Xu Yong, Zhang Peng, Tan Yizhou, Jia Zhuo, Chen Guangfu, Niu Yinong, Xiao Jing, Sun Shengkun, Zhang Xu
Department of Urology, Chinese PLA General Hospital, Beijing, China.
Department of Laser Medicine, Chinese PLA General Hospital, Beijing, China.
Transl Androl Urol. 2021 Feb;10(2):809-820. doi: 10.21037/tau-20-1057.
Extracellular vesicles (EVs) have showed promising potential in liquid biopsy of cancer. In present study, we evaluate the feasibility to diagnose bladder cancer using EVs RNA markers identified from public tissue RNA sequencing data.
We used urine samples from a cohort of population with suspected bladder cancer. Disease status (i.e., primary or recurrent bladder cancer) was diagnosed by cystoscopy. A prediction model including the expression of multiple RNAs in urinary EVs were developed in training cohort (n=368, 126 bladder cancer and 242 negative controls). The performance of optimal model (ExoPanel) consists of five mRNAs (MYBL2, TK1, UBE2C, KRT7, S100A2) was further assessed by a validation cohort (n=155, 56 bladder cancer and 99 negative controls).
The performance of ExoPanel in training cohort was AUC 0.7759 (95% CI: 0.7259-0.8260), NPV 90.34% (95% CI: 84.04-94.42%), SN 88.89% (95% CI: 81.75-93.57%), and SP 54.13% (95% CI: 47.63-60.50%) respectively. In the validation cohort, the performance of this model was AUC 0.8402 (95% CI: 0.7690-0.9114), NPV 90.91% (95% CI: 79.29-96.60%), SN 91.07% (95% CI: 79.63-96.67%), and SP 50.51% (95% CI: 40.34-60.63%). Using this model, it is possible to rule out a significant number of non cancer patients, thus reduce the unnecessary operation of cystoscopy.
We discovered a panel of five mRNAs, and evaluated its potential to facilitate bladder cancer diagnosis by analyzing their expression in urinary EVs.
细胞外囊泡(EVs)在癌症液体活检中显示出了良好的潜力。在本研究中,我们评估了使用从公共组织RNA测序数据中鉴定出的EVs RNA标志物诊断膀胱癌的可行性。
我们使用了一组疑似膀胱癌人群的尿液样本。通过膀胱镜检查诊断疾病状态(即原发性或复发性膀胱癌)。在训练队列(n = 368,126例膀胱癌患者和242例阴性对照)中开发了一个包括尿EVs中多种RNA表达的预测模型。由五个mRNA(MYBL2、TK1、UBE2C、KRT7、S100A2)组成的最佳模型(外显子组)的性能在验证队列(n = 155,56例膀胱癌患者和99例阴性对照)中进一步评估。
外显子组在训练队列中的性能分别为AUC 0.7759(95%CI:0.7259 - 0.8260)、NPV 90.34%(95%CI:84.04 - 94.42%)、SN 88.89%(95%CI:81.75 - 93.57%)和SP 54.13%(95%CI:47.63 - 60.50%)。在验证队列中,该模型的性能为AUC 0.8402(95%CI:0.7690 - 0.9114)、NPV 90.91%(95%CI:79.29 - 96.60%)、SN 91.07%(95%CI:从79.63 - 96.67%)和SP 50.51%(95%CI:40.34 - 60.63%)。使用该模型,可以排除大量非癌症患者,从而减少不必要的膀胱镜检查手术。
我们发现了一组五个mRNA,并通过分析它们在尿EVs中的表达评估了其促进膀胱癌诊断的潜力。