Serum miR-210 as a potential biomarker of early clear cell renal cell carcinoma

Iwamoto,Hideto; Kanda,Yusuke; Sejima,Takehiro; Osaki,Mitsuhiko; Okada,Futoshi; Takenaka,Atsushi

doi:10.3892/ijo.2013.2169

Serum miR-210 as a potential biomarker of early clear cell renal cell carcinoma

Authors:
- Hideto Iwamoto
- Yusuke Kanda
- Takehiro Sejima
- Mitsuhiko Osaki
- Futoshi Okada
- Atsushi Takenaka
View Affiliations

Affiliations: Department of Surgery, Division of Urology, Faculty of Medicine, Tottori University, Tottori 683-8503, Japan, Department of Biomedical Sciences, Division of Pathological Biochemistry, Faculty of Medicine, Tottori University, Tottori 683-8503, Japan
Published online on: November 7, 2013 https://doi.org/10.3892/ijo.2013.2169
Pages: 53-58

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Early detection and treatment are critical in the management of renal cell carcinoma (RCC). However, there is no standard serum biomarker to facilitate early diagnosis or prognostic stratification in patients with RCC. Recent reports suggest that circulating microRNAs (miRNAs) have great potential as biomarkers for diagnosis and prognosis in patients with several types of cancers. Further, many studies using miRNA microarray analysis demonstrated that miR-210 expression in clear cell carcinoma (CCC), which is the largest subtype of RCC, was significantly upregulated in tumor tissue. Therefore, we investigated whether serum miR-210 could be a useful biomarker for the diagnosis and progression of CCC. This study included 34 CCC patients and 23 healthy controls (HC). First, we analyzed tissue miR-210 levels in tumor tissues and matched normal tissues from the 34 CCC patients. Second, we investigated the serum miR-210 levels in the 34 CCC patients and the 23 HC patients. Real-time polymerase chain reaction (PCR) was used to measure miRNA levels. Moreover, we examined the correlation between serum miR-210 levels and the clinicopathological parameters. Among patients with CCC, expression of miR-210 was higher in tumor tissues compared to normal tissues (P<0.001). Serum miR-210 levels were higher in CCC patients compared to HCs (P=0.001). Receiver operating characteristic (ROC) curve analysis showed an area under the ROC curve (AUC) of 0.77 (95% confidence interval, 0.65-0.89) and a sensitivity and specificity of 65 and 83%, respectively. In addition, there was no significant association between serum miR-210 levels and age, sex, tumor size or existence of metastasis at diagnosis among the 34 CCC patients. In conclusion, serum miR-210 upregulation may occur in the early stage of CCC and serum miR-210 can be a useful biomarker for early CCC in humans.

View Figures

View References

1.	Hollingsworth JM, Miller DC, Daignault S and Hollenbeck BK: Rising incidence of small renal masses: a need to reassess treatment effect. J Natl Cancer Inst. 98:1331–1334. 2006. View Article : Google Scholar : PubMed/NCBI
2.	Devita VT Jr, Hellman S and Rosenberg SA: Cancer Principles and Practice of Oncology. 8th edition. Lippincott Williams & Wilkins; 2008
3.	Ljungberg B, Cowan NC, Hanbury DC, Hora M, Kuczyk MA, Merseburger AS, Patard JJ, Mulders PF and Sinescu IC; European Association of Urology Guideline Group: EAU guidelines on renal cell carcinoma: the 2010 update. Eur Urol. 58:398–406. 2010. View Article : Google Scholar : PubMed/NCBI
4.	Slaby O, Jancovicova J, Lakomy R, Svoboda M, Poprach A, Fabian P, Kren L, Michalek J and Vyzula R: Expression of miRNA-106b in conventional renal cell carcinoma is a potential marker for prediction of early metastasis after nephrectomy. J Exp Clin Cancer Res. 29:902010. View Article : Google Scholar : PubMed/NCBI
5.	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 and Croce CM: A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci USA. 103:2257–2261. 2006. View Article : Google Scholar : PubMed/NCBI
6.	Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL, Peterson A, Noteboom J, O’Briant KC, Allen A, Lin DW, Urban N, Drescher CW, Knudsen BS, Stirewalt DL, Gentleman R, Vessella RL, Nelson PS, Martin DB and Tewari M: Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci USA. 105:10513–10518. 2008. View Article : Google Scholar : PubMed/NCBI
7.	Chim SS, Shing TK, Hung EC, Leung TY, Lau TK, Chiu RW and Lo YM: Detection and characterization of placental microRNAs in maternal plasma. Clin Chem. 54:482–490. 2008. View Article : Google Scholar : PubMed/NCBI
8.	Hunter MP, Ismail N, Zhang X, Aguda BD, Lee EJ, Yu L, Xiao T, Schafer J, Lee ML, Schmittgen TD, Nana-Sinkam SP, Jarjoura D and Marsh CB: Detection of microRNA expression in human peripheral blood microvesicles. PLoS One. 3:e36942008. View Article : Google Scholar : PubMed/NCBI
9.	Huang Z, Huang D, Ni S, Peng Z, Sheng W and Du X: Plasma microRNAs are promising novel biomarkers for early detection of colorectal cancer. Int J Cancer. 127:118–126. 2010. View Article : Google Scholar : PubMed/NCBI
10.	Roth C, Rack B, Müller V, Janni W, Pantel K and Schwarzenbach H: Circulating microRNAs as blood-based markers for patients with primary and metastatic breast cancer. Breast Cancer Res. 12:R902010. View Article : Google Scholar : PubMed/NCBI
11.	Nakada C, Tsukamoto Y, Matsuura K, Nguyen TL, Hijiya N, Uchida T, Sato F, Mimata H, Seto M and Moriyama M: Overexpression of miR-210, a downstream target of HIF1α, causes centrosome amplification in renal carcinoma cells. J Pathol. 224:280–288. 2011.PubMed/NCBI
12.	Crosby ME, Kulshreshtha R, Ivan M and Glazer PM: MicroRNA regulation of DNA repair gene expression in hypoxic stress. Cancer Res. 69:1221–1229. 2009. View Article : Google Scholar : PubMed/NCBI
13.	Fasanaro P, D’Alessandra Y, Di Stefano V, Melchionna R, Romani S, Pompilio G, Capogrossi MC and Martelli F: MicroRNA-210 modulates endothelial cell response to hypoxia and inhibits the receptor tyrosine kinase ligand Ephrin-A3. J Biol Chem. 283:15878–15883. 2008. View Article : Google Scholar : PubMed/NCBI
14.	Heneghan HM, Miller N, Lowery AJ, Sweeney KJ, Newell J and Kerin MJ: Circulating microRNAs as novel minimally invasive biomarkers for breast cancer. Ann Surg. 251:499–505. 2010. View Article : Google Scholar : PubMed/NCBI
15.	Tsujiura M, Ichikawa D, Komatsu S, Shiozaki A, Takeshita H, Kosuga T, Konishi H, Morimura R, Deguchi K, Fujiwara H, Okamoto K and Otsuji E: Circulating microRNAs in plasma of patients with gastric cancers. Br J Cancer. 102:1174–1179. 2010. View Article : Google Scholar : PubMed/NCBI
16.	Mahn R, Heukamp LC, Rogenhofer S, von Ruecker A, Müller SC and Ellinger J: Circulating microRNAs (miRNA) in serum of patients with prostate cancer. Urology. 77:1265.e9–16. 2011. View Article : Google Scholar : PubMed/NCBI
17.	Redova M, Svoboda M and Slaby O: MicroRNAs and their target gene networks in renal cell carcinoma. Biochem Biophys Res Commun. 405:153–156. 2011. View Article : Google Scholar : PubMed/NCBI
18.	White NM, Bao TT, Grigull J, Youssef YM, Girgis A, Diamandis M, Fatoohi E, Metias M, Honey RJ, Stewart R, Pace KT, Bjarnason GA and Yousef GM: miRNA profiling for clear cell renal cell carcinoma: biomarker discovery and identification of potential controls and consequences of miRNA dysregulation. J Urol. 186:1077–1083. 2011. View Article : Google Scholar : PubMed/NCBI
19.	Wotschofsky Z, Busch J, Jung M, Kempkensteffen C, Weikert S, Schaser KD, Melcher I, Kilic E, Miller K, Kristiansen G, Erbersdobler A and Jung K: Diagnostic and prognostic potential of differentially expressed miRNAs between metastatic and nonmetastatic renal cell carcinoma at the time of nephrectomy. Clin Chim Acta. 416:5–10. 2013. View Article : Google Scholar : PubMed/NCBI
20.	Wulfken LM, Moritz R, Ohlmann C, Holdenrieder S, Jung V, Becker F, Herrmann E, Walgenbach-Brünagel G, von Ruecker A, Müller SC and Ellinger J: MicroRNAs in renal cell carcinoma: diagnostic implications of serum miR-1233 levels. PLoS One. 6:e257872011. View Article : Google Scholar : PubMed/NCBI
21.	Redova M, Poprach A, Nekvindova J, Iliev R, Radova L, Lakomy R, Svoboda M, Vyzula R and Slaby O: Circulating miR-378 and miR-451 in serum are potential biomarkers for renal cell carcinoma. J Transl Med. 10:552012. View Article : Google Scholar : PubMed/NCBI
22.	Hauser S, Wulfken LM, Holdenrieder S, Moritz R, Ohlmann CH, Jung V, Becker F, Herrmann E, Walgenbach-Brünagel G, von Ruecker A, Müller SC and Ellinger J: Analysis of serum microRNAs (miR-26a-2^*, miR-191, miR-337-3p and miR-378) as potential biomarkers in renal cell carcinoma. Cancer Epidemiol. 36:391–394. 2012.
23.	Zhao A, Li G, Péoc’h M, Genin C and Gigante M: Serum miR-210 as a novel biomarker for molecular diagnosis of clear cell renal cell carcinoma. Exp Mol Pathol. 94:115–120. 2013. View Article : Google Scholar : PubMed/NCBI
24.	Kroh EM, Parkin RK, Mitchell PS and Tewari M: Analysis of circulating microRNA biomarkers in plasma and serum using quantitative reverse transcription-PCR (qRT-PCR). Methods. 50:298–301. 2010. View Article : Google Scholar : PubMed/NCBI
25.	Song J, Bai Z, Han W, Zhang J, Meng H, Bi J, Ma X, Han S and Zhang Z: Identification of suitable reference genes for qPCR analysis of serum microRNA in gastric cancer patients. Dig Dis Sci. 57:897–904. 2012. View Article : Google Scholar : PubMed/NCBI
26.	Cheng Y, Wang X, Yang J, Duan X, Yao Y, Shi X, Chen Z, Fan Z, Liu X, Qin S, Tang X and Zhang C: A translational study of urine miRNAs in acute myocardial infarction. J Mol Cell Cardiol. 53:668–676. 2012. View Article : Google Scholar : PubMed/NCBI
27.	Camps C, Buffa FM, Colella S, Moore J, Sotiriou C, Sheldon H, Harris AL, Gleadle JM and Ragoussis J: hsa-miR-210 is induced by hypoxia and is an independent prognostic factor in breast cancer. Clin Cancer Res. 14:1340–1348. 2008. View Article : Google Scholar : PubMed/NCBI
28.	Jung EJ, Santarpia L, Kim J, Esteva FJ, Moretti E, Buzdar AU, Di Leo A, Le XF, Bast RC Jr, Park ST, Pusztai L and Calin GA: Plasma microRNA 210 levels correlate with sensitivity to trastuzumab and tumor presence in breast cancer patients. Cancer. 118:2603–2614. 2012. View Article : Google Scholar : PubMed/NCBI
29.	Eble JN, Sauter G, Epstein JI and Sesterhenn IA: World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of the Urinary System and Male Genital Organs. IARC Press; Lyon: pp. 9–87. 2004