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Prognostic Significance of MicroRNA-16 Expression in Human Colorectal Cancer

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Abstract

Background

MicroRNAs (miRNAs), small noncoding RNAs, have been reported to be highly involved in the formation and progression of all types of human cancer including colorectal cancer (CRC). Therefore, miRNAs are also potential prognostic biomarkers in CRC patients. The aim of this study was to detect the expression of miR-16 in human CRC tissues and investigate its clinicopathologic or prognostic significance.

Methods

TaqMan quantitative reverse transcription polymerase chain reaction (qRT-PCR) assay was performed to determine the expression of miR-16 in 143 primary CRC tissues and 18 corresponding normal colonic mucosa from patients who had undergone surgery. The association of miR-16 expression with clinicopathologic features of CRC patients was statistically analyzed. Kaplan–Meier analyses were used to assess patient survival. Univariate and multivariate Cox analyses were performed.

Results

The relative level of miR-16 in 18 CRC tissues was significantly lower than that in corresponding normal colonic mucosa (p < 0.001). Statistical analyses revealed that the status of miR-16 expression was closely associated with tumor differentiation, lymph node metastasis, L category, V category, TNM stage, and tumor recurrence of CRC (p = 0.001, 0.003, 0.001, 0.005, 0.003, and 0.017, respectively). Kaplan–Meier analyses indicated that patients with low-miR-16 had lower 5-year overall survival than those with high-miR-16 (31.2 vs. 58.3 %; p = 0.0012). Multivariate Cox regression analyses indicated that the status of miR-16 expression might be an independent prognostic factor for CRC patients (hazard ratio 1.67; 95 % confidence interval 1.22–2.54; p = 0.018).

Conclusions

Down-regulation of miR-16 plays critical roles in CRC progression. Low miR-16 expression is an independent factor predicting a poor prognosis for CRC patients.

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References

  1. Center MM, Jemal A, Smith RA et al (2009) Worldwide variations in colorectal cancer. CA Cancer J Clin 59:366–378

    Article  PubMed  Google Scholar 

  2. Bolocan A, Ion D, Ciocan DN et al (2012) Prognostic and predictive factors in colorectal cancer. Chirurgia (Bucur) 107:555–563

    CAS  Google Scholar 

  3. Ke XS, Liu CM, Liu DP et al (2003) MicroRNAs: key participants in gene regulatory networks. Curr Opin Chem Biol 7:516–523

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  5. Jansson MD, Lund AH (2012) MicroRNA and cancer. Mol Oncol 6:590–610

    Article  PubMed  CAS  Google Scholar 

  6. Shen J, Stass SA, Jiang F (2013) MicroRNAs as potential biomarkers in human solid tumors. Cancer Lett 329:125–136

    Article  PubMed  CAS  Google Scholar 

  7. Garzon R, Marcucci G (2012) Potential of microRNAs for cancer diagnostics, prognostication and therapy. Curr Opin Oncol 24:655–659

    Article  PubMed  CAS  Google Scholar 

  8. Takeshita F, Patrawala L, Osaki M (2010) Systemic delivery of synthetic microRNA-16 inhibits the growth of metastatic prostate tumors via downregulation of multiple cell-cycle genes. Mol Ther 18:181–187

    Article  PubMed  CAS  Google Scholar 

  9. Agra Andrieu N, Motiño O, Mayoral R (2012) Cyclooxygenase-2 is a target of microRNA-16 in human hepatoma cells. PLoS One 7:e50935

    Article  PubMed  CAS  Google Scholar 

  10. Ma Q, Wang X, Li Z et al (2013) microRNA-16 represses colorectal cancer cell growth in vitro by regulating the p53/survivin signaling pathway. Oncol Rep 29:1652–1658

    PubMed  CAS  Google Scholar 

  11. Bendardaf R, Lamlum H, Pyrhönen S (2004) Prognostic and predictive molecular markers in colorectal carcinoma. Anticancer Res 24:2519–2530

    PubMed  CAS  Google Scholar 

  12. Pasche B, Mulcahy M, Benson AB 3rd (2002) Molecular markers in prognosis of colorectal cancer and prediction of response to treatment. Best Pract Res Clin Gastroenterol 16:331–345

    Article  PubMed  CAS  Google Scholar 

  13. Schetter AJ, Okayama H, Harris CC (2012) The role of microRNAs in colorectal cancer. Cancer J 18:244–252

    Article  PubMed  CAS  Google Scholar 

  14. Corté H, Manceau G, Blons H et al (2012) MicroRNA and colorectal cancer. Dig Liver Dis 44:195–200

    Article  PubMed  Google Scholar 

  15. Weiland M, Gao XH, Zhou L et al (2012) Small RNAs have a large impact: circulating microRNAs as biomarkers for human diseases. RNA Biol 9:850–859

    Article  PubMed  CAS  Google Scholar 

  16. Zhou L, Zhao YP, Liu WJ et al (2012) Circulating microRNAs in cancer: diagnostic and prognostic significance. Expert Rev Anticancer Ther 12:283–288

    Article  PubMed  CAS  Google Scholar 

  17. Li J, Du L, Yang Y et al (2013) MiR-429 is an independent prognostic factor in colorectal cancer and exerts its anti-apoptotic function by targeting SOX2. Cancer Lett 329:84–90

    Article  PubMed  CAS  Google Scholar 

  18. Nishimura J, Handa R, Yamamoto H et al (2012) MicroRNA-181a is associated with poor prognosis of colorectal cancer. Oncol Rep 28:2221–2226

    PubMed  CAS  Google Scholar 

  19. Wang Q, Huang Z, Ni S et al (2012) Plasma miR-601 and miR-760 are novel biomarkers for the early detection of colorectal cancer. PLoS One 7:e44398

    Article  PubMed  CAS  Google Scholar 

  20. Pichler M, Winter E, Stotz M et al (2012) Down-regulation of KRAS-interacting miRNA-143 predicts poor prognosis but not response to EGFR-targeted agents in colorectal cancer. Br J Cancer 106:1826–1832

    Article  PubMed  CAS  Google Scholar 

  21. Xi Y, Li J, Zan L et al (2013) Micro-RNA-16 expression in paraffin-embedded specimen correlates with overall survival of T-lymphoblastic lymphoma/leukemia. Hum Pathol 44:1011–1016

    Article  PubMed  CAS  Google Scholar 

  22. Navarro A, Diaz T, Gallardo E et al (2011) Prognostic implications of miR-16 expression levels in resected non-small-cell lung cancer. J Surg Oncol 103:411–415

    Article  PubMed  CAS  Google Scholar 

  23. Gao X, Zhang R, Qu X et al (2012) MiR-15a, miR-16-1 and miR-17-92 cluster expression are linked to poor prognosis in multiple myeloma. Leuk Res 36:1505–1509

    Article  PubMed  CAS  Google Scholar 

  24. Wu H, Liu T, Wang R et al (2011) MicroRNA-16 targets zyxin and promotes cell motility in human laryngeal carcinoma cell line HEp-2. IUBMB Life 63:101–108

    PubMed  CAS  Google Scholar 

  25. McShane LM, Altman DG, Sauerbrei W et al (2005) REporting recommendations for tumour MARKer prognostic studies (REMARK). Eur J Cancer 41:1690–1696

    Article  PubMed  Google Scholar 

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Acknowledgments

The authors thank Professor Ming Zhang for expert advice on pathology. We also thank everyone in the Department of Pathology for their technical assistance.

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Correspondence to Mingzhi Fang.

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268_2013_2205_MOESM1_ESM.tif

Supplementary Fig. S1 A ROC curve for survival prediction was plotted to identify the optimum cutoff point for miR-16 in CRC, which was 0.52. The area under the curve for miR-16 was 70.5 % (95 % confidence interval 0.678–0.768) with sensitivity of 63.6 % and specificity of 74.4 % (p = 0.012) Supplementary material 1 (TIFF 14 kb)

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Qian, J., Jiang, B., Li, M. et al. Prognostic Significance of MicroRNA-16 Expression in Human Colorectal Cancer. World J Surg 37, 2944–2949 (2013). https://doi.org/10.1007/s00268-013-2205-4

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  • DOI: https://doi.org/10.1007/s00268-013-2205-4

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