School of Medicine, Northwest University, Xi'an, China.
Department of Clinical Laboratory, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Ann Med. 2024 Dec;56(1):2426770. doi: 10.1080/07853890.2024.2426770. Epub 2024 Nov 13.
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).
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.
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.
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.
在液体活检中，主要通过游离 DNA（cfDNA）进行突变检测。然而，近年来，细胞外囊泡（EV）DNA 用于突变检测的诸多优势逐渐引起了研究人员的关注。本研究旨在比较 EV DNA 和 cfDNA 在突变检测中的差异，并探讨血浆雄激素受体（AR）突变在前列腺癌（PCa）预后中的作用。
我们通过毛细管电泳和浓度检测比较了血浆细胞外囊泡 DNA（p-EV DNA）和 cfDNA 的生物学特征。随后，我们对 5 例 PCa 患者的组织和血浆配对样本进行了泛癌种靶向测序，以验证使用 p-EV DNA 和 cfDNA 进行突变检测的可行性。此外，我们在扩展样本中进行了 AR 突变检测，以比较 EV DNA 和 cfDNA 在突变检测中的差异，并分析它们在 PCa 中的作用。
p-EV DNA 片段大于血浆游离 DNA（p-cfDNA）片段；然而，在 PCa 患者的血浆中，它们的浓度没有显著差异。可行性分析显示，在组织样本中检测到的与 PCa 相关的主要突变也可在 p-EV DNA 和 p-cfDNA 中检测到。优势比较发现，尽管 cfDNA 可以检测到更多的突变，但 EV DNA 中的 AR 突变与 PCa 的不良预后的相关性强于 cfDNA。
在 PCa 的液体活检中，使用 EV DNA 或 cfDNA 进行突变检测都是可行的，并且 EV DNA AR 突变在 PCa 的预后评估中具有优势。本研究为未来 EV DNA 相关生物标志物的研究奠定了基础。
