Skip to main content

Advertisement

SpringerLink
Log in

The expression and clinical significance of circulating microRNA-21 in serum of five solid tumors

  • Original Paper
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Purpose

MicroRNA-21 (miR-21) was reported as being overexpressed in various human cancerous tissues, but its expression in cancerous serum was not unanimous in different laboratories. On the base of optimizing experimental design and improving trial protocol, we wanted to know whether the circulating microRNA-21 was dysregulated in the common solid cancers.

Methods

Using SYBR green real-time quantitative reverse transcription-PCR, we detected the expression of circulating miR-21 in 174 patients with solid cancers and 39 normal control subjects, including breast cancer, esophageal cancer, gastric cancer, colorectal cancer, lung cancer. Furthermore, we analyzed the associations between miR-21 expression and clinical features of patients.

Results

miR-21 was significantly overexpressed in human solid cancerous serum relative to normal control (P < 0.001), and its sensitivity and specificity were significantly higher than the currently used tumor markers. High miR-21 expression was not correlated with gender, age, clinical stage, and lymph node metastasis status.

Conclusion

Circulating miR-21 could serve as a potential broad-spectrum serum-based biomarker for the detection of some solid cancers.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Abbreviations

miR-21:

MicroRNA-21

Ct:

Cycle threshold

ROC:

Receiver operating characteristic

RT-NTC:

Reverse transcription negative controls

TPM1:

Tumor suppressor genes tropomyosin 1

PDCD4:

Programmed cell death 4

PTEN:

Phosphatase and tensin homolog

RECK:

Reversion-inducing cysteine-rich protein with Kazal motifs

BC:

Breast cancer

CRC:

Colorectal cancer

LC:

Lung cancer

EC:

Esophageal cancer

GC:

Gastric cancer

References

  • Asaga S, Kuo C, Nguyen T, Terpenning M, Giuliaono AE, Hoon DSB (2011) Direct serum assay for microRNA-21 concentrations in early and advanced breast cancer. Clin Chem 57(1):84–91

    Article  PubMed  CAS  Google Scholar 

  • Asangani A, Rasheed SAK, Nikolova DA, Leupold JH, Colburn NH, Post S, Allgayer H (2008) MicroRNA-21 (miR-21) post-transcriptionally downregulates tumor suppressor Pdcd4 and stimulates invasion, intravasation and metastasis in colorectal cancer. Oncogene 27:2128–2136

    Article  PubMed  CAS  Google Scholar 

  • Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116(2):281–297

    Article  PubMed  CAS  Google Scholar 

  • Brase JC, Wuttig D, Kuner R, Sültmann H (2010) Serum microRNAs as non-invasive biomarkers for cancer. Mol Cancer 9:306

    Article  PubMed  CAS  Google Scholar 

  • Brown BD, Naldini L (2009) Exploiting and antagonizing microRNA regulation for therapeutic and experimental applications. Nat Rev Genet 10:578–585

    Article  PubMed  CAS  Google Scholar 

  • Calin GA, Sevignani C, Dumitru CD, Hyslop T, Noch E, Yendamuri S, Shimizu M, Rattan S, Bullrich F, Negrini M, Croce CM (2004) Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci USA 101(9):2999–3004

    Article  PubMed  CAS  Google Scholar 

  • Chen X, Ba Y, Ma LJ, Cai X, Yin Y, Wang KH, Guo JG, Zhang YJ, Chen JN, Guo X, Li QB, Li XY, Wang WJ, Zhang Y, Wang J, Jiang XY, Xiang Y, Xu C, Zheng PP, Zhang JB, Li RQ, Zhang HJ, Shang XB, Gong T, Ning G, Wang J, Zen K, Zhang JF, Zhang CY (2008) Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res 18(10):997–1006

    Article  PubMed  CAS  Google Scholar 

  • Duffy MJ (2001) Clinical uses of tumor markers: a critical review. Crit Rev Clin Lab Sci 38(3):225–262

    Article  PubMed  CAS  Google Scholar 

  • Duffy MJ (2007) Role of tumor markers in patients with solid cancers: a critical review. Eur J Intern Med 18(3):175–184

    Article  PubMed  CAS  Google Scholar 

  • Edge SB, Compton CC (2010) The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol 17(6):1471–1474

    Article  PubMed  Google Scholar 

  • Esquela-Kerscher A, Slack FJ (2006) Oncomirs—microRNAs with a role in cancer. Nat Rev Cancer 6(4):259–269

    Article  PubMed  CAS  Google Scholar 

  • Griffiths-Jones S, Grocock RJ, van Dongen S, Bateman A, Enright AJ (2006) MiRBase: microRNA sequences, targets and gene nomenclature. Nucleic Acids Res 34:D140–D144

    Article  PubMed  CAS  Google Scholar 

  • Heneghan HM, Miller N, Lowery AJ, Sweeney KJ, Newell J, Kerin MJ (2010) Circulating microRNAs as novel minimally invasive biomarkers for breast cancer. Ann Surg 251(3):499–505

    Article  PubMed  Google Scholar 

  • Hu ZB, Chen X, Zhao Y, Tian T, Jin GF, Shu YQ, Chen YJ, Xu L, Zen K, Zhang CY, Shen HB (2010) Serum microRNA signatures identified in a genome-wide serum microRNA expression profiling predict survival of non-small-cell lung cancer. J Clin Oncol 28(10):1721–1726

    Article  PubMed  Google Scholar 

  • Huang ZH, Huang D, Ni SJ, Peng ZL, Sheng WQ, Du X (2010) Plasma microRNAs are promising novel biomarkers for early detection of colorectal cancer. Int J Cancer 127(1):118–126

    Article  PubMed  CAS  Google Scholar 

  • Jemal A, Freddie B, Melissa MC, Jacques F, Elizabeth W, David F (2011) Global cancer statistics. CA Cancer J Clin 61(2):69–90

    Article  PubMed  Google Scholar 

  • Kosaka N, Iguchi H, Ochiya T (2010) Circulating microRNA in body fluid: a new potential biomarker for cancer diagnosis and prognosis. Cancer Sci 101(10):2087–2092

    Article  PubMed  CAS  Google Scholar 

  • Lawrie CH, Gal S, Dunlop HM, Pushkaran B, Liggins AP, Pulford K, Banham AH, Pezzella F, Boultwood J, Wainscoat JS, Hatton CSR, Harris AL (2008) Detection of elevated levels of tumour-associated microRNAs in serum of patients with diffuse large B-cell lymphoma. Br J Haematol 141(5):672–675

    Article  PubMed  Google Scholar 

  • Lewis BP, Burge CB, Bartel DP (2005) Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 120(1):15–20

    Article  PubMed  CAS  Google Scholar 

  • Liu CJ, Kao SY, Tu HF, Tsai MM, Chang KW, Lin SC (2010) Increase of microRNA miR-31 level in plasma could be a potential marker of oral cancer. Oral Dis 16(4):360–364

    Article  PubMed  Google Scholar 

  • Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 25(4):402–408

    Article  PubMed  CAS  Google Scholar 

  • Love TM, Moffett HF, Novina CD (2008) Not miR-ly small RNAs: big potential for microRNAs in therapy. J Allergy Clin Immunol 121(2):309–319

    Article  PubMed  CAS  Google Scholar 

  • Meng FY, Henson R, Wehbe-Janek H, Ghoshal K, Jacob ST, Patel T (2007) MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer. Gastroenterology 133(2):647–658

    Article  PubMed  CAS  Google Scholar 

  • Roulston JE (1990) Limitations of tumour markers in screening. Br J Surg 77(9):961–962

    Article  PubMed  CAS  Google Scholar 

  • Schmittgen TD, Jiang JM, Liu Q, Yang LQ (2004) A high-throughput method to monitor the expression of microRNA precursors. Nucleic Acids Res 32(4):e43

    Article  PubMed  Google Scholar 

  • Shen J, Todd NW, Zhang H, Yu L, Lingxiao X, Mei YP, Guarnera M, Liao JP, Chou A, Lu CL, Jiang ZR, Fang HB, Katz RL, Jiang F (2011) Plasma microRNAs as potential biomarkers for non-small-cell lung cancer. Lab Invest 91(4):579–587

    Article  PubMed  CAS  Google Scholar 

  • Song JN, Bai ZG, Han W, Zhang J, Meng H, Bi JT, Ma XM, Han SW, Zhang ZT (2011) Identification of suitable reference genes for qPCR analysis of serum microRNA in gastric cancer patients. Dig Dis Sci 57(4):897–904

    Article  PubMed  Google Scholar 

  • Thomas CMG, Sweep CGJ (2001) Serum tumor markers: past, state of the art, and future. Int J Biol Markers 16(2):73–86

    PubMed  CAS  Google Scholar 

  • Wang J, Chen J, Chang P, LeBlanc A, Li DH, Abbruzzesse JL, Frazier ML, Killary AM, Sen S (2009) MicroRNAs in plasma of pancreatic ductal adenocarcinoma patients as novel blood-based biomarkers of disease. Cancer Prev Res (Phila Pa) 2(9):807–813

    Article  CAS  Google Scholar 

  • Wang F, Zheng Z, Guo J, Ding X (2010) Correlation and quantitation of micrRNA aberrant expression in tissue and sera from patients with breast tumor. Gynecol Oncol 119(3):586–593

    Article  PubMed  CAS  Google Scholar 

  • Wong TS, Liu XB, Wong BYH, Ng RWM, Yuen APW, Wei WL (2008) Mature miR-184 as potential oncogenic microRNA of squamous cell carcinoma of tongue. Clin Cancer Rse 14(9):2588–2592

    Article  CAS  Google Scholar 

  • Xiao JJ, Jing ZC, Ellinor PT, Liang DD, Zhang H, Liu Y, Chen XL, Pan L, Lyon R, Liu Y, Peng LY, Liang XQ, Sun YF, Popescu LM, Condorelli G, Chen YH (2011) MicroRNA-134 as a potential plasma biomarker for the diagnosis of acute pulmonary embolism. J Transl Med 9:159

    Article  PubMed  CAS  Google Scholar 

  • Yan LX, Huang XF, Shao Q, Huang MY, Deng L, Wu QL, Zeng YX, Shao JY (2008) MicroRNA miR-21 overexpression in human breast cancer is associated with advanced clinical stage, lymph node metastasis and patient poor prognosis. RNA 14(11):2348–2360

    Article  PubMed  CAS  Google Scholar 

  • Zamore PD, Haley B (2005) Ribo-gnome: the big world of small RNAs. Science 309(5740):1519–1524

    Article  PubMed  CAS  Google Scholar 

  • Zhang ZY, Li ZJ, Gao CP, Chen P, Chen JJ, Liu WZ, Xiao SD, Lu H (2008) miR-21 plays a pivotal role in gastric cancer pathogenesis and progression. Lab Invest 88(12):1358–1366

    Article  PubMed  CAS  Google Scholar 

  • Zheng DL, Haddadin S, Wang Y, Gu LQ, Perry MC, Freter CE, Wang MX (2011) Plasma microRNAs as novel biomarkers for early detection of lung cancer. Int J Clin Exp Pathol 4(6):575–586

    PubMed  CAS  Google Scholar 

  • Zhu SM, Si M-L, Wu H, Mo YY (2007) MicroRNA-21 targets the tumor suppressor gene tropomyosin 1 (TPM1). J Biol Chem 282(19):14328–14336

    Article  PubMed  CAS  Google Scholar 

  • Zhu SM, Wu HL, Wu FT, Nie DT, Sheng SJ, Mo YY (2008) MicroRNA-21 targets tumor suppressor genes in invasion and metastasis. Cell Res 18(3):350–359

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We thank all subjects who participated in this study.

Conflict of interest

The authors declare that neither financial nor non-financial competing interests exist.

Author information

Authors and Affiliations

  1. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Clinical Laboratory, Peking University Cancer Hospital and Institute, 52 Fucheng Road, Haidian District, Beijing, 100142, People’s Republic of China

    Bing Wang & Qingyun Zhang

Authors
  1. Bing Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Qingyun Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Qingyun Zhang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wang, B., Zhang, Q. The expression and clinical significance of circulating microRNA-21 in serum of five solid tumors. J Cancer Res Clin Oncol 138, 1659–1666 (2012). https://doi.org/10.1007/s00432-012-1244-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00432-012-1244-9

Keywords

Search

Navigation