Tumor Biology

, Volume 36, Issue 5, pp 3541–3547 | Cite as

MD-miniRNA could be a more accurate biomarker for prostate cancer screening compared with serum prostate-specific antigen level

  • Dong Xue
  • Cui-Xing Zhou
  • Yun-Bo Shi
  • Hao Lu
  • Xiao-Zhou He
Research Article


Prostate cancer and prostatic hyperplasia detection remains a great challenge, lacking of effective non-invasive and specific diagnostic biomarkers. In the current study, we aimed to identify the relative expression of plasma MD-miniRNA and its diagnostic performance in differentiating prostate cancer and prostatic hyperplasia patients from healthy controls, compared with serum prostate-specific antigen (PSA) level. All of the clinical participants (63 prostate cancer patients, 32 prostatic hyperplasia patients, and 50 healthy controls) were obtained from the Third Affiliated Hospital of Suzhou University in China between January 2013 and April 2014. Clinical characteristics were well matched. Plasma samples were extracted to test the relative expression of MD-miniRNA using the method of qRT-PCR. SPSS 22.0 statistical software package was used to analyze the data and GraphPad Prism 6.0 was used to generate the graphs. Relativity expression of plasma MD-miniRNA was significantly upregulated in prostate cancer, compared with prostatic hyperplasia patients and healthy controls. Serum PSA level revealed similar differences among these groups. MD-miniRNA presented a relatively high diagnostic accuracy with AUC of 0.86 (95 % CI 0.80–0.93) in differentiating prostate cancer patients from healthy controls. Simultaneously, MD-miniRNA was able to discriminate prostate cancer patients from prostatic hyperplasia controls with AUC of 0.79 (95 % CI 0.70–0.88). In addition, MD-miniRNA displayed a better diagnostic performance than PSA level. However, the panel of these two biomarkers revealed the best diagnostic performance, compared with either single biomarker. Results of this study showed that plasma MD-miniRNA could serve as a promising and noninvasive biomarker for diagnosing prostate cancer. Further large-scale studies are needed to confirm its clinical diagnosis accuracy.


Plasma MD-miniRNA Diagnosis Prostate cancer Prostatic hyperplasia 


Conflicts of interest



This study was funded by the Supporting Program of Changzhou Science and Technology Bureau (CE20135046) and 2013 Jiangsu Province Health Department Medical Research Bid Project (H201348).


  1. 1.
    Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin. 2014;64:9–29.CrossRefPubMedGoogle Scholar
  2. 2.
    Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.CrossRefPubMedGoogle Scholar
  3. 3.
    Peyromaure EM, Mao K, Sun Y, Xia S, Jiang N, Zhang S, et al. A comparative study of prostate cancer detection and management in China and in France. Can J Urol. 2009;16:4472–7.PubMedGoogle Scholar
  4. 4.
    Zeigler-Johnson CM, Rennert H, Mittal RD, Jalloh M, Sachdeva R, Malkowicz SB, et al. Evaluation of prostate cancer characteristics in four populations worldwide. Can J Urol. 2008;15:4056–64.PubMedPubMedCentralGoogle Scholar
  5. 5.
    Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin. 2010;60:277–300.CrossRefPubMedGoogle Scholar
  6. 6.
    Sboner A, Demichelis F, Calza S, Pawitan Y, Setlur SR, Hoshida Y, et al. Molecular sampling of prostate cancer: a dilemma for predicting disease progression. BMC Med Genomics. 2010;3:8.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Berthold DR, Sternberg CN, Tannock IF. Management of advanced prostate cancer after first-line chemotherapy. J Clin Oncol Off J Am Soc Clin Oncol. 2005;23:8247–52.CrossRefGoogle Scholar
  8. 8.
    Mazhar D, Waxman J. Early chemotherapy in prostate cancer. Nat Clin Pract Urol. 2008;5:486–93.CrossRefPubMedGoogle Scholar
  9. 9.
    Wilkinson S, Chodak GW. Critical review of complementary therapies for prostate cancer. J Clin Oncol Off J Am Soc Clin Oncol. 2003;21:2199–210.CrossRefGoogle Scholar
  10. 10.
    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.CrossRefPubMedGoogle Scholar
  11. 11.
    Zhang C, Wang C, Chen X, Yang C, Li K, Wang J, et al. Expression profile of micrornas in serum: a fingerprint for esophageal squamous cell carcinoma. Clin Chem. 2010;56:1871–9.CrossRefPubMedGoogle Scholar
  12. 12.
    Yang C, Wang C, Chen X, Chen S, Zhang Y, Zhi F, et al. 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. 2013;132:116–27.CrossRefGoogle Scholar
  13. 13.
    Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL, et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci U S A. 2008;105:10513–8.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Srivastava A, Goldberger H, Dimtchev A, Marian C, Soldin O, Li X, et al. Circulatory mir-628-5p is downregulated in prostate cancer patients. Tumour Biol J Int Soc Oncodev Biol Med. 2014;35:4867–73.CrossRefGoogle Scholar
  15. 15.
    Brosnan CA, Voinnet O. The long and the short of noncoding RNAs. Curr Opin Cell Biol. 2009;21:416–25.CrossRefPubMedGoogle Scholar
  16. 16.
    Zaratiegui M, Irvine DV, Martienssen RA. Noncoding RNAs and gene silencing. Cell. 2007;128:763–76.CrossRefPubMedGoogle Scholar
  17. 17.
    Ender C, Krek A, Friedlander MR, Beitzinger M, Weinmann L, Chen W, et al. A human snoRNA with microRNA-like functions. Mol Cell. 2008;32:519–28.CrossRefPubMedGoogle Scholar
  18. 18.
    Mattick JS. The functional genomics of noncoding RNA. Science. 2005;309:1527–8.CrossRefPubMedGoogle Scholar
  19. 19.
    Carninci P, Kasukawa T, Katayama S, Gough J, Frith MC, Maeda N, et al. The transcriptional landscape of the mammalian genome. Science. 2005;309:1559–63.CrossRefPubMedGoogle Scholar
  20. 20.
    Motamedi MR, Verdel A, Colmenares SU, Gerber SA, Gygi SP, Moazed D. Two RNAi complexes, rits and rdrc, physically interact and localize to noncoding centromeric RNAs. Cell. 2004;119:789–802.CrossRefPubMedGoogle Scholar
  21. 21.
    Ramskold D, Wang ET, Burge CB, Sandberg R. An abundance of ubiquitously expressed genes revealed by tissue transcriptome sequence data. PLoS Comput Biol. 2009;5:e1000598.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Costa FF. Non-coding rnas: Meet thy masters. Bioessays News Rev Mol Cell Dev Biol. 2010;32:599–608.CrossRefGoogle Scholar
  23. 23.
    Wright CM, Kirschner MB, Cheng YY, O’Byrne KJ, Gray SG, Schelch K, et al. Long noncoding RNAs (lncRNAs) are dysregulated in malignant pleural mesothelioma (mpm). PLoS One. 2013;8:e70940.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Li H, Yu B, Li J, Su L, Yan M, Zhu Z, et al. Overexpression of lncRNA h19 enhances carcinogenesis and metastasis of gastric cancer. Oncotarget. 2014;5:2318–29.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Fu X, Ravindranath L, Tran N, Petrovics G, Srivastava S. Regulation of apoptosis by a prostate-specific and prostate cancer-associated noncoding gene, pcgem1. DNA Cell Biol. 2006;25:135–41.CrossRefPubMedGoogle Scholar
  26. 26.
    Geng YJ, Xie SL, Li Q, Ma J, Wang GY. Large intervening non-coding RNA HOTAIR is associated with hepatocellular carcinoma progression. J Int Med Res. 2011;39:2119-2128.Google Scholar
  27. 27.
    Wang XS, Zhang Z, Wang HC, Cai JL, Xu QW, Li MQ, et al. Rapid identification of uca1 as a very sensitive and specific unique marker for human bladder carcinoma. Clin Cancer Res an Off J Am Assoc Cancer Res. 2006;12:4851–8.CrossRefGoogle Scholar
  28. 28.
    Gutschner T, Hammerle M, Eissmann M, Hsu J, Kim Y, Hung G, et al. The noncoding RNA malat1 is a critical regulator of the metastasis phenotype of lung cancer cells. Cancer Res. 2013;73:1180–9.CrossRefPubMedGoogle Scholar
  29. 29.
    Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin. 2012;62:10–29.CrossRefPubMedGoogle Scholar
  30. 30.
    Oelke M, Bachmann A, Descazeaud A, Emberton M, Gravas S, Michel MC, et al. Eau guidelines on the treatment and follow-up of non-neurogenic male lower urinary tract symptoms including benign prostatic obstruction. Eur Urol. 2013;64:118–40.CrossRefPubMedGoogle Scholar
  31. 31.
    The management of lower urinary tract symptoms in men. London, 2010Google Scholar
  32. 32.
    Prensner JR, Chen W, Iyer MK, Cao Q, Ma T, Han S, et al. Pcat-1, a long noncoding RNA, regulates brca2 and controls homologous recombination in cancer. Cancer Res. 2014;74:1651–60.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Gandini O, Santulli M, Cardillo MR, Stigliano A, Toscano V: Correspondence re: J. B. De kok et al., dd3, a very sensitive and specific marker to detect prostate tumors. Cancer res., 62: 2695–2698, 2002. Cancer research 2003;63:4747; author reply 4748–4749Google Scholar
  34. 34.
    De Marzo AM, Coffey DS, Nelson WG. New concepts in tissue specificity for prostate cancer and benign prostatic hyperplasia. Urology. 1999;53:29–39. discussion 39–42.CrossRefPubMedGoogle Scholar
  35. 35.
    Gupta RA, Shah N, Wang KC, Kim J, Horlings HM, Wong DJ, et al. Long non-coding rna hotair reprograms chromatin state to promote cancer metastasis. Nature. 2010;464:1071–6.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Rinn JL, Kertesz M, Wang JK, Squazzo SL, Xu X, Brugmann SA, et al. Functional demarcation of active and silent chromatin domains in human hox loci by noncoding RNAs. Cell. 2007;129:1311–23.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Prensner JR, Iyer MK, Balbin OA, Dhanasekaran SM, Cao Q, Brenner JC, et al. Transcriptome sequencing across a prostate cancer cohort identifies pcat-1, an unannotated lincrna implicated in disease progression. Nat Biotechnol. 2011;29:742–9.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Huarte M, Rinn JL. Large non-coding RNAs: missing links in cancer? Hum Mol Genet. 2010;19:R152–61.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Poliseno L, Salmena L, Zhang J, Carver B, Haveman WJ, Pandolfi PP. A coding-independent function of gene and pseudogene mRNAs regulates tumour biology. Nature. 2010;465:1033–8.CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Ren S, Wang F, Shen J, Sun Y, Xu W, Lu J, et al. Long non-coding rna metastasis associated in lung adenocarcinoma transcript 1 derived minirna as a novel plasma-based biomarker for diagnosing prostate cancer. Eur J Cancer. 2013;49:2949–59.CrossRefPubMedGoogle Scholar
  41. 41.
    Bond CS, Fox AH. Paraspeckles: nuclear bodies built on long noncoding RNA. J Cell Biol. 2009;186:637–44.CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Matouk IJ, Mezan S, Mizrahi A, Ohana P, Abu-Lail R, Fellig Y, et al. The oncofetal h19 rna connection: hypoxia, p53 and cancer. Biochim Biophys Acta. 1803;2010:443–51.Google Scholar
  43. 43.
    Barsyte-Lovejoy D, Lau SK, Boutros PC, Khosravi F, Jurisica I, Andrulis IL, et al. The c-myc oncogene directly induces the h19 noncoding RNA by allele-specific binding to potentiate tumorigenesis. Cancer Res. 2006;66:5330–7.CrossRefPubMedGoogle Scholar
  44. 44.
    Berteaux N, Lottin S, Monte D, Pinte S, Quatannens B, Coll J, et al. H19 mRNA-like noncoding RNA promotes breast cancer cell proliferation through positive control by e2f1. J Biol Chem. 2005;280:29625–36.CrossRefPubMedGoogle Scholar
  45. 45.
    Fellig Y, Ariel I, Ohana P, Schachter P, Sinelnikov I, Birman T, et al. H19 expression in hepatic metastases from a range of human carcinomas. J Clin Pathol. 2005;58:1064–8.CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Weiss M, Plass C, Gerhauser C. Role of lncRNAs in prostate cancer development and progression. Biol Chem. 2014;395:1275–90.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Dong Xue
    • 1
  • Cui-Xing Zhou
    • 1
  • Yun-Bo Shi
    • 2
  • Hao Lu
    • 1
  • Xiao-Zhou He
    • 1
  1. 1.Department of Urology, Third Affiliated HospitalSuzhou UniversityChangzhouChina
  2. 2.Foreign Languages SchoolChangzhou Institute of TechnologyChangzhouChina

Personalised recommendations