4.6 Article

Exosomal TUBB3 mRNA expression of metastatic castration-resistant prostate cancer patients: Association with patient outcome under abiraterone

Journal

CANCER MEDICINE
Volume 10, Issue 18, Pages 6282-6290

Publisher

WILEY
DOI: 10.1002/cam4.4168

Keywords

abiraterone acetate; exosomes; messenger; prostatic neoplasms; RNA; TUBB3

Categories

Funding

  1. Natural Science Foundation of China [NSFC 81974398, 81902577]
  2. China Postdoctoral Science Foundation [2020M673239]
  3. 1.3.5 project for disciplines of excellence, West China Hospital, Sichuan University [0040205301E21]

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The expression level of exosomal TUBB3 mRNA is associated with poor PSA-PFS in mCRPC patients treated with abiraterone, with TUBB3 (+) and ECOG score >2 being independent predictors of unfavorable PSA-PFS.
Background To use ddPCR to quantify plasma exosomal class III beta-tubulin (beta III-tubulin, TUBB3, encoded by the TUBB3 gene) mRNA expression in metastatic castration-resistant prostate cancer (mCRPC) patients, and study the association of this expression with abiraterone efficacy. Methods Blood samples were prospectively collected from 52 mCRPC patients using abiraterone as first-line therapy to measure plasma exosomal TUBB3 mRNA expression value before the initiation of abiraterone. Study endpoints were PSA response rate, PSA-progression-free survival (PSA-PFS), and overall survival (OS, from CRPC to death). Results Patients with positive exosomal TUBB3 expression showed shorter PSA-PFS (negative TUBB3 vs. positive TUBB3: 11.0 vs. 7.9 months; p = 0.014). Further analysis demonstrated that patients with strongly positive exosomal TUBB3 (>20 copies/20 mu l) was associated with even shorter PSA-PFS (negative TUBB3 vs. positive TUBB3 [TUBB3 [>20 copies/20 mu l]: 11.0 vs. 8.3 vs. 3.6 months, p = 0.005). In multivariate analyzes, TUBB3 (+) (HR: 2.114, p = 0.033) and ECOG score >2 (HR: 3.039, p = 0.006) were independent prognosticators of poor PSA-PFS. PSA response and OS did not present significant differences. Conclusion The exosomal TUBB3 mRNA expression level is associated with poor PSA-PFS of abiraterone in mCRPC patients. The detection of exosomal TUBB3 can be valuable in their management.

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