MicroRNAs in Renal Cell Carcinoma: Diagnostic Implications of Serum miR-1233 Levels

Background 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). Methodology/Principal Findings We 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/Significance MicroRNA 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.

[1]  E. Ng,et al.  Differential expression of microRNAs in plasma of patients with colorectal cancer: a potential marker for colorectal cancer screening , 2009, Gut.

[2]  George M Yousef,et al.  Accurate molecular classification of kidney cancer subtypes using microRNA signature. , 2011, European urology.

[3]  Hans Lehrach,et al.  MicroRNA profiling of clear cell renal cell cancer identifies a robust signature to define renal malignancy , 2009, Journal of cellular and molecular medicine.

[4]  Lianbo Yu,et al.  Detection of microRNA Expression in Human Peripheral Blood Microvesicles , 2008, PloS one.

[5]  C. Croce,et al.  A microRNA expression signature of human solid tumors defines cancer gene targets , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[6]  Jean-Jacques Patard,et al.  EAU guidelines on renal cell carcinoma: the 2010 update. , 2010, European urology.

[7]  A. Harris,et al.  Detection of elevated levels of tumour‐associated microRNAs in serum of patients with diffuse large B‐cell lymphoma , 2008, British journal of haematology.

[8]  Muneesh Tewari,et al.  Analysis of circulating microRNA biomarkers in plasma and serum using quantitative reverse transcription-PCR (qRT-PCR). , 2010, Methods.

[9]  Daniel B. Martin,et al.  Circulating microRNAs as stable blood-based markers for cancer detection , 2008, Proceedings of the National Academy of Sciences.

[10]  J. Ellinger,et al.  Hypermethylation of cell-free serum DNA indicates worse outcome in patients with bladder cancer. , 2008, The Journal of urology.

[11]  M. Seto,et al.  Genome‐wide microRNA expression profiling in renal cell carcinoma: significant down‐regulation of miR‐141 and miR‐200c , 2008, The Journal of pathology.

[12]  George M Yousef,et al.  Differential expression profiling of microRNAs and their potential involvement in renal cell carcinoma pathogenesis. , 2010, Clinical biochemistry.

[13]  Bin Tean Teh,et al.  MicroRNA profiling of human kidney cancer subtypes. , 2009, International journal of oncology.

[14]  T. Leung,et al.  Detection and characterization of placental microRNAs in maternal plasma. , 2008, Clinical chemistry.

[15]  X. Chen,et al.  Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases , 2008, Cell Research.

[16]  G. Bhanot,et al.  Identification of a microRNA panel for clear-cell kidney cancer. , 2010, Urology.

[17]  Ronald Simon,et al.  Bladder Cancer-associated Protein, a Potential Prognostic Biomarker in Human Bladder Cancer* , 2009, Molecular & Cellular Proteomics.

[18]  P. Albers,et al.  CpG island hypermethylation of cell-free circulating serum DNA in patients with testicular cancer. , 2009, The Journal of urology.

[19]  D. Ichikawa,et al.  Circulating microRNAs in plasma of patients with gastric cancers , 2010, British Journal of Cancer.

[20]  A. Jemal,et al.  Global cancer statistics , 2011, CA: a cancer journal for clinicians.

[21]  Holger Sültmann,et al.  Circulating miRNAs are correlated with tumor progression in prostate cancer , 2011, International journal of cancer.

[22]  J. Ellinger,et al.  Circulating microRNAs (miRNA) in serum of patients with prostate cancer. , 2011, Urology.

[23]  Michael J Kerin,et al.  Circulating microRNAs as Novel Minimally Invasive Biomarkers for Breast Cancer , 2010, Annals of surgery.

[24]  Jörg Grigull,et al.  miRNA profiling for clear cell renal cell carcinoma: biomarker discovery and identification of potential controls and consequences of miRNA dysregulation. , 2011, The Journal of urology.

[25]  Norbert Gretz,et al.  miRWalk - Database: Prediction of possible miRNA binding sites by "walking" the genes of three genomes , 2011, J. Biomed. Informatics.

[26]  R. Büttner,et al.  CpG Island hypermethylation in cell‐free serum DNA identifies patients with localized prostate cancer , 2008, The Prostate.

[27]  Hansjuerg Alder,et al.  The detection of differentially expressed microRNAs from the serum of ovarian cancer patients using a novel real-time PCR platform. , 2009, Gynecologic oncology.

[28]  Zhaohui Huang,et al.  Plasma microRNAs are promising novel biomarkers for early detection of colorectal cancer , 2010, International journal of cancer.

[29]  George A Calin,et al.  Micro-RNA profiling in kidney and bladder cancers. , 2007, Urologic oncology.

[30]  Y Dai,et al.  Microarray analysis of microRNA expression in renal clear cell carcinoma. , 2009, European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology.

[31]  Yurong Fu,et al.  Differential expression of miRNA patterns in renal cell carcinoma and nontumorous tissues , 2010, Journal of Cancer Research and Clinical Oncology.

[32]  R. Fimmers,et al.  Noncancerous PTGS2 DNA fragments of apoptotic origin in sera of prostate cancer patients qualify as diagnostic and prognostic indicators , 2008, International journal of cancer.