MicroRNA molecular profiling from matched tumor and bio-fluids in bladder cancer.
MicroRNA molecular profiling from matched tumor and bio-fluids in bladder cancer.
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DOI：
10.1186/s12943-015-0466-2
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发表时间：
2015-11-14
期刊：
影响因子：
37.3
通讯作者：
Marsit CJ
中科院分区：
文献类型：
--
作者：
Armstrong DA;Green BB;Seigne JD;Schned AR;Marsit CJ
MicroRNA由于其在包括尿液和血浆在内的许多体液中的存在和稳定性而被鉴定为潜在的癌症生物标志物，但是这些信使在各种生物介质中的表达模式的关系尚未得到解决，并且可以提供重要的信息，以便将这些生物标志物转化为流行病学或临床用途。我们分析了来自膀胱癌患者的匹配的FFPE-肿瘤组织、血浆、尿外泌体（n = 16）和WBC（n = 11）的microRNA，使用Nanostring miRNA测定和液滴数字PCR进行验证。使用Pearson相关性来比较培养基之间的表达。从特定的生物样本来源中检测到许多microRNA并重叠。miR-4454和miR-21的过度表达存在于三个来源：肿瘤、白细胞和尿液。此外，miR-15 b-5 p、miR-126- 3 p、miR-93- 5 p和miR-150- 5 p在肿瘤/WBC中常见，而miR-720/3007 a、miR-205、miR-200 c-3 p和miR-29 b-3 p在肿瘤/尿液中常见。在肿瘤与WBC（r = 0.418 p < 0.001）和肿瘤与尿液（r = 0.38 p < 0.001）中的对数调整平均miRNA计数之间注意到显著关联。没有观察到肿瘤与血浆外泌体miR的关联（r = 0.07 p = 0.06）。来自患者中匹配样品的microRNA谱显示，在膀胱肿瘤中上调的显著数量的microRNA在同一患者的尿外泌体和WBC中是可识别的，但在血浆中不是。这项研究证明了在同一患者的生物介质中检测到的miRNA之间的不同关系，并用于告知尿基microRNA作为膀胱癌和潜在其他恶性肿瘤的生物标志物的潜力。本文的在线版本（doi：10.1186/s12943-015-0466-2）包含补充材料，可供授权用户使用。
MicroRNAs have been identified as potential cancer biomarkers due to their presence and stability in many body fluids including urine and plasma, but the relationship of the pattern of expression of these messengers across various biological media has not been addressed and could provide important information in order to translate these biomarkers for epidemiologic or clinical use. We analyzed microRNA of matched FFPE-tumor tissue, plasma, urine exosomes (n = 16) and WBCs (n = 11) from patients with bladder cancer, using Nanostring miRNA assays and droplet digital PCR for validation. Pearson correlations were used to compare expression between media. Numerous microRNAs were detected and overlapping from specific bio-specimen sources. MiR-4454 and miR-21 overexpression was found in three sources: tumor, WBCs and urine. Additionally, miR-15b-5p, miR-126-3p, miR-93-5p, and miR-150-5p were common to tumor/WBCs, while miR-720/3007a, miR-205, miR-200c-3p and miR-29b-3p common to tumor/urine. Significant associations were noted between the log-adjusted average miRNA counts in tumor vs. WBCs (r = 0.418 p < 0.001), and tumor vs. urine (r = 0.38 p < 0.001). No association was seen tumor vs. plasma exosome miRs (r = 0.07 p = 0.06). MicroRNA profiling from matched samples in patients shows a significant number of microRNAs up regulated in bladder tumors are identifiable in urine exosomes and WBCs of the same patient, but not in blood plasma. This study demonstrated varying relationships between miRNA detected in biological media from the same patient, and serves to inform the potential of urine-based microRNAs as biomarkers for bladder cancer and potentially other malignancies. The online version of this article (doi:10.1186/s12943-015-0466-2) contains supplementary material, which is available to authorized users.