for future research on EV DNA-related biomarkers.https://www.tandfonline.com/doi/10.1080/07853890.2024.2426770Liquid biopsyextracellular vesicle DNAcell-free DNAAR mutationsprostate cancer
spellingShingle Ting Ding
Xiao Li
Longlong Zhang
Zhen Wei
Chaoliang Xiong
Hong Wang
Xiaoke Hao
Xianfei Zeng
Comparison of androgen receptor mutation detection between plasma extracellular vesicle DNA and cell-free DNA and its relationship to prostate cancer prognosis
Annals of Medicine
Liquid biopsy
extracellular vesicle DNA
cell-free DNA
AR mutations
prostate cancer
title Comparison of androgen receptor mutation detection between plasma extracellular vesicle DNA and cell-free DNA and its relationship to prostate cancer prognosis
title_full Comparison of androgen receptor mutation detection between plasma extracellular vesicle DNA and cell-free DNA and its relationship to prostate cancer prognosis
title_fullStr Comparison of androgen receptor mutation detection between plasma extracellular vesicle DNA and cell-free DNA and its relationship to prostate cancer prognosis
title_full_unstemmed Comparison of androgen receptor mutation detection between plasma extracellular vesicle DNA and cell-free DNA and its relationship to prostate cancer prognosis
title_short Comparison of androgen receptor mutation detection between plasma extracellular vesicle DNA and cell-free DNA and its relationship to prostate cancer prognosis
title_sort comparison of androgen receptor mutation detection between plasma extracellular vesicle dna and cell free dna and its relationship to prostate cancer prognosis
topic Liquid biopsy
extracellular vesicle DNA
cell-free DNA
AR mutations
prostate cancer
url https://www.tandfonline.com/doi/10.1080/07853890.2024.2426770
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