Tumor Biology

, Volume 36, Issue 3, pp 1993–2005 | Cite as

The clinical utility of microRNA-21 as novel biomarker for diagnosing human cancers

  • Lijun Shen
  • Zhihong Wan
  • Yuming Ma
  • Libing Wu
  • Fangfang Liu
  • Hong Zang
  • Shaojie Xin
Research Article


With cancer being a major cause of death worldwide, microRNAs (miRNAs) have been investigated as novel and non-invasive biomarkers for cancer diagnosis. Recently, microRNA-21 (miR-21) attracts much attention for its aberrant expression and has been widely studied in various cancers. However, the inconsistent results from studies make it hard to evaluate the diagnostic value of miR-21 in cancer diagnosis, which lead us to conduct this meta-analysis. We conducted a comprehensive literature search in the Medline, Embase, PubMed, CNKI, and Web of Science before July 1, 2014. STATA 12.0 software was used for calculation and statistical analysis. The pooled sensitivity, specificity, positive and negative likelihood ratio (PLR, NLR), and diagnostic odds ratio (DOR) were used to assess the diagnostic performance of miR-21 for cancers. Seventy-three studies in 60 articles were involved in this meta-analysis, with a total of 4684 patients with cancer and 3108 controls. The overall parameters were calculated from all the included studies: sensitivity of 0.78 (95 % confidence interval (CI) 0.74–0.81), specificity of 0.83 (95 % CI 0.80–0.86), PLR of 4.5 (95 % CI 3.8–5.4), NLR of 0.27 (95 % CI 0.23–0.32); DOR of 17 (95 % CI 12–23), and area under the curve (AUC) of 0.88 (95 % CI 0.84–0.90). In addition, we performed subgroup analyses based on ethnicity, cancer types, and sample types. Results from subgroup analysis showed that cancer types and sample types were the sources of heterogeneity in our meta-analysis. The overall diagnostic value of miR-21 is not very high for cancer diagnosis; however, it is affected significantly by the types of cancer and specimen. MiR-21 has a relatively high diagnostic value for detecting breast cancer, and miR-21 assays based on plasma, serum, and tissue achieved relatively higher accuracy.


Cancer MicroRNA-21 Blood Tissue Sputum Diagnosis Meta-analysis 



This work was supported by the National 12th Five-Year Special Grand Project for Infectious Diseases (2012ZX10002004-005).

Conflicts of interest



  1. 1.
    Chan SH, Wu CW, Li AF, Chi CW, Lin WC. miR-21 microRNA expression in human gastric carcinomas and its clinical association. Anticancer Res. 2008;28:907–11.PubMedGoogle Scholar
  2. 2.
    Chen X, Ba Y, Ma L, Cai X, Yin Y, Wang K, et al. Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res. 2008;18:997–1006. doi: 10.1038/cr.2008.282.CrossRefPubMedGoogle Scholar
  3. 3.
    Bhardwaj A, Arora S, Prajapati VK, Singh S, Singh AP. Cancer “stemness”-regulating microRNAs: role, mechanisms and therapeutic potential. Curr Drug Targets. 2013;14:1175–84.CrossRefPubMedGoogle Scholar
  4. 4.
    Breitkreutz D, Hlatky L, Rietman E, Tuszynski JA. Molecular signaling network complexity is correlated with cancer patient survivability. Proc Natl Acad Sci U S A. 2012;109:9209–12. doi: 10.1073/pnas.1201416109.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Wang Q, Wu X, Wu T, Li GM, Shi Y. Clinical significance of RKIP mRNA expression in non-small cell lung cancer. Tumour Biol. 2014;35:4377–80. doi: 10.1007/s13277-013-1575-4.CrossRefPubMedGoogle Scholar
  6. 6.
    Tran B, Rosenthal MA. Survival comparison between glioblastoma multiforme and other incurable cancers. J Clin Neurosci. 2010;17:417–21. doi: 10.1016/j.jocn.2009.09.004.CrossRefPubMedGoogle Scholar
  7. 7.
    El-Serag HB, Rudolph KL. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology. 2007;132:2557–76. doi: 10.1053/j.gastro.2007.04.061.CrossRefPubMedGoogle Scholar
  8. 8.
    Song MY, Pan KF, Su HJ, Zhang L, Ma JL, Li JY, et al. Identification of serum microRNAs as novel non-invasive biomarkers for early detection of gastric cancer. PLoS ONE. 2012;7:e33608. doi: 10.1371/journal.pone.0033608.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90. doi: 10.3322/caac.20107.CrossRefPubMedGoogle Scholar
  10. 10.
    O’Byrne KJ, Gatzemeier U, Bondarenko I, Barrios C, Eschbach C, Martens UM, et al. Molecular biomarkers in non-small-cell lung cancer: a retrospective analysis of data from the phase 3 FLEX study. Lancet Oncol. 2011;12:795–805. doi: 10.1016/S1470-2045(11)70189-9.CrossRefPubMedGoogle Scholar
  11. 11.
    Mar-Aguilar F, Mendoza-Ramirez JA, Malagon-Santiago I, Espino-Silva PK, Santuario-Facio SK, Ruiz-Flores P, et al. Serum circulating microRNA profiling for identification of potential breast cancer biomarkers. Dis Markers. 2013;34:163–9. doi: 10.3233/dma-120957.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Yang X, Guo Y, Du Y, Yang J, Li S, Liu S, et al. Serum microRNA-21 as a diagnostic marker for lung carcinoma: a systematic review and meta-analysis. PLoS One. 2014;9:e97460. doi: 10.1371/journal.pone.0097460.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Reitsma JB, Glas AS, Rutjes AW, Scholten RJ, Bossuyt PM, Zwinderman AH. Bivariate analysis of sensitivity and specificity produces informative summary measures in diagnostic reviews. J Clin Epidemiol. 2005;58:982–90. doi: 10.1016/j.jclinepi.2005.02.022.CrossRefPubMedGoogle Scholar
  14. 14.
    Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin. 2014;64:9–29. doi: 10.3322/caac.21208.CrossRefPubMedGoogle Scholar
  15. 15.
    Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin. 2013;63:11–30.CrossRefPubMedGoogle Scholar
  16. 16.
    Bentwich I, Avniel A, Karov Y, Aharonov R, Gilad S, Barad O, et al. Identification of hundreds of conserved and nonconserved human microRNAs. Nat Genet. 2005;37:766–70. doi: 10.1038/ng1590.CrossRefPubMedGoogle Scholar
  17. 17.
    Whiting PF, Rutjes AW, Westwood ME, Mallett S, Deeks JJ, Reitsma JB, et al. QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Ann Intern Med. 2011;155:529–36. doi: 10.7326/0003-4819-155-8-201110180-00009.CrossRefPubMedGoogle Scholar
  18. 18.
    Wu R, Jiang Y, Wu Q, Li Q, Cheng D, Xu L, et al. Diagnostic value of microRNA-21 in the diagnosis of lung cancer: evidence from a meta-analysis involving 11 studies. Tumour Biol. 2014. doi: 10.1007/s13277-014-2106-7.Google Scholar
  19. 19.
    Wang Y, Gao X, Wei F, Zhang X, Yu J, Zhao H, et al. Diagnostic and prognostic value of circulating miR-21 for cancer: a systematic review and meta-analysis. Gene. 2014;533:389–97. doi: 10.1016/j.gene.2013.09.038.CrossRefPubMedGoogle Scholar
  20. 20.
    Yu L, Todd NW, Xing L, Xie Y, Zhang H, Liu Z, et al. Early detection of lung adenocarcinoma in sputum by a panel of microRNA markers. Int J Cancer. 2010;127:2870–8. doi: 10.1002/ijc.25289.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Zeng Z, Wang J, Zhao L, Hu P, Zhang H, Tang X, et al. Potential role of microRNA-21 in the diagnosis of gastric cancer: a meta-analysis. PLoS One. 2013;8:e73278. doi: 10.1371/journal.pone.0073278.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Zhang B, Wang Q, Pan X. MicroRNAs and their regulatory roles in animals and plants. J Cell Physiol. 2007;210:279–89. doi: 10.1002/jcp.20869.CrossRefPubMedGoogle Scholar
  23. 23.
    Hamza TH, Arends LR, van Houwelingen HC, Stijnen T. Multivariate random effects meta-analysis of diagnostic tests with multiple thresholds. BMC Med Res Methodol. 2009;9:73. doi: 10.1186/1471-2288-9-73.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Xie H, Chu Z, Wang H. Serum microRNA expression profile as a biomarker in diagnosis and prognosis of acute myeloid leukemia. J Clin Pediatr. 2012;30:421–4.Google Scholar
  25. 25.
    Kishimoto T, Eguchi H, Nagano H, Kobayashi S, Akita H, Hama N, et al. Plasma miR-21 is a novel diagnostic biomarker for biliary tract cancer. Cancer Sci. 2013;104:1626–31. doi: 10.1111/cas.12300.CrossRefPubMedGoogle Scholar
  26. 26.
    Zaravinos A, Radojicic J, Lambrou GI, Volanis D, Delakas D, Stathopoulos EN, et al. Expression of miRNAs involved in angiogenesis, tumor cell proliferation, tumor suppressor inhibition, epithelial-mesenchymal transition and activation of metastasis in bladder cancer. J Urol. 2012;188:615–23. doi: 10.1016/j.juro.2012.03.122.CrossRefPubMedGoogle Scholar
  27. 27.
    Asaga S, Kuo C, Nguyen T, Terpenning M, Giuliano AE, Hoon DS. Direct serum assay for microRNA-21 concentrations in early and advanced breast cancer. Clin Chem. 2011;57:84–91. doi: 10.1373/clinchem.2010.151845.CrossRefPubMedGoogle Scholar
  28. 28.
    Gao J, Zhang Q, Xu J, Guo L, Li X. Clinical significance of serum miR-21 in breast cancer compared with CA153 and CEA. Chin J Cancer Res. 2013;25:743–8. doi: 10.3978/j.issn. 1000-9604.2013.12.04.PubMedPubMedCentralGoogle Scholar
  29. 29.
    Lee CH, Kuo WH, Lin CC, Oyang YJ, Huang HC, Juan HF. MicroRNA-regulated protein-protein interaction networks and their functions in breast cancer. Int J Mol Sci. 2013;14:11560–606. doi: 10.3390/ijms140611560.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Mar-Aguilar F, Luna-Aguirre CM, Moreno-Rocha JC, Araiza-Chavez J, Trevino V, Rodriguez-Padilla C, et al. Differential expression of miR-21, miR-125b and miR-191 in breast cancer tissue. Asia Pac J Clin Oncol. 2013;9:53–9. doi: 10.1111/j.1743-7563.2012.01548.x.CrossRefPubMedGoogle Scholar
  31. 31.
    Ng EK, Li R, Shin VY, Jin HC, Leung CP, Ma ES, et al. Circulating microRNAs as specific biomarkers for breast cancer detection. PLoS One. 2013;8:e53141. doi: 10.1371/journal.pone.0053141.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Wang B, Zhang Q. The expression and clinical significance of circulating microRNA-21 in serum of five solid tumors. J Cancer Res Clin Oncol. 2012;138:1659–66. doi: 10.1007/s00432-012-1244-9.CrossRefPubMedGoogle Scholar
  33. 33.
    Selaru FM, Olaru AV, Kan T, David S, Cheng Y, Mori Y, et al. MicroRNA-21 is overexpressed in human cholangiocarcinoma and regulates programmed cell death 4 and tissue inhibitor of metalloproteinase 3. Hepatology. 2009;49:1595–601. doi: 10.1002/hep.22838.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Kanaan Z, Rai SN, Eichenberger MR, Roberts H, Keskey B, Pan J, et al. Plasma MiR-21: A potential diagnostic marker of colorectal cancer. Ann Surg. 2012;256:544–51.CrossRefPubMedGoogle Scholar
  35. 35.
    Koga Y, Yasunaga M, Takahashi A, Kuroda J, Moriya Y, Akasu T, et al. MicroRNA expression profiling of exfoliated colonocytes isolated from feces for colorectal cancer screening. Cancer Prev Res. 2010;3:1435–42.CrossRefGoogle Scholar
  36. 36.
    Kuriyama S, Hamaya Y, Yamada T, Sugimoto M, Osawa S, Sugimoto K, et al. Fecal microrna assays as a marker for colorectal cancer screening. Gastroenterology. 2012;142:S770.CrossRefGoogle Scholar
  37. 37.
    Liu GH, Zhou ZG, Chen R, Wang MJ, Zhou B, Li Y, et al. Serum miR-21 and miR-92a as biomarkers in the diagnosis and prognosis of colorectal cancer. Tumour Biol. 2013;34:2175–81. doi: 10.1007/s13277-013-0753-8.CrossRefPubMedGoogle Scholar
  38. 38.
    Luo X, Stock C, Burwinkel B, Brenner H. Identification and evaluation of plasma microRNAs for early detection of colorectal cancer. PLoS ONE. 2013;8:e62880. doi: 10.1371/journal.pone.0062880.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Toiyama Y, Takahashi M, Hur K, Nagasaka T, Tanaka K, Inoue Y, et al. Serum miR-21 as a diagnostic and prognostic biomarker in colorectal cancer. J Natl Cancer Inst. 2013;105:849–59.CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Wu CW, Ng SSM, Dong YJ, Ng SC, Leung WW, Lee CW, et al. Detection of miR-92a and miR-21 in stool samples as potential screening biomarkers for colorectal cancer and polyps. Gut. 2012;61:739–45.CrossRefPubMedGoogle Scholar
  41. 41.
    Zanutto S, Pizzamiglio S, Ghilotti M, Bertan C, Ravagnani F, Perrone F, et al. Circulating miR-378 in plasma: a reliable, haemolysis-independent biomarker for colorectal cancer. Br J Cancer. 2014;110:1001–7. doi: 10.1038/bjc.2013.819.CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Xie ZJ, Chen G, Zhang XC, Li DF, Huang J, Li ZJ. Saliva supernatant miR-21: a novel potential biomarker for esophageal cancer detection. Asian Pac J Cancer Prev. 2012;13:6145–9.CrossRefPubMedGoogle Scholar
  43. 43.
    Ye M, Ye P, Zhang W, Rao J, Xie Z. Diagnostic values of salivary versus and plasma microRNA-21 for early esophageal cancer. Nan Fang Yi Ke Da Xue Xue Bao. 2014;34:885–9.PubMedGoogle Scholar
  44. 44.
    Cui L, Zhang X, Ye G, Zheng T, Song H, Deng H, et al. Gastric juice MicroRNAs as potential biomarkers for the screening of gastric cancer. Cancer. 2013;119:1618–26. doi: 10.1002/cncr.27903.CrossRefPubMedGoogle Scholar
  45. 45.
    Li BS, Zhao YL, Guo G, Li W, Zhu ED, Luo X, et al. Plasma microRNAs, miR-223, miR-21 and miR-218, as novel potential biomarkers for gastric cancer detection. PLoS One. 2012;7:e41629. doi: 10.1371/journal.pone.0041629.CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Shiotani A, Murao T, Kimura Y, Matsumoto H, Kamada T, Kusunoki H, et al. Identification of serum miRNAs as novel non-invasive biomarkers for detection of high risk for early gastric cancer. Br J Cancer. 2013;109:2323–30. doi: 10.1038/bjc.2013.596.CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Zheng Y, Cui L, Sun W, Zhou H, Yuan X, Huo M, et al. MicroRNA-21 is a new marker of circulating tumor cells in gastric cancer patients. Cancer Biomark. 2011;10:71–7. doi: 10.3233/cbm-2011-0231.CrossRefPubMedGoogle Scholar
  48. 48.
    Akers JC, Ramakrishnan V, Kim R, Skog J, Nakano I, Pingle S, et al. MiR-21 in the extracellular vesicles (EVs) of cerebrospinal fluid (CSF): a platform for glioblastoma biomarker development. PLoS ONE. 2013;8:e78115. doi: 10.1371/journal.pone.0078115.CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Wang F, Sun GP, Zou YF, Hao JQ, Zhong F, Ren WJ. MicroRNAs as promising biomarkers for gastric cancer. Cancer Biomark. 2012;11:259–67. doi: 10.3233/cbm-2012-00284.CrossRefPubMedGoogle Scholar
  50. 50.
    Liu AM, Yao TJ, Wang W, Wong KF, Lee NP, Fan ST, et al. Circulating miR-15b and miR-130b in serum as potential markers for detecting hepatocellular carcinoma: a retrospective cohort study. BMJ Open. 2012;2:e000825. doi: 10.1136/bmjopen-2012-000825.CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Qin Z, Zhu X, Huang Y. Circulating microRNA-21 as a novel biomarker for hepatocellular carcinoma. SiChuan Med J. 2013;34:1463–5.Google Scholar
  52. 52.
    Tomimaru Y, Eguchi H, Nagano H, Wada H, Kobayashi S, Marubashi S, et al. Circulating microRNA-21 as a novel biomarker for hepatocellular carcinoma. J Hepatol. 2012;56:167–75. doi: 10.1016/j.jhep.2011.04.026.CrossRefPubMedGoogle Scholar
  53. 53.
    Xu J, Wu C, Che X, Wang L, Yu D, Zhang T, et al. Circulating microRNAs, miR-21, miR-122, and miR-223, in patients with hepatocellular carcinoma or chronic hepatitis. Mol Carcinog. 2011;50:136–42. doi: 10.1002/mc.20712.CrossRefPubMedGoogle Scholar
  54. 54.
    Abd-El-Fattah AA, Sadik NA, Shaker OG, Aboulftouh ML. Differential microRNAs expression in serum of patients with lung cancer, pulmonary tuberculosis, and pneumonia. Cell Biochem Biophys. 2013;67:875–84. doi: 10.1007/s12013-013-9575-y.CrossRefPubMedGoogle Scholar
  55. 55.
    Le HB, Zhu WY, Chen DD, He JY, Huang YY, Liu XG, et al. Evaluation of dynamic change of serum miR-21 and miR-24 in pre- and post-operative lung carcinoma patients. Med Oncol. 2012;29:3190–7. doi: 10.1007/s12032-012-0303-z.CrossRefPubMedGoogle Scholar
  56. 56.
    Li Y, Li W, Ouyang Q, Hu S, Tang J. Detection of lung cancer with blood microRNA-21 expression levels in Chinese population. Oncol Lett. 2011;2:991–4. doi: 10.3892/ol.2011.351.PubMedPubMedCentralGoogle Scholar
  57. 57.
    Ma J, Li N, Guarnera M, Jiang F. Quantification of plasma miRNAs by digital PCR for cancer diagnosis. Biomark Insights. 2013;8:127–36. doi: 10.4137/bmi.s13154.PubMedPubMedCentralGoogle Scholar
  58. 58.
    Mozzoni P, Banda I, Goldoni M, Corradi M, Tiseo M, Acampa O, et al. Plasma and EBC microRNAs as early biomarkers of non-small-cell lung cancer. Biomarkers. 2013;18:679–86. doi: 10.3109/1354750x.2013.845610.CrossRefPubMedGoogle Scholar
  59. 59.
    Shen J, Liao J, Guarnera MA, Fang H, Cai L, Stass SA, et al. Analysis of microRNAs in sputum to improve computed tomography for lung cancer diagnosis. J Thorac Oncol. 2014;9:33–40. doi: 10.1097/jto.0000000000000025.CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Shen J, Todd NW, Zhang H, Yu L, Lingxiao X, Mei Y, et al. Plasma microRNAs as potential biomarkers for non-small-cell lung cancer. Lab Investig. 2011;91:579–87. doi: 10.1038/labinvest.2010.194.CrossRefPubMedGoogle Scholar
  61. 61.
    Tang D, Shen Y, Wang M, Yang R, Wang Z, Sui A, et al. Identification of plasma microRNAs as novel noninvasive biomarkers for early detection of lung cancer. Eur J Cancer Prev. 2013;22:540–8. doi: 10.1097/CEJ.0b013e32835f3be9.CrossRefPubMedGoogle Scholar
  62. 62.
    Wei J, Liu LK, Gao W, Zhu CJ, Liu YQ, Cheng T, et al. Reduction of plasma microRNA-21 is associated with chemotherapeutic response in patients with non-small cell lung cancer. Chin J Cancer Res. 2011;23:123–8. doi: 10.1007/s11670-011-0123-2.CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Xie Y, Todd NW, Liu Z, Zhan M, Fang H, Peng H, et al. Altered miRNA expression in sputum for diagnosis of non-small cell lung cancer. Lung Cancer. 2010;67:170–6. doi: 10.1016/j.lungcan.2009.04.004.CrossRefPubMedGoogle Scholar
  64. 64.
    Baraniskin A, Kuhnhenn J, Schlegel U, Chan A, Deckert M, Gold R, et al. Identification of microRNAs in the cerebrospinal fluid as marker for primary diffuse large B-cell lymphoma of the central nervous system. Blood. 2011;117:3140–6. doi: 10.1182/blood-2010-09-308684.CrossRefPubMedGoogle Scholar
  65. 65.
    Mao X, Sun Y, Tang J. Serum miR-21 is a diagnostic and prognostic marker of primary central nervous system lymphoma. Neurol Sci. 2014;35:233–8.CrossRefPubMedGoogle Scholar
  66. 66.
    Liu X, Luo HN, Tian WD, Lu J, Li G, Wang L, et al. Diagnostic and prognostic value of plasma microRNA deregulation in nasopharyngeal carcinoma. Cancer Biol Ther. 2013;14:1133–42. doi: 10.4161/cbt.26170.
  67. 67.
    Gombos K, Horvath R, Szele E, Juhasz K, Gocze K, Somlai K, et al. miRNA expression profiles of oral squamous cell carcinomas. Anticancer Res. 2013;33:1511–7.PubMedGoogle Scholar
  68. 68.
    Ouyang L, Liu P, Yang S, Ye S, Xu W, Liu X. A three-plasma miRNA signature serves as novel biomarkers for osteosarcoma. Med Oncol. 2013;30:340. doi: 10.1007/s12032-012-0340-7.CrossRefPubMedGoogle Scholar
  69. 69.
    Dillhoff M, Liu J, Frankel W, Croce C, Bloomston M. MicroRNA-21 is overexpressed in pancreatic cancer and a potential predictor of survival. J Gastrointest Surg. 2008;12:2171–6. doi: 10.1007/s11605-008-0584-x.CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    Habbe N, Koorstra JB, Mendell JT, Offerhaus GJ, Ryu JK, Feldmann G, et al. MicroRNA miR-155 is a biomarker of early pancreatic neoplasia. Cancer Biol Ther. 2009;8:340–6.CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Liu JQ, Gao J, Ren Y, Wang XW, Wang WW, Lu H. Diagnostic value of plasma miR-21 in pancreatic cancer. World Chin J Digestol. 2011;19:860–3.Google Scholar
  72. 72.
    Ryu JK, Matthaei H, Dal Molin M, Hong SM, Canto MI, Schulick RD, et al. Elevated microRNA miR-21 levels in pancreatic cyst fluid are predictive of mucinous precursor lesions of ductal adenocarcinoma. Pancreatology. 2011;11:343–50. doi: 10.1159/000329183.CrossRefPubMedPubMedCentralGoogle Scholar
  73. 73.
    Wang J, Chen J, Chang P, LeBlanc A, Li D, Abbruzzesse JL, et al. MicroRNAs in plasma of pancreatic ductal adenocarcinoma patients as novel blood-based biomarkers of disease. Cancer Prev Res (Phila). 2009;2:807–13. doi: 10.1158/1940-6207.capr-09-0094.CrossRefGoogle Scholar
  74. 74.
    Yaman Agaoglu F, Kovancilar M, Dizdar Y, Darendeliler E, Holdenrieder S, Dalay N, et al. Investigation of miR-21, miR-141, and miR-221 in blood circulation of patients with prostate cancer. Tumour Biol. 2011;32:583–8. doi: 10.1007/s13277-011-0154-9.CrossRefPubMedGoogle Scholar
  75. 75.
    Faragalla H, Youssef YM, Scorilas A, Khalil B, White NM, Mejia-Guerrero S, et al. The clinical utility of miR-21 as a diagnostic and prognostic marker for renal cell carcinoma. J Mol Diagn. 2012;14:385–92. doi: 10.1016/j.jmoldx.2012.02.003.CrossRefPubMedGoogle Scholar
  76. 76.
    Silva-Santos RM, Costa-Pinheiro P, Luis A, Antunes L, Lobo F, Oliveira J, et al. MicroRNA profile: a promising ancillary tool for accurate renal cell tumour diagnosis. Br J Cancer. 2013;109:2646–53. doi: 10.1038/bjc.2013.552.CrossRefPubMedPubMedCentralGoogle Scholar
  77. 77.
    Meng X, Liu Y, Liu B. Glutathione S-transferase M1 null genotype meta-analysis on gastric cancer risk. Diagn Pathol. 2014;9:122. doi: 10.1186/1746-1596-9-122.CrossRefPubMedPubMedCentralGoogle Scholar
  78. 78.
    Keutgen XM, Filicori F, Crowley MJ, Wang Y, Scognamiglio T, Hoda R, et al. A panel of four miRNAs accurately differentiates malignant from benign indeterminate thyroid lesions on fine needle aspiration. Clin Cancer Res. 2012;18:2032–8. doi: 10.1158/1078-0432.ccr-11-2487.CrossRefPubMedGoogle Scholar
  79. 79.
    Mazeh H, Levy Y, Mizrahi I, Appelbaum L, Ilyayev N, Halle D, et al. Differentiating benign from malignant thyroid nodules using micro ribonucleic acid amplification in residual cells obtained by fine needle aspiration biopsy. J Surg Res. 2013;180:216–21. doi: 10.1016/j.jss.2012.04.051.CrossRefPubMedGoogle Scholar
  80. 80.
    Lee H, Choi HJ, Kang CS, Lee HJ, Lee WS, Park CS. Expression of miRNAs and PTEN in endometrial specimens ranging from histologically normal to hyperplasia and endometrial adenocarcinoma. Mod Pathol. 2012;25:1508–15. doi: 10.1038/modpathol.2012.111.CrossRefPubMedGoogle Scholar
  81. 81.
    Tsukamoto O, Miura K, Mishima H, Abe S, Kaneuchi M, Higashijima A et al. Identification of endometrioid endometrial carcinoma-associated microRNAs in tissue and plasma. Gynecol Oncol. 2014;132:715–21. doi: 10.1016/j.ygyno.2014.01.029.
  82. 82.
    Kumarswamy R, Volkmann I, Thum T. Regulation and function of miRNA-21 in health and disease. RNA Biol. 2011;8:706–13. doi: 10.4161/rna.8.5.16154.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Lijun Shen
    • 1
    • 2
  • Zhihong Wan
    • 3
  • Yuming Ma
    • 3
  • Libing Wu
    • 2
  • Fangfang Liu
    • 3
  • Hong Zang
    • 3
  • Shaojie Xin
    • 1
    • 3
  1. 1.Medical School of Chinese PLABeijingChina
  2. 2.Department of the Liver Cirrhosis Diagnosis and Treatment Center302 Military Hospital of ChinaBeijingChina
  3. 3.Liver Failure Treatment and Research Center302 Military Hospital of ChinaBeijingChina

Personalised recommendations