Renal cell carcinoma (RCC) is among the top 10 most common malignancies and represents on average over 90% of all malignancies of the kidney that occur in adults. In 2012approximately 64,000 individuals were diagnosed, with an estimated 13,570 dying from this disease in the United States. The incidence of RCC has been increasing and its mortality rate has reached 40%. The 5-year survival of RCC is estimated to be approximately 55% and that of metastatic RCC is approximately 10%. Surgical excision of the tumor at a localized stage remains the mainstay for curative therapy. However, nearly 40% of RCC patients lack clinical symptoms, and are usually only diagnosed in the advanced stage when the tumor has already extensively progressed and distantly metastasized due to the lack of early-stage diagnostic markers. Therefore, new strategies for early detection are essential in improving RCC patient outcomes.
MicroRNAs (miRNAs), small noncoding RNAs that posttranscriptionally regulate genes by binding to the untranslated region (3'UTR) of target mRNAs, are involved in various physiological and pathological processes, particularly in development of cancer. Specific expression profiles of miRNAs have been shown in a variety of cancers, including RCC. More importantly, miRNAs are thought to be excellent biomarkers for cancer diagnosis and prognosis. Recent studies by our group and others have demonstrated that miRNAs are stably detectable in the circulation and can serve as potential non-invasive biomarkers for cancer (1-4).
By employing reverse transcription (RT)-PCR-based TaqMan Low Density Array scanning together with confirmation using a quantitative reverse-transcription PCR (RT-qPCR) assay based on a reliable internal reference gene, we found a panel of miRNAs was markedly altered in sera of patients with RCC as compared with that of age/sex-matched noncancer controls. More importantly, our results showed that this panel of miRNAs had high sensitivity and specificity (>70%) for distinguishing early stage RCC from controls. In addition, we found that some of these miRNAs played an important role in the development and progression of RCC by regulating their target genes.
Can circulating miRNAs can be a novel screening tool for RCC? Do miRNAs have a potential use as a therapeutic target for RCC?
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