Plasma extracellular vesicle circRNA signature and resistance to abiraterone in metastatic castration-resistant prostate cancer
Plasma extracellular vesicle circRNA signature and resistance to abiraterone in metastatic castration-resistant prostate cancer
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DOI：
10.1038/s41416-023-02147-8
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发表时间：
2023-01
影响因子：
8.8
通讯作者：
W. Tao;Zi-Huan Luo;Yadi He;Bang-Yu Wang;Tao-lin Xia;Wei-ming Deng;Ling-Xiao Zhang;Xiu-Mei Tang;Zhanao Meng;Xin Gao;Liao-Yuan Li
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作者：
W. Tao;Zi-Huan Luo;Yadi He;Bang-Yu Wang;Tao-lin Xia;Wei-ming Deng;Ling-Xiao Zhang;Xiu-Mei Tang;Zhanao Meng;Xin Gao;Liao-Yuan Li
背景我们的目的是开发和验证一种基于血浆细胞外囊泡环状RNA(CircRNA)的信号，可以预测转移性去势耐受前列腺癌(MCRPC)患者的总生存期(OS)。方法总共对来自四个机构的582名接受一线阿比特龙治疗的mCRPC患者进行了三个阶段的分类。在发现阶段，从30例具有或不具有早期进展的病例匹配的患者中获得30份血浆样本，以使用RNA测序来生成CircRNA表达谱。在训练阶段，在训练队列(n= 203)中使用数字液滴聚合酶链式反应检测差异表达的CircRNA。使用最小绝对收缩和选择算子COX回归来构建CircRNA签名以预测OS。在验证阶段，这一标记的预后能力在两个外部队列(队列I，n= 183；队列II，n= 166)中进行了前瞻性验证。结果我们开发了一个基于CircCEP112、CircFAM13A、CircBRWD1、CircVPS13和CircMACROD2的五环RNA签名，成功地将患者分为高危和低危两组。这一标记的预后能力在两个外部队列中得到了前瞻性验证(P<； 0.0001，P<； 0.0001)。高风险评分的患者比低风险评分的患者的OS短。结论这种五圈RNA信号是接受阿比特龙治疗的mCRPC患者OS的可靠预测指标。
BackgroundWe aimed to develop and validate a plasma extracellular vesicle circular RNA (circRNA)-based signature that can predict overall survival (OS) in first-line abiraterone therapy for metastatic castration-resistant prostate cancer (mCRPC) patients.MethodsIn total, 582 mCRPC patients undergoing first-line abiraterone therapy from four institutions were sorted by three phases. In the discovery phase, 30 plasma samples from 30 case-matched patients with or without early progression were obtained to generate circRNA expression profiles using RNA sequencing. In the training phase, differentially expressed circRNAs were examined using digital droplet PCR in a training cohort (n= 203). The circRNA signature was constructed using a least absolute shrinkage and selection operator Cox regression to predict OS. In the validation phase, the prognostic ability of this signature was prospectively validated in two external cohorts (Cohort I,n= 183; Cohort II,n= 166).ResultsWe developed a five-circRNA signature, based oncircCEP112, circFAM13A, circBRWD1, circVPS13CandcircMACROD2, which successfully stratified patients into high-risk and low-risk groups. The prognostic ability of this signature was prospectively validated in two external cohorts (P< 0.0001,P< 0.0001). Patients with high-risk scores had shorter OS than patients with low-risk scores.ConclusionThis five-circRNA signature is a reliable predictor of OS for mCRPC patients undergoing abiraterone.