Circulating miR-17, miR-20a, miR-29c, and miR-223 Combined as Non-Invasive Biomarkers in Nasopharyngeal Carcinoma

Background MicroRNAs have been considered as a kind of potential novel biomarker for cancer detection due to their remarkable stability in the blood and the characteristics of their expression profile in many diseases. Methods We performed microarray-based serum miRNA profiling on the serum of twenty nasopharyngeal carcinoma patients at diagnosis along with 20 non-cancerous individuals as controls. This was followed by a real-time quantitative Polymerase Chain Reaction (RT-qPCR) in a separate cohort of thirty patients with nasopharyngeal carcinoma and thirty age- matched non-cancerous volunteers. A model for diagnosis was established by a conversion of mathematical calculation formula which has been validated by analyzing 74 cases of patients with nasopharyngeal carcinoma and 57 cases of non-cancerous volunteers. Results The profiles showed that 39 and 17 miRNAs are exclusively expressed in the serum of non-cancerous volunteers and of patients with nasopharyngeal carcinoma respectively. 4 miRNAs including miR-17, miR-20a, miR-29c, and miR-223 were found to be expressed differentially in the serum of NPC compared with that of non-cancerous control. Based on this, a diagnosis equation with Ct difference method has been established to distinguish NPC cases and non-cancerous controls and validated with high sensitivity and specificity. Conclusions We demonstrate that the serum miRNA-based biomarker model become a novel tool for NPC detection. The circulating 4-miRNA-based method may provide a novel strategy for NPC diagnosis.

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

[2]  Robin Foà,et al.  Gene expression profiling identifies a subset of adult T-cell acute lymphoblastic leukemia with myeloid-like gene features and over-expression of miR-223 , 2010, Haematologica.

[3]  J. Ju miRNAs as biomarkers in colorectal cancer diagnosis and prognosis. , 2010, Bioanalysis.

[4]  S. Baconnais,et al.  Extra-cellular release and blood diffusion of BART viral micro-RNAs produced by EBV-infected nasopharyngeal carcinoma cells , 2010, Virology Journal.

[5]  C. Croce,et al.  MicroRNAs in cancer: small molecules with a huge impact. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[6]  C. Croce,et al.  MicroRNA signatures in human cancers , 2006, Nature Reviews Cancer.

[7]  A. Rosenwald,et al.  MicroRNA expression, chromosomal alterations, and immunoglobulin variable heavy chain hypermutations in Mantle cell lymphomas. , 2009, Cancer research.

[8]  Ming-Yu Yang,et al.  Circulating miRNA is a novel marker for head and neck squamous cell carcinoma , 2012, Tumor Biology.

[9]  M. Mildner,et al.  miR-17, miR-19b, miR-20a, and miR-106a are down-regulated in human aging , 2010, Aging cell.

[10]  Xi Chen,et al.  Serum microRNA signatures identified in a genome-wide serum microRNA expression profiling predict survival of non-small-cell lung cancer. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[11]  Ying Sun,et al.  Prognostic value of a microRNA signature in nasopharyngeal carcinoma: a microRNA expression analysis. , 2012, The Lancet. Oncology.

[12]  Stephen P Finn,et al.  Potential role of miR-9 and miR-223 in recurrent ovarian cancer , 2008, Molecular Cancer.

[13]  Ying Tang,et al.  Repression of the miR‐17‐92 cluster by p53 has an important function in hypoxia‐induced apoptosis , 2009, The EMBO journal.

[14]  Peter Natesan Pushparaj,et al.  Oncomirs: The potential role of non-coding microRNAs in understanding cancer , 2008, Bioinformation.

[15]  Xi Chen,et al.  Identification of seven serum microRNAs from a genome‐wide serum microRNA expression profile as potential noninvasive biomarkers for malignant astrocytomas , 2013, International journal of cancer.

[16]  W. Tan,et al.  Circulating MicroRNAs, miR‐21, miR‐122, and miR‐223, in patients with hepatocellular carcinoma or chronic hepatitis , 2011, Molecular Carcinogenesis.

[17]  C. Muir,et al.  Nasopharyngeal carcinoma in non‐chinese populations with special reference to South‐East Asia and Africa , 1971, International journal of cancer.

[18]  Á. Zaballos,et al.  Vesicle-related microRNAs in plasma of nonsmall cell lung cancer patients and correlation with survival , 2010, European Respiratory Journal.

[19]  Jia-feng Wang,et al.  Serum miR-146a and miR-223 as potential new biomarkers for sepsis. , 2010, Biochemical and biophysical research communications.

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

[21]  Paul Ahlquist,et al.  MicroRNA 29c is down-regulated in nasopharyngeal carcinomas, up-regulating mRNAs encoding extracellular matrix proteins , 2008, Proceedings of the National Academy of Sciences.

[22]  Zhen-wu Zhang,et al.  [The roles of miR-17-92 cluster in mammal development and tumorigenesis]. , 2009, Yi chuan = Hereditas.

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

[24]  J. Ju,et al.  Impact of miRNAs in gastrointestinal cancer diagnosis and prognosis , 2010, Expert Reviews in Molecular Medicine.

[25]  Jin-Wu Nam,et al.  miR-29 miRNAs activate p53 by targeting p85α and CDC42 , 2009, Nature Structural &Molecular Biology.

[26]  Wen-Ling Liao,et al.  MicroRNA deregulation and pathway alterations in nasopharyngeal carcinoma , 2009, British Journal of Cancer.

[27]  Yuan Zhang,et al.  miR‐223 suppresses differentiation of tumor‐induced CD11b+Gr1+myeloid‐derived suppressor cells from bone marrow cells , 2011, International journal of cancer.

[28]  Wei Shi,et al.  Comprehensive MicroRNA Profiling for Head and Neck Squamous Cell Carcinomas , 2010, Clinical Cancer Research.

[29]  Chung-Wu Lin,et al.  E2A-positive gastric MALT lymphoma has weaker plasmacytoid infiltrates and stronger expression of the memory B-cell-associated miR-223: possible correlation with stage and treatment response , 2010, Modern Pathology.

[30]  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.

[31]  Patrick Maisonneuve,et al.  A serum circulating miRNA diagnostic test to identify asymptomatic high-risk individuals with early stage lung cancer , 2011, EMBO molecular medicine.

[32]  Ugo Pastorino,et al.  MicroRNA signatures in tissues and plasma predict development and prognosis of computed tomography detected lung cancer , 2011, Proceedings of the National Academy of Sciences.

[33]  M. Mayr,et al.  Plasma MicroRNA Profiling Reveals Loss of Endothelial MiR-126 and Other MicroRNAs in Type 2 Diabetes , 2010, Circulation research.

[34]  Gang Li,et al.  An in silico analysis of dynamic changes in microRNA expression profiles in stepwise development of nasopharyngeal carcinoma , 2012, BMC Medical Genomics.

[35]  D. Jin,et al.  The pathological roles of BART miRNAs in nasopharyngeal carcinoma , 2012, The Journal of pathology.

[36]  S. Fujieda,et al.  Epidemiological research into nasopharyngeal carcinoma in the Chubu region of Japan. , 1999, Auris, nasus, larynx.

[37]  Qinghua Zhou,et al.  miR-223 regulates migration and invasion by targeting Artemin in human esophageal carcinoma , 2011, Journal of Biomedical Science.

[38]  Massimo Negrini,et al.  Micromarkers: miRNAs in cancer diagnosis and prognosis , 2010, Expert review of molecular diagnostics.

[39]  Catalin Vasilescu,et al.  MicroRNA Fingerprints Identify miR-150 as a Plasma Prognostic Marker in Patients with Sepsis , 2009, PloS one.

[40]  Benjamin Haibe-Kains,et al.  microRNA-29c and microRNA-223 down-regulation has in vivo significance in chronic lymphocytic leukemia and improves disease risk stratification. , 2009, Blood.

[41]  Stefanie Dimmeler,et al.  The microRNA-17~92 cluster: Still a miRacle? , 2009, Cell cycle.

[42]  D. Kwong,et al.  Profiling of Epstein‐Barr virus‐encoded microRNAs in nasopharyngeal carcinoma reveals potential biomarkers and oncomirs , 2012, Cancer.

[43]  Š. Pospíšilová,et al.  MicroRNAs in chronic lymphocytic leukemia pathogenesis and disease subtypes , 2009, Leukemia & lymphoma.

[44]  T. Pabst,et al.  Complexity of miR-223 regulation by CEBPA in human AML. , 2010, Leukemia research.

[45]  Z. Zeng,et al.  Epstein-Barr Virus Downregulates MicroRNA 203 through the Oncoprotein Latent Membrane Protein 1: a Contribution to Increased Tumor Incidence in Epithelial Cells , 2011, Journal of Virology.

[46]  Chung-Wu Lin,et al.  Expression of CD19 and lack of miR‐223 distinguish extramedullary plasmacytoma from multiple myeloma , 2011, Histopathology.

[47]  Yariv Yogev,et al.  Serum MicroRNAs Are Promising Novel Biomarkers , 2008, PloS one.

[48]  Zhao-dian Chen,et al.  Up-regulation of microRNA in bladder tumor tissue is not common , 2010, International Urology and Nephrology.