MicroRNAs as Potential Biomarkers for Diagnosing Cancers of Central Nervous System: a Meta-analysis
Recent studies have shown abnormal microRNA (miRNA) expression levels in the central nervous system (CNS) of cancer patients, suggesting that miRNAs may serve as promising biomarkers for cancers of CNS. However, other studies have arrived at conflicting results. Therefore, this meta-analysis aims to systematically measure the potential diagnostic value of miRNAs for CNS cancers. Electronic databases as well as other sources were searched until to April 12, 2014 for relevant articles. Data from different studies were pooled using the random-effects model. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative LR (NLR), diagnostic odds ratio (DOR), together with the summary receiver operator characteristic (SROC) curve, and area under the SROC curve (AUC) value were used to estimate overall diagnostic performance. Twenty-three studies from 6 articles were included in the current meta-analysis with a total of 299 CNS cancer patients and 418 controls. The pooled sensitivity, specificity, PLR, NLR, DOR, and AUC were 0.85 (95 % CI, 0.80–0.89), 0.83 (95 % CI, 0.76–0.88), 5.1 (95 % CI, 3.4–7.5), 0.18 (95 % CI, 0.12–0.26), 28 (95 % CI, 14–58), and 0.91 (95 % CI, 0.88–0.93), respectively. Subgroup analyses showed that cerebrospinal fluid (CSF)-based miRNAs assays yielded more accurate results and seemed to be more sensitive in diagnosing of primary central nervous system lymphoma (PCNSL). In conclusion, miRNAs may be suitable for serving as noninvasive biomarkers for CNS cancers detection. However, further validation based on a larger sample of patients and controls is still required.
KeywordsMicroRNAs Central nervous system cancers Diagnosis Meta-analysis
Sources of Funding
This work was funded by the National Nature Science Foundation of China (Numbers: 81372115, 81101504 and 31370834), a Foundation for the Author of National Excellent Doctoral Dissertation of PR China (Number: 201363).
Conflicts of Interest
The authors declare that they have no conflict of interest.
- 4.Pels H, Schmidt-Wolf IG, Glasmacher A, Schulz H, Engert A, Diehl V, Zellner A, Schackert G, Reichmann H, Kroschinsky F, Vogt-Schaden M, Egerer G, Bode U, Schaller C, Deckert M, Fimmers R, Helmstaedter C, Atasoy A, Klockgether T, Schlegel U (2003) Primary central nervous system lymphoma: results of a pilot and phase II study of systemic and intraventricular chemotherapy with deferred radiotherapy. J Clin Oncol Off J Am Soc Clin Oncol 21(24):4489–4495CrossRefGoogle Scholar
- 5.Tran B, Rosenthal MA (2010) Survival comparison between glioblastoma multiforme and other incurable cancers. J Clin Neurosci Off J Neurosurg Soc Australas 17(4):417–421Google Scholar
- 6.Stupp R, Hegi ME, Mason WP, van den Bent MJ, Taphoorn MJ, Janzer RC, Ludwin SK, Allgeier A, Fisher B, Belanger K, Hau P, Brandes AA, Gijtenbeek J, Marosi C, Vecht CJ, Mokhtari K, Wesseling P, Villa S, Eisenhauer E, Gorlia T, Weller M, Lacombe D, Cairncross JG, Mirimanoff RO (2009) Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol 10(5):459–466CrossRefPubMedGoogle Scholar
- 11.Baraniskin A, Kuhnhenn J, Schlegel U, Chan A, Deckert M, Gold R, Maghnouj A, Zollner H, Reinacher-Schick A, Schmiegel W, Hahn SA, Schroers R (2011) Identification of microRNAs in the cerebrospinal fluid as marker for primary diffuse large B-cell lymphoma of the central nervous system. Blood 117(11):3140–3146CrossRefPubMedGoogle Scholar
- 12.Schroers R, Baraniskin A, Heute C, Vorgerd M, Brunn A, Kuhnhenn J, Kowoll A, Alekseyev A, Schmiegel W, Schlegel U, Deckert M, Pels H (2010) Diagnosis of leptomeningeal disease in diffuse large B-cell lymphomas of the central nervous system by flow cytometry and cytopathology. Eur J Haematol 85(6):520–528CrossRefPubMedGoogle Scholar
- 14.Fischer L, Martus P, Weller M, Klasen HA, Rohden B, Roth A, Storek B, Hummel M, Nagele T, Thiel E, Korfel A (2008) Meningeal dissemination in primary CNS lymphoma: prospective evaluation of 282 patients. Neurology 71(14):1102–1108. doi: 10.1212/01.wnl.0000326958.52546.f5 CrossRefPubMedGoogle Scholar
- 15.Roy S, Josephson SA, Fridlyand J, Karch J, Kadoch C, Karrim J, Damon L, Treseler P, Kunwar S, Shuman MA, Jones T, Becker CH, Schulman H, Rubenstein JL (2008) Protein biomarker identification in the CSF of patients with CNS lymphoma. J Clin Oncol Off J Am Soc Clin Oncol 26(1):96–105CrossRefGoogle Scholar
- 26.Yang C, Wang C, Chen X, Chen S, Zhang Y, Zhi F, Wang J, Li L, Zhou X, Li N, Pan H, Zhang J, Zen K, Zhang CY, Zhang C (2013) Identification of seven serum microRNAs from a genome-wide serum microRNA expression profile as potential noninvasive biomarkers for malignant astrocytomas. Int J Cancer J Int Cancer 132(1):116–127CrossRefGoogle Scholar
- 28.Hu Z, Chen X, Zhao Y, Tian T, Jin G, Shu Y, Chen Y, Xu L, Zen K, Zhang C, Shen H (2010) Serum microRNA signatures identified in a genome-wide serum microRNA expression profiling predict survival of non-small-cell lung cancer. J Clin Oncol Off J Am Soc Clin Oncol 28(10):1721–1726CrossRefGoogle Scholar
- 29.Chen X, Ba Y, Ma L, Cai X, Yin Y, Wang K, Guo J, Zhang Y, Chen J, Guo X, Li Q, Li X, Wang W, Zhang Y, Wang J, Jiang X, Xiang Y, Xu C, Zheng P, Zhang J, Li R, Zhang H, Shang X, Gong T, Ning G, Wang J, Zen K, Zhang J, Zhang CY (2008) Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res 18(10):997–1006CrossRefPubMedGoogle Scholar
- 39.Puerta-Gil P, Garcia-Baquero R, Jia AY, Ocana S, Alvarez-Mugica M, Alvarez-Ossorio JL, Cordon-Cardo C, Cava F, Sanchez-Carbayo M (2012) miR-143, miR-222, and miR-452 are useful as tumor stratification and noninvasive diagnostic biomarkers for bladder cancer. Am J Pathol 180(5):1808–1815CrossRefPubMedGoogle Scholar
- 40.Piepoli A, Tavano F, Copetti M, Mazza T, Palumbo O, Panza A, di Mola FF, Pazienza V, Mazzoccoli G, Biscaglia G, Gentile A, Mastrodonato N, Carella M, Pellegrini F, di Sebastiano P, Andriulli A (2012) Mirna expression profiles identify drivers in colorectal and pancreatic cancers. PLoS One 7(3):e33663CrossRefPubMedCentralPubMedGoogle Scholar
- 42.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, Tewari M (2008) Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci U S A 105(30):10513–10518CrossRefPubMedCentralPubMedGoogle Scholar