Abstract Early prevention of renal cell carcinoma needs a reliable and robust bioassay to evaluate kidney cancer patients. As a novel class of regulatory molecules in cellular activity, the recent studies showed that microRNAs had tissue-specific patterns and were able to distinguish the cancer from benign disease. We explored the diagnostic value of urine microRNAs from a cohort of 160 individuals: 80 patients with renal clear cell carcinoma and 80 normal control individuals. Material and methods: The renal clear cell carcinomas cohort included 63% stage I cases, 10% stage II cases, 19% stage III cases, 7% stage IV cases, 1% unknown cases. Normal control cohort included 34% diverticulosis cases, 15% bariatric surgery cases, 14% diverticulitis cases, 15% hernia surgery cases, 10% hemorrhoids cases and 12% other non-cancer conditions. Every 10 urine samples were pooled together and subjected to microRNA extraction. The Norgen Biotek urine microRNA purification kit was used for total microRNA extraction (including free floating microRNAs and microRNAs from exfoliated cells) in the pooled urine samples. Urine microRNA expression profiling was performed using nCounter miRNA Expression Assay. After ligation and purification, hybridized microRNAs sequences were label by specific color codes and quantified using nCounter Digital Analyzer, then the data were normalized to the sum of the microRNAs within each pooled sample before statistic analysis. Result: comparing to normal control urine samples, microRNA-21-5p expression showed upregulation in kidney urine samples, which is consistent with TCGA kidney cancer tissue profiling results. Some recent studies also demonstrated that microRNA-21 may act as an oncomir in prostate, lung and colorectal cancers. We also observed that microRNA-1268a and microRNA-549 were highly expressed in urine samples from renal cell carcinoma patients. Conclusion: These findings indicate that in urine microRNA-21-5p may serve as a potential molecular marker for renal cell carcinoma and provide a new approach in the diagnosis of kidney cancer. Note: This abstract was not presented at the meeting. Citation Format: Wei Meng, Hansjuerg Alder, Kirsteen Maclean, Simon Kirste, Petra Stegmaier, Anca Grosu, Arnab Chakravarti, Tim Lautenschlaeger. MicroRNA-21-5p upregulation in urine samples serves as novel biomarkers for early stage renal cell carcinoma patients diagnosis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 889. doi:10.1158/1538-7445.AM2014-889