Skip to main content

Advertisement

Log in

Circulating long noncoding RNA GAS5 as a potential biomarker in breast cancer for assessing the surgical effects

  • Original Article
  • Published:
Tumor Biology

Abstract

Long noncoding RNAs (lncRNAs) play a vital role in tumorigenesis. Until now, the value of circulating lncRNAs in the diagnosis of breast cancer (BC) has remained unknown. Here, we have explored the clinical significance of lncRNAs GAS5 and H19 in BC patients. Total RNA in the plasma was extracted from 90 preoperative BC patients, 39 postoperative BC patients, and 76 healthy controls. The expression levels were measured by quantitative real-time PCR. The potential associations between GAS5, H19 levels, and patients’ clinical characteristics were analyzed. No significant differences were found between the BC patients and the healthy controls in the expression levels of GAS5 (P = 0.441) and H19 (P = 0.554), normalized by GAPDH. Plasma GAS5 exhibited correlations with the Ki67 proliferation index in 90 preoperative BC patients (P = 0.012). Compared with paired preoperative plasma, the postoperative levels of GAS5 and H19 significantly decreased in 71.8 % of BC patients (28/39) and 82.1 % of BC patients (32/39), respectively. Analysis in the 39 paired preoperative and postoperative plasma samples showed that lower GAS5 levels appeared in the patients with a high Ki67 proliferation index before surgery (P = 0.012) and the patients with a positive lymph node metastasis state after surgery (P = 0.029). Plasma lncRNA GAS5 may have the potential to assess the surgical effects and prognosis for BC patients.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136:E359–86.

    Article  CAS  PubMed  Google Scholar 

  2. Screening for breast cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2009;151:716–726, 236.

  3. Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, et al. MicroRNA expression profiles classify human cancers. Nature. 2005;435:834–8.

    Article  CAS  PubMed  Google Scholar 

  4. Liu H. MicroRNAs in breast cancer initiation and progression. Cell Mol Life Sci. 2012;69:3587–99.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Li P, Xie XB, Chen Q, Pang GL, Luo W, Tu JC, et al. MiRNA-15a mediates cell cycle arrest and potentiates apoptosis in breast cancer cells by targeting synuclein-gamma. Asian Pac J Cancer Prev. 2014;15:6949–54.

    Article  PubMed  Google Scholar 

  6. Qi JH, Wang J, Chen J, Shen F, Huang JT, Sen S, et al. High-resolution melting analysis reveals genetic polymorphisms in microRNAs confer hepatocellular carcinoma risk in Chinese patients. BMC Cancer. 2014;14:643.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Wang J, Zhang KY, Liu SM, Sen S. Tumor-associated circulating microRNAs as biomarkers of cancer. Molecules. 2014;19:1912–38.

    Article  PubMed  Google Scholar 

  8. Inns J., James V. Circulating microRNAs for the prediction of metastasis in breast cancer patients diagnosed with early stage disease. Breast. 2015.

  9. Wozniak MB, Scelo G, Muller DC, Mukeria A, Zaridze D, Brennan P. Circulating microRNAs as non-invasive biomarkers for early detection of non-small-cell lung cancer. PLoS One. 2015;10, e125026.

    Article  Google Scholar 

  10. Qi J, Wang J, Katayama H, Sen S, Liu SM. Circulating microRNAs (cmiRNAs) as novel potential biomarkers for hepatocellular carcinoma. Neoplasma. 2013;60:135–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Huang JT, Liu SM, Ma H, Yang Y, Zhang X, Sun H, et al. Systematic review and meta-analysis: circulating miRNAs for diagnosis of hepatocellular carcinoma. J Cell Physiol. 2015.

  12. Brunner AL, Beck AH, Edris B, Sweeney RT, Zhu SX, Li R, et al. Transcriptional profiling of long non-coding RNAs and novel transcribed regions across a diverse panel of archived human cancers. Genome Biol. 2012;13:R75.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Spizzo R, Almeida MI, Colombatti A, Calin GA. Long non-coding RNAs and cancer: a new frontier of translational research? Oncogene. 2012;31:4577–87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Prensner JR, Chinnaiyan AM. The emergence of lncRNAs in cancer biology. Cancer Discov. 2011;1:391–407.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Crea F, Watahiki A, Quagliata L, Xue H, Pikor L, Parolia A, et al. Identification of a long non-coding RNA as a novel biomarker and potential therapeutic target for metastatic prostate cancer. Oncotarget. 2014;5:764–74.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Dong L, Qi P, Xu MD, Ni SJ, Huang D, Xu QH, et al. Circulating CUDR, LSINCT-5 and PTENP1 long noncoding RNAs in sera distinguish patients with gastric cancer from healthy controls. Int J Cancer. 2015.

  17. Tong YS, Wang XW, Zhou XL, Liu ZH, Yang TX, Shi WH, et al. Identification of the long non-coding RNA POU3F3 in plasma as a novel biomarker for diagnosis of esophageal squamous cell carcinoma. Mol Cancer. 2015;14:3.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Zhou X, Yin C, Dang Y, Ye F, Zhang G. Identification of the long non-coding RNA H19 in plasma as a novel biomarker for diagnosis of gastric cancer. Sci Rep. 2015;5:11516.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Chen G, Wang Z, Wang D, Qiu C, Liu M, Chen X, et al. LncRNADisease: a database for long-non-coding RNA-associated diseases. Nucleic Acids Res. 2013;41:D983–6.

    Article  CAS  PubMed  Google Scholar 

  20. Shao Y, Ye M, Jiang X, Sun W, Ding X, Liu Z, et al. Gastric juice long noncoding RNA used as a tumor marker for screening gastric cancer. Cancer. 2014;120:3320–8.

    Article  CAS  PubMed  Google Scholar 

  21. Uchida S, Dimmeler S. Long noncoding RNAs in cardiovascular diseases. Circ Res. 2015;116:737–50.

    Article  CAS  PubMed  Google Scholar 

  22. Ng SY, Lin L, Soh BS, Stanton LW. Long noncoding RNAs in development and disease of the central nervous system. Trends Genet. 2013;29:461–8.

    Article  CAS  PubMed  Google Scholar 

  23. Gibb EA, Brown CJ, Lam WL. The functional role of long non-coding RNA in human carcinomas. Mol Cancer. 2011;10:38.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Pickard MR, Williams GT. Regulation of apoptosis by long non-coding RNA GAS5 in breast cancer cells: implications for chemotherapy. Breast Cancer Res Treat. 2014;145:359–70.

    Article  CAS  PubMed  Google Scholar 

  26. Lottin S, Adriaenssens E, Dupressoir T, Berteaux N, Montpellier C, Coll J, et al. Overexpression of an ectopic H19 gene enhances the tumorigenic properties of breast cancer cells. Carcinogenesis. 2002;23:1885–95.

    Article  CAS  PubMed  Google Scholar 

  27. Silva JM, Boczek NJ, Berres MW, Ma X, Smith DI. LSINCT5 is over expressed in breast and ovarian cancer and affects cellular proliferation. RNA Biol. 2011;8:496–505.

    Article  CAS  PubMed  Google Scholar 

  28. Shi Y, Lu J, Zhou J, Tan X, He Y, Ding J, et al. Long non-coding RNA Loc554202 regulates proliferation and migration in breast cancer cells. Biochem Biophys Res Commun. 2014;446:448–53.

    Article  CAS  PubMed  Google Scholar 

  29. Godinho MF, Sieuwerts AM, Look MP, Meijer D, Foekens JA, Dorssers LC, et al. Relevance of BCAR4 in tamoxifen resistance and tumour aggressiveness of human breast cancer. Br J Cancer. 2010;103:1284–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Mourtada-Maarabouni M, Pickard MR, Hedge VL, Farzaneh F, Williams GT. GAS5, a non-protein-coding RNA, controls apoptosis and is downregulated in breast cancer. Oncogene. 2009;28:195–208.

    Article  CAS  PubMed  Google Scholar 

  31. Matouk IJ, DeGroot N, Mezan S, Ayesh S, Abu-lail R, Hochberg A, et al. The H19 non-coding RNA is essential for human tumor growth. PLoS One. 2007;2, e845.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Sun M, Jin FY, Xia R, Kong R, Li JH, Xu TP, et al. Decreased expression of long noncoding RNA GAS5 indicates a poor prognosis and promotes cell proliferation in gastric cancer. BMC Cancer. 2014;14:319.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Shi X, Sun M, Liu H, Yao Y, Kong R, Chen F, et al. A critical role for the long non-coding RNA GAS5 in proliferation and apoptosis in non-small-cell lung cancer. Mol Carcinog. 2015;54 Suppl 1:E1–12.

    Article  CAS  PubMed  Google Scholar 

  34. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Quek XC, Thomson DW, Maag JL, Bartonicek N, Signal B, Clark MB, et al. LncRNAdb v2.0: expanding the reference database for functional long noncoding RNAs. Nucleic Acids Res. 2015;43:D168–73.

    Article  PubMed  Google Scholar 

  36. Ahlin C, Aaltonen K, Amini RM, Nevanlinna H, Fjallskog ML, Blomqvist C. Ki67 and cyclin a as prognostic factors in early breast cancer. What are the optimal cut-off values? Histopathology. 2007;51:491–8.

    Article  CAS  PubMed  Google Scholar 

  37. Mu K, Li L, Yang Q, Yun H, Kharaziha P, Ye DW, et al. A standardized method for quantifying proliferation by Ki-67 and cyclin A immunohistochemistry in breast cancer. Ann Diagn Pathol. 2015.

  38. Liu Z, Shao Y, Tan L, Shi H, Chen S, Guo J. Clinical significance of the low expression of FER1L4 in gastric cancer patients. Tumour Biol. 2014;35:9613–7.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by the National Basic Research Program of China (973 Program) (2012CB720600, 2012CB720605).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Xin Zhou.

Ethics declarations

Conflicts of interest

None

Electronic supplementary material

Below is the link to the electronic supplementary material.

ESM 1

(PDF 1862 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Han, L., Ma, P., Liu, SM. et al. Circulating long noncoding RNA GAS5 as a potential biomarker in breast cancer for assessing the surgical effects. Tumor Biol. 37, 6847–6854 (2016). https://doi.org/10.1007/s13277-015-4568-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-015-4568-7

Keywords

Navigation