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Plasma long noncoding RNA protected by exosomes as a potential stable biomarker for gastric cancer

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Tumor Biology

Abstract

Long intergenic non-protein-coding RNA 152 (LINC00152) is one of the long noncoding RNAs (lncRNAs) abnormally expressed in gastric cancer tissues. However, its value in the diagnosis of gastric cancer is unclear. The aim of this study is to evaluate the clinical significance of plasma LINC00152 as a biomarker in the screening of gastric cancer and to explore the possible mechanism underling its stable existence in blood. We analyzed the levels of plasma LINC00152 in patients with gastric cancer and gastric epithelial dysplasia and healthy controls using quantitative reverse transcription polymerase chain reaction and then confirmed by sequencing. We also compared its levels in paired preoperative and postoperative plasma samples. In addition, we compared the levels of LINC00152 in plasma and in exosomes, which were extracted from the same plasma and confirmed by transmission electron microscopy. The levels of plasma LINC00152 were significantly elevated in gastric cancer patients compared with healthy controls. The sensitivity and specificity of plasma LINC00152 in the diagnosis of gastric cancer were 48.1 and 85.2 %, respectively. There were no significant differences of LINC00152 levels between gastric epithelial dysplasia patients and healthy controls. LINC00152 levels in preoperative plasma samples were lower than those in postoperative ones. There were also no differences between LINC00152 levels in plasma and in exosomes. All these results suggested that LINC00152 can be detected in plasma, and one of the possible mechanisms of its stable existence in blood was protected by exosomes. It has the possibility to be applied in gastric cancer diagnosis as a novel blood-based biomarker.

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References

  1. Ferlay J, Shin HR, Bray F, Forman D, Mather C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127:2893–917.

    Article  CAS  PubMed  Google Scholar 

  2. Maruyama R, Suzuki H. Long noncoding RNA involvement in cancer. BMB Rep. 2012;45:604–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Qi P, Du X. The long non-coding RNAs, a new cancer diagnostic and therapeutic gold mine. Mod Pathol. 2013;26:155–65.

    Article  CAS  PubMed  Google Scholar 

  4. Yang F, Bi J, Xue X, Zheng L, Zhi K, Hua J, et al. Up-regulated long non-coding RNA H19 contributes to proliferation of gastric cancer cells. FEBS J. 2012;279:3159–65.

    Article  CAS  PubMed  Google Scholar 

  5. Mei D, Song H, Wang K, Lou Y, Sun W, Liu Z, et al. Up-regulation of SUMO1 pseudogene 3 (SUMO1P3) in gastric cancer and its clinical association. Med Oncol. 2013;30:709.

    Article  PubMed  Google Scholar 

  6. Sun W, Wu Y, Yu X, Liu Y, Song H, Xia T, et al. Decreased expression of long noncoding RNA AC096655.1-002 in gastric cancer and its clinical significance. Tumour Biol. 2013;34:2697–701.

    Article  CAS  PubMed  Google Scholar 

  7. Xiao B, Guo J. Long noncoding RNA AC096655.1-002 has been officially named as gastric cancer-associated transcript 1, GACAT1. Tumour Biol. 2013;4:3271.

    Article  Google Scholar 

  8. Song H, Sun W, Ye G, Ding X, Liu Z, Zhang S, et al. Long non-coding RNA expression profile in human gastric cancer and its clinical significances. J Transl Med. 2013;11:225.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Arita T, Ichikawa D, Konishi H, Komatsu S, Shiozaki A, Shoda K, et al. Circulating long non-coding RNAs in plasma of patients with gastric cancer. Anticancer Res. 2013;33:3185–93.

    CAS  PubMed  Google Scholar 

  10. Tang H, Wu Z, Zhang J, Su B. Salivary lncRNA as a potential marker for oral squamous cell carcinoma diagnosis. Mol Med Rep. 2013;7:761–6.

    CAS  PubMed  Google Scholar 

  11. Hessels D, Klein Gunnewiek JM, Van Oort I, Karthaus HF, van Leenders GJ, van Balken B, et al. DD3(PCA3)-based molecular urine analysis for the diagnosis of prostate cancer. Eur Urol. 2003;44:8–16.

    Article  CAS  PubMed  Google Scholar 

  12. Pang Q, Ge J, Shao Y, Sun W, Song H, Xia T, et al. Increased expression of long intergenic non-coding RNA LINC00152 in gastric cancer and its clinical significance. Tumour Biol. 2014;35:5441–7.

    Article  CAS  PubMed  Google Scholar 

  13. Washington K. 7th edition of the AJCC cancer staging manual: stomach. Ann Surg Oncol. 2010;17:3077–9.

    Article  PubMed  Google Scholar 

  14. Orozco AF, Lewis DE. Flow cytometric analysis of circulating microparticles in plasma. Cytometry A. 2010;77:502–14.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Record M, Subra C, Silvente-Poirot S, Poirot M. Exosomes as intercellular signalosomes and pharmacological effectors. Biochem Pharmacol. 2011;81:1171–82.

    Article  CAS  PubMed  Google Scholar 

  16. Bagaria B, Sood S, Sharma R, Lalwani S. Comparative study of CEA and CA19-9 in esophageal, gastric and colon cancers individually and in combination (ROC curve analysis). Cancer Biol Med. 2013;10:148–57.

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Ferreiral LB, Palumbo A, de Mello KD, Sternberg C, Caetano MS, de Oliveira FL, et al. PCA3 noncoding RNA is involved in the control of prostate-cancer cell survival and modulates androgen receptor signaling. BMC Cancer. 2012;12:507.

    Article  Google Scholar 

  18. Gutschner T, Hämmerle 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.

    Article  CAS  PubMed  Google Scholar 

  19. Shao Y, Chen H, Jiang X, Chen S, Li P, Ye M, et al. Low expression of lncRNA-HMlincRNA717 in human gastric cancer and its clinical significances. Tumour Biol. 2014. doi:10.1007/s13277-014-2243-z.

    Google Scholar 

  20. Xu C, Shao Y, Xia T, Yang Y, Dai J, Luo L, et al. lncRNA-AC130710 targeting by miR-129-5p is upregulated in gastric cancer and associates with poor prognosis. Tumour Biol. 2014. doi:10.1007/s13277-014-2274-5.

    Google Scholar 

  21. Chen S, Li P, Xiao B, Guo J. Long noncoding RNA HMlincRNA717 and AC130710 have been officially named as gastric cancer associated transcript 2 (GACAT2) and GACAT3, respectively. Tumour Biol. 2014;35:8351–2.

    Article  PubMed  Google Scholar 

  22. Lee GL, Dobi A, Srivastava S. Prostate cancer: diagnostic performance of the PCA3 urine test. Nat Rev Urol. 2011;8:123–4.

    Article  PubMed  Google Scholar 

  23. Tinzl M, Marberger M, Horvath S, Chypre C. DD3PCA3 RNA analysis in urine-a new perspective for detecting prostate cancer. Eur Urol. 2004;46:182–7.

    Article  CAS  PubMed  Google Scholar 

  24. 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.

    Article  CAS  PubMed  Google Scholar 

  25. Huang X, Yuan T, Tschannen M, Sun Z, Jacob H, Du M, et al. Characterization of human plasma-derived exosomal RNAs by deep sequencing. BMC Genomics. 2013;14:319.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

This work was supported by the Zhejiang Provincial Natural Science Foundation of China (No. LY14C060003), the Applied Research Project on Nonprofit Technology of Zhejiang Province (No. 2014C33222), the National Natural Science Foundation of China (No. 81171660), the Natural Science Foundation of Ningbo (No. 2013A610206), the Scientific Innovation Team Project of Ningbo (No. 2011B82014), the Open Foundation of the Zhejiang Provincial Key Laboratory of Pathophysiology (No. 201302), the Scientific Research Project of Ningbo University (No. XYY13002), and the K. C. Wong Magna Fund in Ningbo University.

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Correspondence to Guoliang Ye or Bingxiu Xiao.

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Li, Q., Shao, Y., Zhang, X. et al. Plasma long noncoding RNA protected by exosomes as a potential stable biomarker for gastric cancer. Tumor Biol. 36, 2007–2012 (2015). https://doi.org/10.1007/s13277-014-2807-y

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  • DOI: https://doi.org/10.1007/s13277-014-2807-y

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