Tumor Biology

, Volume 36, Issue 12, pp 9909–9918 | Cite as

Combination of miRNA and RNA functions as potential biomarkers for gastric cancer

  • Silin Chen
  • Jiaming Zhu
  • Feifei Yu
  • Yuxi Tian
  • Shumei Ma
  • Xiaodong Liu
Research Article

Abstract

Gastric cancer (GC) is the second leading cause of cancer-related death in the world. The optimal treatment regimens for GC depend on tumor stage, histopathological subtype, and other factors. The detection of tumor biomarkers is a quick way to get information of the tumor state. In this study, new biomarkers are detected for GC diagnostic and prognostic purposes. A total of 305 cases of diagnosed gastric adenocarcinoma were enrolled, microRNAs (miRNAs) and their transcriptome sequencing data were obtained from the “The Cancer Genome Atlas.” Blood samples were collected from GC patients before surgery and therapy. The miRNA levels and the expression of RNA were detected by real-time RT-PCR. Receiver operating characteristic analysis was used to evaluate the sensitivity and specificity of biomarkers. The combining predictors were established with the logistic regression analysis. Hundreds of miRNA were with higher area under curve (AUC) than 0.5; among them, nine miRNAs were with the highest AUC more than 0.90 and displayed strong diagnostic value. Moreover, the mir-17 level was correlated with tumor stage (p = 0.029), while mir-133b, mir-133a-2, and mir-1-2 levels were significantly correlated with race, tumor pathologic, and tumor stage (p < 0.05). The combination biomarker (mir-181a-1/KAT2B with a sensitivity of 95.83 % and specificity of 94.12 %) could be used as an independent diagnostic indicator for GC patients. For GC patients, mir-17, mir-133b, mir-133a-2, and mir-1-2 appear to be a potential novel predictor of tumor stage and preoperative and intraoperative diagnosis. The combination of miRNA and mRNA such as mir-181a-1/KAT2B (with a sensitivity of 95.83 % and specificity of 94.12 %) showed significant improvement in the diagnostic accuracy.

Keywords

Gastric cancer Diagnosis miRNA mRNA ROC 

Notes

Acknowledgments

Thanks are given to Lizann Oswald for the revision of this manuscript. This study was supported by NSFC grant (30770649, 30970682, 31370837), Research Fund for Science and Technology Program of Jilin Province (20150101142JC), Ministry of Health of Jilin Province (20142036), Health and Family Planning Commission of Jilin Province (20142036), and Natural Science Foundation of Jilin Province (20150101142JC).

Statement of human rights

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Conflicts of interest

None

References

  1. 1.
    Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.CrossRefPubMedGoogle Scholar
  2. 2.
    Zhao JJ, Pan K, Wang W, Chen JG, Wu YH, Lv L. The prognostic value of tumor-infiltrating neutrophils in gastric adenocarcinoma after resection. PLoS One. 2012;7:e33655.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Bertuccio P, Chatenoud L, Levi F, Praud D, Ferlay J, Negri E, et al. Recent patterns in gastric cancer: a global overview. Int J Cancer. 2009;125:666–73.CrossRefPubMedGoogle Scholar
  4. 4.
    Tan YK, Fielding JW. Early diagnosis of early gastric cancer. Eur J Gastroenterol Hepatol. 2006;18:821–9.CrossRefPubMedGoogle Scholar
  5. 5.
    Kaise M, Kimura R, Nomura K, Kuribayashi Y, Kikuchi D, Iizuka T et al.: Accuracy and concordance of endocytoscopic atypia for the diagnosis of gastric cancer. Endoscopy 2014Google Scholar
  6. 6.
    He CZ, Zhang KH, Li Q, Liu XH, Hong Y, Lv NH. Combined use of AFP, CEA, CA125 and CAL9-9 improves the sensitivity for the diagnosis of gastric cancer. BMC Gastroenterol. 2013;13:87.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Marrelli D, Pinto E, De Stefano A, Farnetani M, Garosi L, Roviello F. Clinical utility of CEA, CA 19-9, and CA 72-4 in the follow-up of patients with resectable gastric cancer. Am J Surg. 2001;181:16–9.CrossRefPubMedGoogle Scholar
  8. 8.
    Zhu YB, Ge SH, Zhang LH, Wang XH, Xing XF, Du H, et al. Clinical value of serum CEA, CA19-9, CA72-4 and CA242 in the diagnosis and prognosis of gastric cancer. J Gastrointestinal Surg. 2012;15:161–4.Google Scholar
  9. 9.
    Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116:281–97.CrossRefPubMedGoogle Scholar
  10. 10.
    Sassen S, Miska EA, Caldas C. MicroRNA: implications for cancer. Virchows Arch. 2008;452:1–10.CrossRefPubMedGoogle Scholar
  11. 11.
    Zhu C, Ren C, Han J, Ding Y, Du J, Dai N, et al. A five-microRNA panel in plasma was identified as potential biomarker for early detection of gastric cancer. Br J Cancer. 2014;110(9):2291–9.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Su ZX, Zhao J, Rong ZH, Wu YG, Geng WM, Qin CK. Diagnostic and prognostic value of circulating miR-18a in the plasma of patients with gastric cancer. Tumour Biol. 2014;35(12):12119–25.CrossRefPubMedGoogle Scholar
  13. 13.
    Kamangar F, Dores GM, Anderson WF. Patterns of cancer incidence, mortality, and prevalence across five continents: defining priorities to reduce cancer disparities in different geographic regions of the world. J Clin Oncol. 2006;24:2137–50.CrossRefPubMedGoogle Scholar
  14. 14.
    Kim DY, Joo JK, Ryu SY, Kim YJ, Kim SK. Factors related to lymph node metastasis and surgical strategy used to treat early gastric carcinoma. World J Gastroenterol. 2004;10:737–40.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Inoue H, Kudo SE, Shiokawa A. Technology insight: laser-scanning confocal microscopy and endocytoscopy for cellular observation of the gastrointestinal tract. Nat Clin Pract Gastroenterol Hepatol. 2005;2:31–7.CrossRefPubMedGoogle Scholar
  16. 16.
    Neumann H, Fuchs FS, Vieth M, Atreya R, Siebler J, Kiesslich R, et al. Review article: in vivo imaging by endocytoscopy. Aliment Pharmacol Ther. 2011;33:1183–93.CrossRefPubMedGoogle Scholar
  17. 17.
    Kumagai Y, Monma K, Kawada K. Magnifying chromoendoscopy of the esophagus: in-vivo pathological diagnosis using an endocytoscopy system. Endoscopy. 2004;36:590–4.CrossRefPubMedGoogle Scholar
  18. 18.
    Pinheiro DD, Ferreira WA, Barros MB, Araujo MD, Rodrigues-Antunes S, Borges BD. Perspectives on new biomarkers in gastric cancer: diagnostic and prognostic applications. World J Gastroenterol. 2014;20:11574–85.CrossRefPubMedCentralGoogle Scholar
  19. 19.
    Zhang Y, Han T, Wei G, Wang Y. Inhibition of microRNA-17/20a suppresses cell proliferation in gastric cancer by modulating UBE2C expression. Oncol Rep. 2015;33:2529–36.PubMedGoogle Scholar
  20. 20.
    Han C, Zhou Y, An Q, Li F, Li D, Zhang X, et. al: MicroRNA-1 (mir-1) inhibits gastric cancer cell proliferation and migration by targeting MET. Tumour biology: the journal of the International Society for Oncodevelopmental Biology and Medicine 2015Google Scholar
  21. 21.
    Qiu T, Zhou X, Wang J, Du Y, Xu J, Huang Z, et al. Mir-145, mir-133a and mir-133b inhibit proliferation, migration, invasion and cell cycle progression via targeting transcription factor sp1 in gastric cancer. FEBS Lett. 2014;588:1168–77.CrossRefPubMedGoogle Scholar
  22. 22.
    Zeng Q, Jin C, Chen W, Xia F, Wang Q, Fan F, et al. Downregulation of serum mir-17 and mir-106b levels in gastric cancer and benign gastric diseases. J Cancer Res. 2014;26:711–6.Google Scholar
  23. 23.
    Xin SY, Feng XS, Zhou LQ, Sun JJ, Gao XL, Yao GL. Reduced expression of circulating microRNA-218 in gastric cancer and correlation with tumor invasion and prognosis. World J Gastroenterol. 2014;20:6906–11.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Silin Chen
    • 1
  • Jiaming Zhu
    • 2
  • Feifei Yu
    • 1
  • Yuxi Tian
    • 1
  • Shumei Ma
    • 1
    • 3
  • Xiaodong Liu
    • 1
    • 4
  1. 1.Key Laboratory of Radiobiology (Ministry of Health), School of Public HealthJilin UniversityChangchunChina
  2. 2.2nd Hospital Jilin UniversityChangchunChina
  3. 3.Institute of Cancer CareUniversity of ManitobaWinnipegCanada
  4. 4.Center for Radiological ResearchColumbia UniversityNew YorkUSA

Personalised recommendations