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

Abstract

BACKGROUND:

To use ddPCR to quantify plasma exosomal class III β-tubulin (βIII-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 µl) was associated with even shorter PSA-PFS (negative TUBB3 vs. positive TUBB3 [<20 copies/20 µl] vs. strongly positive TUBB3 [>20 copies/20 µl]: 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.

• Authors: Sha Zhu, Yuchao Ni, Guangxi Sun, Zilin Wang, Junru Chen, Xingming Zhang, Jinge Zhao, Xudong Zhu, Jindong Dai, Zhenhua Liu, Jiayu Liang, Haoran Zhang, Yaowen Zhang, Pengfei Shen, Hao Zeng
• Journal: Cancer medicine (Cancer Med) Vol. 10 Issue 18 Pg. 6282-6290 (09 2021) ISSN: 2045-7634 [Electronic] United States
• PMID: 34318630 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Chemical References

• Androstenes
• Biomarkers, Tumor
• RNA, Messenger
• TUBB3 protein, human
• Tubulin
• KLK3 protein, human
• Kallikreins
• Prostate-Specific Antigen
• abiraterone

Topics

• Aged
• Androstenes (pharmacology, therapeutic use)
• Biomarkers, Tumor (blood, genetics)
• Drug Resistance, Neoplasm (genetics)
• Exosomes (metabolism)
• Gene Expression Regulation, Neoplastic
• Humans
• Kallikreins (blood)
• Male
• Progression-Free Survival
• Prospective Studies
• Prostate-Specific Antigen (blood)
• Prostatic Neoplasms, Castration-Resistant (blood, drug therapy, mortality, secondary)
• RNA, Messenger (blood)
• Risk Assessment (methods, statistics & numerical data)
• Tubulin (blood, genetics)