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BACKGROUND: MicroRNA (miRNA) is involved in the regulation of mRNA and has a role in tumorigenesis, but data about their specific role in clear cell renal cell carcinoma (ccRCC) is evolving. We aimed to identify miRNAs involved in the progression of ccRCC to metastasis.
METHODS: Total RNA was isolated from FFPE normal kidney and primary tumor from patients diagnosed with ccRCC. Samples were grouped as normal kidney, localized (T1 or T2) tumor, primary tumor with metastatic disease, or primary tumor from patients who progressed to metastatic ccRCC following surgery. MiRNAs were profiled by microarray on pooled samples within each group. Validation of miRNAs was performed on individual samples using qRT-PCR.
RESULTS: There were 257 differentially expressed miRNAs, 137 up-regulated and 120 down-regulated, between cancerous samples and normal tissue. Hierarchical cluster analysis revealed two main branches; one containing the normal pool and the other consisting of the three cancer pools. Within the cancer branch, the local pool was basal while the metastatic pool was apical with the progressor pool in between. Forty-six miRNAs were differentially expressed in either the progressor or metastatic group compared to the localized group. Further analysis showed that samples from the group of patients progressing to metastatic disease expressed miRNAs that correlated with samples within each the local group and metastatic group.
CONCLUSIONS: This study identified miRNAs separating normal from ccRCC samples. Additionally, we identified miRNAs that correlated with ccRCC progression to metastatic disease, many of which correlate with previously published metastasis-associated miRNAs. Our goal is the development of a miRNA profile predictive of metastatic ccRCC progression.