Exosomal TUBB3 mRNA expression of metastatic castration-resistant prostate cancer patients: Association with patient outcome under abiraterone.
Exosomal TUBB3 mRNA expression of metastatic castration-resistant prostate cancer patients: Association with patient outcome under abiraterone.
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转移性去势抵抗性前列腺癌患者的外泌体 TUBB3 mRNA 表达：与阿比特龙治疗下患者预后的相关性。
DOI：
10.1002/cam4.4168
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发表时间：
2021-09
期刊：
影响因子：
4
通讯作者：
Zeng H
中科院分区：
文献类型：
--
作者：
Zhu S;Ni Y;Sun G;Wang Z;Chen J;Zhang X;Zhao J;Zhu X;Dai J;Liu Z;Liang J;Zhang H;Zhang Y;Shen P;Zeng H
利用ddPCR定量转移性去势抵抗性前列腺癌（mCRPC）患者血浆外泌体III类β -微管蛋白（βIII -微管蛋白，TUBB3，由TUBB3基因编码）mRNA表达，并研究其表达与阿比特龙疗效的关系。前瞻性地采集52例使用阿比特龙作为一线治疗的mCRPC患者的血液样本，在阿比特龙开始治疗前测量血浆外泌体TUBB3 mRNA的表达值。研究终点是PSA缓解率、PSA无进展生存期（PSA - PFS）和总生存期（OS，从CRPC到死亡）。外泌体TUBB3阳性表达的患者PSA - PFS较短（TUBB3阴性vs. TUBB3阳性：11.0 vs. 7.9个月；p = 0.014）。进一步分析表明，外泌体TUBB3强阳性（bbb20拷贝/20µl）患者的PSA - PFS更短（阴性TUBB3 vs阳性TUBB3[<20拷贝/20µl] vs强阳性TUBB3[>20拷贝/20µl]: 11.0 vs. 8.3 vs. 3.6个月，p = 0.005）。在多变量分析中，TUBB3 (+) （HR: 2.114, p = 0.033）和ECOG评分bbbb2 （HR: 3.039, p = 0.006）是PSA - PFS不良的独立预后指标。PSA反应与OS无显著性差异。外泌体TUBB3 mRNA表达水平与mCRPC患者阿比特龙PSA - PFS差相关。外泌体TUBB3的检测对其治疗有价值。在这项研究中，我们利用ddPCR方法定量测量外泌体TUBB3 mRNA的表达，提出了一种新的、无创的mCRPC患者阿比特龙耐药生物标志物。我们发现，在mCRPC患者接受一线阿比特龙治疗后，较高的TUBB3水平与较短的进展时间相关。
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. 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). 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. 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. In this study, we presented this novel, non‐invasive biomarker for abiraterone resistance in mCRPC patients using a ddPCR approach to quantificationally measure the exosomal TUBB3 mRNA expression. We found that a higher TUBB3 level is correlated with shorter progression time after first‐line abiraterone treatment in mCRPC patients.
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