Abstract
BackgroundMicroRNA expression is altered in cancer cells, and microRNAs could serve as diagnostic/prognostic biomarker for cancer patients. Our study was designed to analyze circulating serum microRNAs in patients with renal cell carcinoma (RCC).Methodology/Principal FindingsWe first explored microRNA expression profiles in tissue and serum using TaqMan Low Density Arrays in each six malignant and benign samples: Although 109 microRNAs were circulating at higher levels in cancer patients' serum, we identified only 36 microRNAs with up-regulation in RCC tissue and serum of RCC patients. Seven candidate microRNAs were selected for verification based on the finding of up-regulation in serum and tissue of RCC patients: miR-7-1*, miR-93, miR-106b*, miR-210, miR-320b, miR-1233 and miR-1290 levels in serum of healthy controls (n = 30) and RCC (n = 33) patients were determined using quantitative real-time PCR (TaqMan MicroRNA Assays). miR-1233 was increased in RCC patients, and thus validated in a multicentre cohort of 84 RCC patients and 93 healthy controls using quantitative real-time PCR (sensitivity 77.4%, specificity 37.6%, AUC 0.588). We also studied 13 samples of patients with angiomyolipoma or oncocytoma, whose serum miR-1233 levels were similar to RCC patients. Circulating microRNAs were not correlated with clinical-pathological parameters.Conclusions/SignificanceMicroRNA levels are distinctly increased in cancer patients, although only a small subset of circulating microRNAs has a tumor-specific origin. We identify circulating miR-1233 as a potential biomarker for RCC patients. Larger-scaled studies are warranted to fully explore the role of circulating microRNAs in RCC.
Highlights
Kidney cancer is one of the most common malignancies in developed countries [1]
The most common renal tumor is clear cell renal cell carcinoma, but other histological subtypes of renal cell carcinoma or non-malignant renal tumors are more or less difficult to differentiate by imaging modalities, and additional diagnostic tools are warranted to optimize the management of patients with renal tumors
We determined the microRNA profile in serum from these patients, and compared the expression profile to healthy individuals; in order to control the isolation efficiency, the microRNA expression was normalized to miR-39, which was spiked to serum prior the RNA isolation procedure
Summary
Kidney cancer is one of the most common malignancies in developed countries [1]. Renal tumors are asymptomatic and nonpalpable in early stages; more than 50% of renal tumors are detected incidentally by imaging to investigate non-specific symptoms. The most common renal tumor is clear cell renal cell carcinoma (ccRCC), but other histological subtypes of renal cell carcinoma (i.e. papillary, pRCC; or chromophobe RCC, chRCC) or non-malignant renal tumors (i.e. oncocytoma and angiomyolipoma) are more or less difficult to differentiate by imaging modalities, and additional diagnostic tools are warranted to optimize the management of patients with renal tumors. MicroRNA expression profiles allow distinguishing malignant and non-malignant tissue, and distinguishing different tumor entities.[3] MicroRNAs are circulating in a cell-free form in blood [4,5,6], most probably in exosomes which protect them against degradation by RNase [4,5]. MicroRNA expression is altered in cancer cells, and microRNAs could serve as diagnostic/prognostic biomarker for cancer patients. Our study was designed to analyze circulating serum microRNAs in patients with renal cell carcinoma (RCC)
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