MicroRNA molecular profiling from matched tumor and bio-fluids in bladder cancer

Molecular Cancer

Research

Alan R. Schned¹  John D. Seigne²  Benjamin B. Green³  David A. Armstrong³  Carmen J. Marsit⁴ 

[1] Department of Pathology, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA;Department of Surgery (Urology), Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA;Departments of Pharmacology and Toxicology, Geisel School of Medicine at Dartmouth, Hanover, NH, USA;Departments of Pharmacology and Toxicology, Geisel School of Medicine at Dartmouth, Hanover, NH, USA;Department of Epidemiology, Geisel School of Medicine at Dartmouth, Hanover, NH, USA;

关键词: Bladder Cancer;    MicroRNA;    Urine;    Plasma;    Exosomes;    NanoString;    Droplet digital PCR;   

DOI  :  10.1186/s12943-015-0466-2

 received in 2015-08-21, accepted in 2015-11-05,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundMicroRNAs 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.MethodsWe 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.ResultsNumerous 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).ConclusionsMicroRNA 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.

【 授权许可】

CC BY   
© Armstrong et al. 2015