Review Serum microRNAs as powerful cancer biomarkers Jürgen Wittmann ⁎, Hans-Martin Jäck Division of Molecular Immunology, Department of Internal Medicine III, Nikolaus-Fiebiger-Center, University of Erlangen-Nürnberg, D-91054 Erlangen, Germany abstract article info Article history: Received 24 April 2010 Accepted 7 July 2010 Available online 13 July 2010 Keywords: MicroRNA Serum Biomarker Exosome Cancer MicroRNAs (miRNAs) are a class of small non-coding RNAs that regulate gene expression at the posttranscriptional level by either degrading or blocking translation of messenger RNA targets. Recent expression profiling studies have revealed that miRNAs play important regulatory roles in a variety of cellular functions as well as in every cancer type studied so far. Lately, the discovery of miRNAs in the serum of cancer patients opened up the exciting prospective of using miRNAs as powerful and non-invasive cancer biomarkers. In this article, we review the current literature on serum miRNAs in different cancer types and the approaches used to detect and quantify these molecules. We then discuss the potential of miRNA biomarkers to improve disease diagnosis by distinguishing healthy from malignant tissues, identifying the tissue of origin in poorly differentiated tumors or tumors of unknown origin and distinguishing between different subtypes of the same tumor. We will also compare the advantages and disadvantages of potential serum miRNA biomarker molecules for cancer classification, estimation of prognosis and prediction of therapeutic efficacy. Finally, we will establish a set of criteria that these new molecules and clinical studies that use them must fulfill before they can be used as reliable tools in diagnostic and prognostic settings. © 2010 Elsevier B.V. All rights reserved. Contents 1. Cancer biomarkers and miRNAs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 200 2. Introduction to exosomes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 201 3. Serum miRNAs as potential cancer biomarkers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 202 3.1. Serum miRNAs in lymphoma, acute leukemia and glioblastoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 202 3.2. Serum miRNAs in gastric, colorectal and lung cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 203 3.3. Serum miRNAs in oral and squamous cell cancer. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 204 3.4. Serum miRNAs in breast cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 204 3.5. Serum miRNAs in ovarian cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 204 3.6. Serum miRNAs in prostate cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 204 3.7. Serum miRNAs in pancreatic and hepatocellular cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 205 4. Points to consider when using serum miRNAs as biomarkers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 205 Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 206 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 206 1. Cancer biomarkers and miRNAs After cardiovascular and infectious diseases, cancer-related mor- tality is the third-most common cause of death worldwide. Cancer development involves the complex and progressive accumulation of a number of molecular changes, such as point mutations, loss of heterozygosity, viral genomic integration and epigenetic alterations. Uncontrolled cell growth, tissue invasion and metastasis distinguish benign from malign tumors. One of the biggest challenges in cancer treatment, yet still the most effective treatment, is to detect cancer at an early stage and, ideally, find the means to predict who will develop Biochimica et Biophysica Acta 1806 (2010) 200–207 Abbreviations: AFP, alpha-fetoprotein; ALL, acute lymphoblastic leukemia; ALT, alanine aminotransferase; AML, acute myeloid leukemia; CRP, C-reactive protein; DLBCL, diffuse large B-cell lymphoma; EpCAM, epithelial cell adhesion molecule; GC, gastric cancer; ER, estrogen receptor; HCC, hepatocellular carcinoma; MACS, magnetic activated cell sorting; miRNA, microRNA; NSCLC, non-small-cell lung cancer; OSCC, oral squamous cell carcinoma; PBMC, peripheral blood mononuclear cells; qRT-PCR, quantitative RT-PCR; RISC, RNA-induced silencing complex; SAGE, serial analysis of gene expression ⁎ Corresponding author. Division of Molecular Immunology, Nikolaus-Fiebiger-Center, University of Erlangen-Nürnberg, Glückstr. 6, D-91054 Erlangen, Germany. Tel.: +49 9131 8539105; fax: +49 9131 8539343. E-mail address: jwittman@molmed.uni-erlangen.de (J. Wittmann). 0304-419X/$ – see front matter © 2010 Elsevier B.V. All rights reserved. doi:10.1016/j.bbcan.2010.07.002 Contents lists available at ScienceDirect Biochimica et Biophysica Acta journal homepage: www.elsevier.com/locate/bbacan