Five miRNAs as Novel Diagnostic Biomarker Candidates for Primary Nasopharyngeal Carcinoma

  • Tang, Jin-Feng (Clinical Research Center, Guangdong Medical College) ;
  • Yu, Zhong-Hua (Department of Oncology, Affiliated Hospital of Guangdong Medical College) ;
  • Liu, Tie (Department of Hematology, the Second Affiliated Hospital, Medical School of Xi'an Jiaotong University) ;
  • Lin, Zi-Ying (Clinical Research Center, Guangdong Medical College) ;
  • Wang, Ya-Hong (Clinical Research Center, Guangdong Medical College) ;
  • Yang, La-Wei (Clinical Research Center, Guangdong Medical College) ;
  • He, Hui-Juan (Clinical Research Center, Guangdong Medical College) ;
  • Cao, Jun (Department of Pathology, Affiliated Hospital of Guangdong Medical College) ;
  • Huang, Hai-Li (Clinical Research Center, Guangdong Medical College) ;
  • Liu, Gang (Clinical Research Center, Guangdong Medical College)
  • Published : 2014.10.11


MicroRNAs (miRNAs) play an essential role in the development and progression of nasopharyngeal carcinomas (NPC). Despite advances in the field of cancer molecular biology and biomarker discovery, the development of clinically validated biomarkers for primary NPC has remained elusive. In this study, we investigated the expression and clinical significance of miRNAs as novel primary NPC diagnostic biomarkers. We used an array containing 2, 500 miRNAs to identify 22 significant miRNAs, and these candidate miRNAs were validated using 67 fresh NPC and 25 normal control tissues via quantitative real-time PCR (qRT-PCR). Expression and correlation analyses were performed with various statistical approaches, in addition to logistic regression and receiver operating characteristic curve analyses to evaluate diagnostic efficacy. qRT-PCR revealed five differentially expressed miRNAs (miR-93-5p, miR-135b-5p, miR-205-5p and miR-183-5p) in NPC tissue samples relative to control samples (p<0.05), with miR-135b-5p and miR-205-5p being of significant diagnostic value (p<0.01). Moreover, comparison of NPC patient clinicopathologic data revealed a negative correlation between miR-93-5p and miR-183-5p expression levels and lymph node status (p<0.05). These findings display an altered expression of many miRNAs in NPC tissues, thus providing information pertinent to pathophysiological and diagnostic research. Ultimately, miR-135b-5p and miR-205-5p may be implicated as novel NPC candidate biomarkers, while miR-93-5p, miR-650 and miR-183-5p may find application as relevant clinical pathology and diagnostic candidate biomarkers.


  1. Abbasi A N, Zahid S, Bhurgri Y, et al (2011). Nasopharyngeal carcinoma - an update of treatment and acute radiation induced reactions from a tertiary-care hospital in Pakistan. Asian Pac J Cancer Prev, 12, 735-8.
  2. Cao P, Zhou L, Zhang J, et al (2013). Comprehensive expression profiling of microRNAs in laryngeal squamous cell carcinoma. Head Neck, 35, 720-8.
  3. Chen H C, Chen G H, Chen Y H, et al (2009). MicroRNA deregulation and pathway alterations in nasopharyngeal carcinoma. Br J Cancer, 100, 1002-11.
  4. Fu X, Tian J, Zhang L, et al (2012). Involvement of microRNA-93, a new regulator of PTEN/Akt signaling pathway, in regulation of chemotherapeutic drug cisplatin chemosensitivity in ovarian cancer cells. FEBS Lett, 586, 1279-86.
  5. Jiang M, Zhang P, Hu G, et al (2013). Relative expressions of miR-205-5p, miR-205-3p, and miR-21 in tissues and serum of non-small cell lung cancer patients. Mol Cell Biochem, 383, 67-75.
  6. Guo X-G, Xia Y (2013). The interleukin-18 promoter-607C> A polymorphism contributes to nasopharyngeal carcinoma Risk: Evidence from a Meta-analysis Including 1, 886 Subjects. Asian Pac J Cancer Prev, 14, 7577-81.
  7. Iizasa H, Wulff BE, Alla NR, et al (2010). Editing of Epstein-Barr virus-encoded BART6 microRNAs controls their dicer targeting and consequently affects viral latency. J Biol Chem, 285, 33358-70.
  8. Iorio MV, Croce CM (2012). microRNA involvement in human cancer. Carcinogenesis, 33, 1126-33.
  9. Kozubek J, Ma Z, Fleming E, et al (2013). In-depth characterization of microRNA transcriptome in melanoma. PLoS One, 8, 72699.
  10. Larne O, Martens-Uzunova E, Hagman Z, et al (2013). miQ--a novel microRNA based diagnostic and prognostic tool for prostate cancer. Int J Cancer, 132, 2867-75.
  11. Lauvrak S U, Munthe E, Kresse S H, et al (2013). Functional characterisation of osteosarcoma cell lines and identification of mRNAs and miRNAs associated with aggressive cancer phenotypes. Br J Cancer, 109, 2228-36.
  12. Lebanony D, Benjamin H, Gilad S, et al (2009). Diagnostic assay based on hsa-miR-205 expression distinguishes squamous from nonsquamous non-small-cell lung carcinoma. J Clin Oncol, 27, 2030-7.
  13. Lee N, Xia P, Quivey J M, et al (2002). Intensity-modulated radiotherapy in the treatment of nasopharyngeal carcinoma: an update of the UCSF experience. Int J Radiat Oncol Biol Phys, 53, 12-22.
  14. Liu N, Chen N Y, Cui R X, et al (2012). Prognostic value of a microRNA signature in nasopharyngeal carcinoma: a microRNA expression analysis. Lancet Oncol, 13, 633-641.
  15. Li MY, Liu JQ, Chen DP, et al (2014). Glycididazole sodium combined with radiochemotherapy for locally advanced nasopharyngeal carcinoma. Asian Pac J Cancer Prev, 15, 2641.
  16. Li T, Chen J X, Fu X P, et al (2011). microRNA expression profiling of nasopharyngeal carcinoma. Oncol Rep, 25, 1353-63.
  17. Lin JC, Chiang CF, Wang SW, et al (2014). Significance of Expression of Human METCAM/MUC18 in Nasopharyngeal Carcinomas and Metastatic Lesions. Asian Pac J Cancer Prev, 15, 245-52.
  18. Liu N, Cui R X, Sun Y, et al (2014). A four-miRNA signature identified from genome-wide serum miRNA profiling predicts survival in patients with nasopharyngeal carcinoma. Int J Cancer, 134, 1359-68.
  19. Liu N, Tang L L, Sun Y, et al (2013a). MiR-29c suppresses invasion and metastasis by targeting TIAM1 in nasopharyngeal carcinoma. Cancer Lett, 329, 181-8.
  20. Liu X, Luo H N, Tian W D, et al (2013b). Diagnostic and prognostic value of plasma microRNA deregulation in nasopharyngeal carcinoma. Cancer Biol Ther, 14.
  21. Lo A K, Dawson C W, Jin D Y, et al (2012). The pathological roles of BART miRNAs in nasopharyngeal carcinoma. J Pathol, 227, 392-03.
  22. Long J, Wang Y, Wang W, et al (2010). Identification of microRNA-93 as a novel regulator of vascular endothelial growth factor in hyperglycemic conditions. J Biological Chemis, 285, 23457-65.
  23. Lu J, Getz G, Miska E A, et al (2005). MicroRNA expression profiles classify human cancers. Nature, 435, 834-8.
  24. Qiu J, Cosmopoulos K, Pegtel M, et al (2011). A novel persistence associated EBV miRNA expression profile is disrupted in neoplasia. PLoS Pathog, 7, 1002193.
  25. Luo W R, Gao F, Li S Y, et al (2012). Tumour budding and the expression of cancer stem cell marker aldehyde dehydrogenase 1 in nasopharyngeal carcinoma. Histopathology, 61, 1072-81.
  26. Ma F, Zhang J, Zhong L, et al (2014). Upregulated microRNA-301a in breast cancer promotes tumor metastasis by targeting PTEN and activating Wnt/beta-catenin signaling. Gene, 535, 191-7.
  27. Marquitz A R, Raab-Traub N (2012). The role of miRNAs and EBV BARTs in NPC. Semin Cancer Biol, 22, 166-72.
  28. Raab-Traub N, Flynn K, Pearson G, et al (1987). The differentiated form of nasopharyngeal carcinoma contains Epstein-Barr virus DNA. Int J Cancer, 39, 25-29.
  29. Sarver A L, Li L, Subramanian S (2010). MicroRNA miR-183 functions as an oncogene by targeting the transcription factor EGR1 and promoting tumor cell migration. Cancer Res, 70, 9570-80.
  30. Schetter A J, Harris C C (2011). Alterations of microRNAs contribute to colon carcinogenesis. Semin Oncol, 38, 734-72.
  31. Shanmugaratnam K, 1991, Histological typing of tumours of the upper respiratory tract and ear. World Health Organization International Histological Classification of Tumours. Springer-Verlag, Berlin, p. 32-34 pp.
  32. Sun XJ, Liu H, Zhang P, et al (2013). miR-10b promotes migration and invasion in nasopharyngeal carcinoma cells. Asian Pac J Cancer Prev, 14, 5533-37.
  33. Tsuchiyama K, Ito H, Taga M, et al (2013). Expression of microRNAs associated with Gleason grading system in prostate cancer: miR-182-5p is a useful marker for high grade prostate cancer. Prostate, 73, 827-34.
  34. Xie L, Yang Z, Li G, et al (2013). Genome-wide identification of bone metastasis-related microRNAs in lung adenocarcinoma by high-throughput sequencing. PLoS One, 8, 61212.
  35. Wolf H, Zur Hausen H, Klein G, et al (1975). Attempts to detect virus-specific DNA sequences in human tumors. III. Epstein-Barr viral DNA in non-lymphoid nasopharyngeal carcinoma cells. Med Microbiol Immunol, 161, 15-21.
  36. Xi Y, Nakajima G, Gavin E, et al (2007). Systematic analysis of microRNA expression of RNA extracted from fresh frozen and formalin-fixed paraffin-embedded samples. RNA, 13, 1668-74.
  37. Xiao Z G, Deng Z S, Zhang Y D, et al (2013). Clinical significance of microRNA-93 downregulation in human colon cancer. Eur J Gastroenterol Hepatol, 25, 296-01.
  38. Yang H J, Huang T J, Yang C F, et al (2013). Comprehensive profiling of Epstein-Barr virus-encoded miRNA species associated with specific latency types in tumor cells. Virol J, 10, 314.
  39. Yang I P, Tsai H L, Hou M F, et al (2012). MicroRNA-93 inhibits tumor growth and early relapse of human colorectal cancer by affecting genes involved in the cell cycle. Carcinogenesis, 33, 1522-30.
  40. Zheng G, Wang H, Zhang X, et al (2013). Identification and validation of reference genes for qPCR detection of serum microRNAs in colorectal adenocarcinoma patients. PLoS One, 8, 83025.
  41. Zhi F, Cao X, Xie X, et al (2013). Identification of circulating MicroRNAs as potential biomarkers for detecting acute myeloid leukemia. PloS one, 8, 56718.

Cited by

  1. MicroRNA-183 suppresses cancer stem-like cell properties in EBV-associated nasopharyngeal carcinoma vol.16, pp.1, 2016,
  2. MTUS1 and its targeting miRNAs in colorectal carcinoma: significant associations vol.37, pp.5, 2016,
  3. miR-183 and miR-21 expression as biomarkers of progression and survival in tongue carcinoma patients pp.1436-3771, 2017,
  4. Dynamic Changes in Plasma MicroRNAs Have Potential Predictive Values in Monitoring Recurrence and Metastasis of Nasopharyngeal Carcinoma vol.2018, pp.2314-6141, 2018,
  5. pp.1555-8576, 2018,
  6. Identification of four plasma microRNAs as potential biomarkers in the diagnosis of male lung squamous cell carcinoma patients in China vol.7, pp.6, 2018,
  7. Circulating MicroRNAs in Young Patients with Acute Coronary Syndrome vol.19, pp.5, 2018,
  8. A novel and non-invasive approach utilising nasal washings for the detection of nasopharyngeal carcinoma pp.00207136, 2019,