The James Buchanan Brady Urological Institute, Department of Urology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
The James Buchanan Brady Urological Institute, Department of Urology, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Urology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
Urology. 2022 Feb;160:87-93. doi: 10.1016/j.urology.2021.11.002. Epub 2021 Nov 15.
To propose EV-derived mRNA as a potential diagnostic biomarker detecting the presence of clear cell renal cell carcinoma (ccRCC). There is currently no kidney cancer specific screening or diagnostic technology. Therefore, one-third of kidney cancer diagnoses occur after the cancer has metastasized and is past curative measures MATERIALS AND METHODS: Urine, plasma, normal tumor adjacent tissue, and tumor tissue was collected from a limited population of ccRCC patients. Extracellular vesicle (EV) isolation was performed on each sample, followed by mRNA extraction from isolated EVs. NanoString nCounter technology was utilized to count the mRNA transcripts present in matched plasma, urine, tumor tissue, and normal tumor adjacent tissue samples.
770 mRNA transcripts related to gene's affecting cancer's progression and metastasis processes were evaluated. Four EV derived mRNA transcripts (ALOX5, RBL2, VEGFA, TLK2) were found specific to urine and tumor tissue samples.
Four candidate RCC-specific urine EV biomarkers were identified. However, due to the lack of a true negative control and urine collection techniques, further re-examination is necessary for validation. This study demonstrates the promise of defining disease-specific EV biomarkers in liquid biopsy patient samples.
提出 EV 衍生的 mRNA 作为检测透明细胞肾细胞癌 (ccRCC) 存在的潜在诊断生物标志物。目前尚无专门针对肾癌的筛查或诊断技术。因此,三分之一的肾癌诊断发生在癌症转移且已超过治疗措施的阶段。
从有限数量的 ccRCC 患者中收集尿液、血浆、正常肿瘤旁组织和肿瘤组织。对每个样本进行细胞外囊泡 (EV) 分离,然后从分离的 EV 中提取 mRNA。利用 NanoString nCounter 技术对匹配的血浆、尿液、肿瘤组织和正常肿瘤旁组织样本中的 mRNA 转录本进行计数。
评估了 770 个与影响癌症进展和转移过程的基因相关的 mRNA 转录本。发现 4 种 EV 衍生的 mRNA 转录本(ALOX5、RBL2、VEGFA、TLK2)在尿液和肿瘤组织样本中具有特异性。
鉴定了 4 种候选的 RCC 特异性尿液 EV 生物标志物。然而,由于缺乏真正的阴性对照和尿液采集技术,需要进一步重新检查以验证。本研究证明了在液体活检患者样本中定义疾病特异性 EV 生物标志物的潜力。