Frontiers in Cell and Developmental Biology (Jan 2021)

The Identification of Plasma Exosomal miR-423-3p as a Potential Predictive Biomarker for Prostate Cancer Castration-Resistance Development by Plasma Exosomal miRNA Sequencing

  • Tianyu Guo,
  • Tianyu Guo,
  • Yang Wang,
  • Yang Wang,
  • Jing Jia,
  • Xueying Mao,
  • Elzbieta Stankiewicz,
  • Glenda Scandura,
  • Edwina Burke,
  • Lei Xu,
  • Lei Xu,
  • Jacek Marzec,
  • Jacek Marzec,
  • Caitlin R. Davies,
  • Jiaying Jasmin Lu,
  • Prabhakar Rajan,
  • Prabhakar Rajan,
  • Prabhakar Rajan,
  • Prabhakar Rajan,
  • Alistair Grey,
  • Alistair Grey,
  • Karen Tipples,
  • John Hines,
  • John Hines,
  • Sakunthala Kudahetti,
  • Tim Oliver,
  • Thomas Powles,
  • Constantine Alifrangis,
  • Constantine Alifrangis,
  • Manish Kohli,
  • Manish Kohli,
  • Greg Shaw,
  • Greg Shaw,
  • Greg Shaw,
  • Wen Wang,
  • Ninghan Feng,
  • Jonathan Shamash,
  • Daniel Berney,
  • Liang Wang,
  • Yong-Jie Lu,
  • Yong-Jie Lu

DOI
https://doi.org/10.3389/fcell.2020.602493
Journal volume & issue
Vol. 8

Abstract

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Castration-resistant prostate cancer (CRPC) is the major cause of death from prostate cancer. Biomarkers to improve early detection and prediction of CRPC especially using non-invasive liquid biopsies could improve outcomes. Therefore, we investigated the plasma exosomal miRNAs associated with CRPC and their potential for development into non-invasive early detection biomarkers for resistance to treatment. RNA-sequencing, which generated approximately five million reads per patient, was performed to identify differentially expressed plasma exosomal miRNAs in 24 treatment-naive prostate cancer and 24 CRPC patients. RT-qPCR was used to confirm the differential expressions of six exosomal miRNAs, miR-423-3p, miR-320a, miR-99a-5p, miR-320d, miR-320b, and miR-150-5p (p = 7.3 × 10−8, 0.0020, 0.018, 0.0028, 0.0013, and 0.0058, respectively) firstly in a validation cohort of 108 treatment-naive prostate cancer and 42 CRPC patients. The most significant differentially expressed miRNA, miR-423-3p, was shown to be associated with CRPC with area under the ROC curve (AUC) = 0.784. Combining miR-423-3p with prostate-specific antigen (PSA) enhanced the prediction of CRPC (AUC = 0.908). A separate research center validation with 30 treatment-naive and 30 CRPC patients also confirmed the differential expression of miR-423-3p (p = 0.016). Finally, plasma exosomal miR-423-3p expression in CRPC patients was compared to 36 non-CRPC patients under androgen depletion therapy, which showed significantly higher expression in CRPC than treated non-CRPC patients (p < 0.0001) with AUC = 0.879 to predict CRPC with no difference between treatment-naive and treated non-CRPC patients. Therefore, our findings demonstrate that a number of plasma exosomal miRNAs are associated with CRPC and miR-423-3p may serve as a biomarker for early detection/prediction of castration-resistance.

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