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MicroRNAs used as novel biomarkers for detecting cancer metastasis

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Tumor Biology

Abstract

The low survival rates of cancers are primarily due to late diagnosis and metastasis. Discriminating the metastasis is a crucial factor for prognosis and improving the survival rate of cancer patients. MicroRNAs (miRNAs) can regulate the expression of hundreds of downstream genes, which has a broad effect on the regulation of the whole cell cycle. Accumulating studies have found that the aberrant expression of miRNAs is associated with cancer genesis. The aim of this study is to evaluate the diagnostic value of miRNAs in detecting cancer metastasis. Medline, PubMed, Embase, and CNKI were searched for relevant articles. Sensitivity, specificity, positive and negative likelihood ratio (PLR, NLR) and diagnostic odds ratio (DOR), the summary receiver operator characteristic (SROC) curve and the calculated AUC (area under the SROC curve) were applied to explore the diagnostic accuracy of miRNAs in metastasis. Seven hundred seventy-one metastatic cancer patients and 552 non-metastatic cancer controls from 14 articles were involved in our meta-analysis. A sensitivity of 0.75 (95 % confidence interval (CI), 0.72–0.79) and a specificity of 0.80 (95 % CI, 0.76–0.84) were observed from metastatic patients and non-metastatic controls in the combined analysis. And the AUC was 0.83 (95 % CI, 0.79–0.86). In addition, results from subgroup analyses suggested that a higher diagnostic value for metastasis was acquired in tissue sample other than blood sample (sensitivity, 0.82 versus 0.73; specificity, 0.84 versus 0.79; PLR, 5.0 versus 3.5; NLR, 0.22 versus 0.34; DOR, 23 versus 10; AUC, 0.88 versus 0.80). In summary, this meta-analysis proved the relatively high diagnostic value of miRNA in metastasis, which might be applied as a novel screening tool to detect metastasis along with other biomarkers. We also illustrated that tissue-based miRNAs may have a better diagnostic accuracy than blood-based miRNAs.

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References

  1. DeSantis CE, Lin CC, Mariotto AB, Siegel RL, Stein KD, Kramer JL, et al. Cancer treatment and survivorship statistics, 2014. CA Cancer J Clin. 2014;64:252–71.

    Article  PubMed  Google Scholar 

  2. 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.

    Article  CAS  PubMed  Google Scholar 

  3. El-Serag HB, Rudolph KL. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology. 2007;132:2557–76.

    Article  CAS  PubMed  Google Scholar 

  4. 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;7:14.

    Google Scholar 

  5. Sturgeon CM, Duffy MJ, Hofmann BR, Lamerz R, Fritsche HA, Gaarenstroom K, et al. National academy of clinical biochemistry laboratory medicine practice guidelines for use of tumor markers in liver, bladder, cervical, and gastric cancers. Clin Chem. 2010;56:5.

    Article  Google Scholar 

  6. Metindir J, Bilir DG. Evaluation of prognostic significance in extracapsular spread of pelvic lymph node metastasis in patients with cervical cancer. Eur J Gynaecol Oncol. 2008;29:476–8.

    CAS  PubMed  Google Scholar 

  7. Biewenga P, van der Velden J, Mol BW, Stalpers LJ, Schilthuis MS, van der Steeg JW, et al. Prognostic model for survival in patients with early stage cervical cancer. Cancer. 2011;117:768–76.

    Article  PubMed  Google Scholar 

  8. Lowery AJ, Walsh S, McDermott EW, Prichard RS. Molecular and therapeutic advances in the diagnosis and management of malignant pheochromocytomas and paragangliomas. Oncologist. 2013;18:391–407.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Chen J, Yao D, Li Y, Chen H, He C, Ding N, et al. Serum microRNA expression levels can predict lymph node metastasis in patients with early-stage cervical squamous cell carcinoma. Int J Mol Med. 2013;32:557–67. doi:10.3892/ijmm.2013.1424.

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Chen JY, Yao DS, He CJ, Lu Y. [Relationship between serum miR-21 and lymph node metastasis in cervical cancer]. J Xi’an Jiaotong Univ (Med Sci). 2012;33:351–5.

    Google Scholar 

  11. Chen Q, Ge X, Zhang Y, Xia H, Yuan D, Tang Q, et al. Plasma miR-122 and miR-192 as potential novel biomarkers for the early detection of distant metastasis of gastric cancer. Oncol Rep. 2014;31:1863–70. doi:10.3892/or.2014.3004.

    CAS  PubMed  Google Scholar 

  12. Chen W, Cai F, Zhang B, Barekati Z, Zhong XY. The level of circulating miRNA-10b and miRNA-373 in detecting lymph node metastasis of breast cancer: potential biomarkers. Tumour Biol. 2013;34:455–62. doi:10.1007/s13277-012-0570-5.

    Article  CAS  PubMed  Google Scholar 

  13. Chen YX, Ma CL, Chen ZF, Zhang W. Clinical significance of miR-143 expression in women with cervical cancer of Uyghur and Han ethnicities, in Xinjiang. Zhonghua Liu Xing Bing Xue Za Zhi. 2013;34:1120–4.

    CAS  PubMed  Google Scholar 

  14. Feng L, Pang Z, Sha S, Wu B, Xu F, Yin SP. The value of diagnosis and prognosis prediction of serum mi-29a for colorectal cancer. Chin J Clin Oncol Rehabil. 2013;20:1313–5.

    Google Scholar 

  15. Huang L, Lin JX, Yu YH, Zhang MY, Wang HY, Zheng M. Downregulation of six microRNAs is associated with advanced stage, lymph node metastasis and poor prognosis in small cell carcinoma of the cervix. PLoS One. 2012;7:e33762. doi:10.1371/journal.pone.0033762.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Kim SY, Jeon TY, Choi CI, Kim DH, Kim GH, Ryu DY, et al. Validation of circulating miRNA biomarkers for predicting lymph node metastasis in gastric cancer. J Mol Diagn. 2013;15:661–9. doi:10.1016/j.jmoldx.2013.04.004.

    Article  PubMed  Google Scholar 

  17. Lu J, Xu X, Liu X, Peng Y, Zhang B, Wang L, et al. Predictive value of miR-9 as a potential biomarker for nasopharyngeal carcinoma metastasis. Br J Cancer. 2014;110:392–8. doi:10.1038/bjc.2013.751.

    Article  CAS  PubMed  Google Scholar 

  18. Wang LG, Gu J. Serum microRNA-29a is a promising novel marker for early detection of colorectal liver metastasis. Cancer Epidemiol. 2012;36:e61–7. doi:10.1016/j.canep.2011.05.002.

    Article  CAS  PubMed  Google Scholar 

  19. Wu WY, Xue XY, Chen ZJ, Han SL, Huang YP, Zhang LF, et al. Potentially predictive microRNAs of gastric cancer with metastasis to lymph node. World J Gastroenterol. 2011;17:3645–51. doi:10.3748/wjg.v17.i31.3645.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Yin J, Bai Z, Song J, Yang Y, Wang J, Han W, et al. Differential expression of serum miR-126, miR-141 and miR-21 as novel biomarkers for early detection of liver metastasis in colorectal cancer. Chin J Cancer Res. 2014;26:95–103. doi:10.3978/j.issn. 1000-9604.2014.02.07.

    PubMed  PubMed Central  Google Scholar 

  21. Zhao FL, Hu GD, Wang XF, Zhang XH, Zhang YK, Yu ZS. Serum overexpression of microRNA-10b in patients with bone metastatic primary breast cancer. J Int Med Res. 2012;40:859–66.

    Article  CAS  PubMed  Google Scholar 

  22. Zhao S, Yao D, Chen J, Ding N. Circulating miRNA-20a and miRNA-203 for screening lymph node metastasis in early stage cervical cancer. Genet Test Mol Biomark. 2013;17:631–6. doi:10.1089/gtmb.2013.0085.

    Article  CAS  Google Scholar 

  23. Leber MF, Efferth T. Molecular principles of cancer invasion and metastasis (review). Int J Oncol. 2009;34:881–95.

    CAS  PubMed  Google Scholar 

  24. Xu X, Yang X, Ru G, Wu Y, Zhang S, Xing C, et al. miR-146a gene polymorphism rs2910164 and the risk of digestive tumors: a meta-analysis of 21 case-control studies. Oncol Rep. 2014;31:472–9. doi:10.3892/or.2013.2854.

    CAS  PubMed  Google Scholar 

  25. Wan D, Gu W, Xu G, Shen C, Ding D, Shen S, et al. Effects of common polymorphisms rs2910164 in miR-146a and rs11614913 in miR-196a2 on susceptibility to colorectal cancer: a systematic review meta-analysis. Clin Transl Oncol. 2014. doi:10.1007/s12094-013-1150-x.

    Google Scholar 

  26. Li YJ, Zhang ZY, Mao YY, Jin MJ, Jing FY, Ye ZH, et al. A genetic variant in MiR-146a modifies digestive system cancer risk: a meta-analysis. Asian Pac J Cancer Prev. 2014;15:145–50.

    Article  PubMed  Google Scholar 

  27. Hua HB, Yan TT, Sun QM. miRNA polymorphisms and risk of gastric cancer in Asian population. World J Gastroenterol. 2014;20:5700–7. doi:10.3748/wjg.v20.i19.5700.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Hu Y, Yu CY, Wang JL, Guan J, Chen HY, Fang JY. MicroRNA sequence polymorphisms and the risk of different types of cancer. Sci Rep. 2014;4:3648. doi:10.1038/srep03648.

    PubMed  PubMed Central  Google Scholar 

  29. Takeshita F, Patrawala L, Osaki M, Takahashi RU, Yamamoto Y, Kosaka N, et al. Systemic delivery of synthetic microRNA-16 inhibits the growth of metastatic prostate tumors via downregulation of multiple cell-cycle genes. Mol Ther. 2010;18:181–7.

    Article  CAS  PubMed  Google Scholar 

  30. Rahim F, Hajizamani S, Mortaz E, Ahmadzadeh A, Shahjahani M, Shahrabi S, et al. Molecular regulation of bone marrow metastasis in prostate and breast cancer. Bone Marrow Res. 2014;405920:23.

    Google Scholar 

  31. Tavazoie SF, Alarcon C, Oskarsson T, Padua D, Wang Q, Bos PD, et al. Endogenous human microRNAs that suppress breast cancer metastasis. Nature. 2008;451:147–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Peng X, Guo W, Liu T, Wang X, Tu X, Xiong D, et al. Identification of miRs-143 and −145 that is associated with bone metastasis of prostate cancer and involved in the regulation of EMT. PLoS One. 2011;6:27.

    Google Scholar 

  33. Huang S, Guo W, Tang Y, Ren D, Zou X, Peng X. miR-143 and miR-145 inhibit stem cell characteristics of PC-3 prostate cancer cells. Oncol Rep. 2012;28:1831–7.

    CAS  PubMed  Google Scholar 

  34. Zhang HL, Qin XJ, Cao DL, Zhu Y, Yao XD, Zhang SL, et al. An elevated serum miR-141 level in patients with bone-metastatic prostate cancer is correlated with more bone lesions. Asian J Androl. 2013;15:231–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Huang Q, Gumireddy K, Schrier M, le Sage C, Nagel R, Nair S, et al. The microRNAs miR-373 and miR-520c promote tumour invasion and metastasis. Nat Cell Biol. 2008;10:202–10.

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Hua Xin.

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Han, C., Yu, H., Zhang, L. et al. MicroRNAs used as novel biomarkers for detecting cancer metastasis. Tumor Biol. 36, 1755–1762 (2015). https://doi.org/10.1007/s13277-014-2777-0

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