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

被引:193
作者
Wulfken, Lena M. [1 ]
Moritz, Rudolf [2 ]
Ohlmann, Carsten [3 ]
Holdenrieder, Stefan [4 ]
Jung, Volker [3 ]
Becker, Frank [3 ]
Herrmann, Edwin [2 ]
Walgenbach-Bruenagel, Gisela
von Ruecker, Alexander [5 ]
Mueller, Stefan C. [1 ]
Ellinger, Joerg [1 ]
机构
[1] Univ Klinikum Bonn, Klin & Poliklin Urol & Kinderurol, Bonn, Germany
[2] Univ Klinikum Munster, Klin & Poliklin Urol, Munster, Germany
[3] Univ Klinikum Saarlandes, Klin & Poliklin Urol, Homburg, Germany
[4] Univ Klinikum Bonn, Inst Klin Chem & Klin Pharmakol, Bonn, Germany
[5] Univ Klinikum Bonn, Inst Pathol, Bonn, Germany
来源
PLOS ONE | 2011年 / 6卷 / 09期
关键词
CIRCULATING MICRORNAS; CANCER; BIOMARKERS; EXPRESSION; KIDNEY; PLASMA; HYPERMETHYLATION; IDENTIFICATION;
D O I
10.1371/journal.pone.0025787
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
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页数:7
相关论文
共 32 条
[21]   Circulating microRNAs (miRNA) in Serum of Patients With Prostate Cancer [J].
Mahn, Robert ;
Heukamp, Lukas C. ;
Rogenhofer, Sebastian ;
von Ruecker, Alexander ;
Mueller, Stefan C. ;
Ellinger, Joerg .
UROLOGY, 2011, 77 (05) :1265.e9-1265.e16
[22]   Circulating microRNAs as stable blood-based markers for cancer detection [J].
Mitchell, Patrick S. ;
Parkin, Rachael K. ;
Kroh, Evan M. ;
Fritz, Brian R. ;
Wyman, Stacia K. ;
Pogosova-Agadjanyan, Era L. ;
Peterson, Amelia ;
Noteboom, Jennifer ;
O'Briant, Kathy C. ;
Allen, April ;
Lin, Daniel W. ;
Urban, Nicole ;
Drescher, Charles W. ;
Knudsen, Beatrice S. ;
Stirewalt, Derek L. ;
Gentleman, Robert ;
Vessella, Robert L. ;
Nelson, Peter S. ;
Martin, Daniel B. ;
Tewari, Muneesh .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (30) :10513-10518
[23]   Bladder Cancer-associated Protein, a Potential Prognostic Biomarker in Human Bladder Cancer [J].
Moreira, Jose M. A. ;
Ohlsson, Gita ;
Gromov, Pavel ;
Simon, Ronald ;
Sauter, Guido ;
Celis, Julio E. ;
Gromova, Irina .
MOLECULAR & CELLULAR PROTEOMICS, 2010, 9 (01) :161-177
[24]   Genome-wide microRNA expression profiling in renal cell carcinoma: significant down-regulation of miR-141 and miR-200c [J].
Nakada, C. ;
Matsuura, K. ;
Tsukamoto, Y. ;
Tanigawa, M. ;
Yoshimoto, T. ;
Narimatsu, T. ;
Nguyen, L. T. ;
Hijiya, N. ;
Uchida, T. ;
Sato, F. ;
Mimata, H. ;
Seto, M. ;
Moriyama, M. .
JOURNAL OF PATHOLOGY, 2008, 216 (04) :418-427
[25]   Differential expression of microRNAs in plasma of patients with colorectal cancer: a potential marker for colorectal cancer screening [J].
Ng, E. K. O. ;
Chong, W. W. S. ;
Jin, H. ;
Lam, E. K. Y. ;
Shin, V. Y. ;
Yu, J. ;
Poon, T. C. W. ;
Ng, S. S. M. ;
Sung, J. J. Y. .
GUT, 2009, 58 (10) :1375-1381
[26]   MicroRNA profiling of human kidney cancer subtypes [J].
Petillo, David ;
Kort, Eric J. ;
Anema, John ;
Furge, Kyle A. ;
Yang, Ximing J. ;
Teh, Bin Tean .
INTERNATIONAL JOURNAL OF ONCOLOGY, 2009, 35 (01) :109-114
[27]   The detection of differentially expressed microRNAs from the serum of ovarian cancer patients using a novel real-time PCR platform [J].
Resnick, Kimberly E. ;
Alder, Hansjuerg ;
Hagan, John P. ;
Richardson, Debra L. ;
Croce, Carlo M. ;
Cohn, David E. .
GYNECOLOGIC ONCOLOGY, 2009, 112 (01) :55-59
[28]   Circulating microRNAs in plasma of patients with gastric cancers [J].
Tsujiura, M. ;
Ichikawa, D. ;
Komatsu, S. ;
Shiozaki, A. ;
Takeshita, H. ;
Kosuga, T. ;
Konishi, H. ;
Morimura, R. ;
Deguchi, K. ;
Fujiwara, H. ;
Okamoto, K. ;
Otsuji, E. .
BRITISH JOURNAL OF CANCER, 2010, 102 (07) :1174-1179
[29]   A microRNA expression signature of human solid tumors defines cancer gene targets [J].
Volinia, S ;
Calin, GA ;
Liu, CG ;
Ambs, S ;
Cimmino, A ;
Petrocca, F ;
Visone, R ;
Iorio, M ;
Roldo, C ;
Ferracin, M ;
Prueitt, RL ;
Yanaihara, N ;
Lanza, G ;
Scarpa, A ;
Vecchione, A ;
Negrini, M ;
Harris, CC ;
Croce, CM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (07) :2257-2261
[30]   miRNA Profiling for Clear Cell Renal Cell Carcinoma: Biomarker Discovery and Identification of Potential Controls and Consequences of miRNA Dysregulation [J].
White, Nicole M. A. ;
Bao, Tian Tian ;
Grigull, Joerg ;
Youssef, Youssef M. ;
Girgis, Andrew ;
Diamandis, Maria ;
Fatoohi, Eman ;
Metias, Maged ;
Honey, R. John ;
Stewart, Robert ;
Pace, Kenneth T. ;
Bjarnason, Georg A. ;
Yousef, George M. .
JOURNAL OF UROLOGY, 2011, 186 (03) :1077-1083