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Introduction:
MicroRNAs (miRNAs) are promising cancer biomarkers; however, miRNA profiling of upper tract urothelial carcinoma (UTUC) tumors is largely unexplored. Concerns remain over accurate grading and staging of UTUC secondary to inadequate tissue sampling. Furthermore, accurate knowledge of the biology of these tumors would allow tailored treatment for patients who are not candidates for a nephroureterectomy (NU). We aimed to identify a miRNA expression profile which can differentiate low- and high-grade UTUC.
Materials & Methods:
Total RNA was extracted from Formalin-fixed, paraffin-embedded samples from 2005 to 2013 under an IRB-approved study. NU samples were divided into low- and high-grade pools (n=50) based on pathology. Sample pools from each group were profiled via miRNA RT-qPCR array and validation was performed on individual NU and biopsy samples.
Results:
Array analysis of 752 miRNA identified 114 miRNA with > 2 fold differential expression between the low- and high-grade pools. Of these, 63 were up-regulated and 51 were down-regulated in the high-grade pool. Several miRNA were further validated by qRT-PCR on individual samples confirming differential expression. A number of these miRNAs have previously been implicated in aggressive bladder urothelial carcinoma.
Conclusions:
We have identified miRNA which discriminate low- and high-grade disease in NU specimens. Several of these miRNA were differentially expressed in biopsy specimens which may enhance the diagnosis of UTUC. Furthermore, we are prospectively analyzing these miRNAs in urine to develop a non-invasive assay to detect UTUC. The miRNA expression profile may also aid in personalizing treatment and follow-up based on tumor biology.