Skip to main content

Advertisement

SpringerLink
Log in

Serum miR-182 and miR-331-3p as diagnostic and prognostic markers in patients with hepatocellular carcinoma

  • Research Article
  • Published:
Tumor Biology

Abstract

Previous studies have identified a number of microRNAs (miRNAs) that were aberrantly expressed in hepatocellular carcinoma (HCC) tissues. Nevertheless, their diagnostic and prognostic value in serum has not been fully evaluated. Herein, the levels of five serum miRNAs, namely, miR-182, miR-331-3p, miR-197, miR-492, and miR-581, were detected in 103 HCC patients, 95 benign liver diseases, and 40 healthy controls using real-time PCR technique. The results showed that, compared with benign liver diseases and healthy controls, the levels of serum miR-182 and miR-331-3p were significantly increased in HCC patients, both P < 0.001. Area under the receiver–operating characteristic (ROC) curves for serum miR-182 and miR-331-3p were 0.911 (95 % CI, 0.863–0.947) and 0.890 (95 % CI, 0.838–0.930), the sensitivity were 78.6 and 79.61 %, and the specificity were 91.58 and 86.32 %, respectively. Moreover, the combination of serum miR-182, miR-331-3p, and alpha-fetoprotein (AFP) can markedly increase the differential diagnostic value of benign and malignant liver diseases, especially better than serum AFP alone, P < 0.05. Serum miR-182 was positively correlated with serum AFP (P = 0.001), tumor size (P = 0.013), and TNM classification of malignant tumors (TNM) stage (P = 0.003); however, only TNM stage was demonstrated a significant correlation with serum miR-331-3p (P = 0.006). In addition, Kaplan–Meier survival curve, together with univariate and multivariate Cox proportional hazard analyses, further disclosed that serum miR-182 and miR-331-3p were associated with postoperative survival of HCC patients, and both of them were regarded to be independent prognostic factors for patients with HCC. Taken together, our present study indicates that serum miR-182 and miR-331-3p, upregulated in HCC, can provide positive diagnostic and prognostic values for HCC.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Bruix J, Gores GJ, Mazzaferro V. Hepatocellular carcinoma: clinical frontiers and perspectives. Gut. 2014;63:844–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Xu WJ, Guo BL, Han YG, Shi L, Ma WS. Diagnostic value of alpha- fetoprotein-L3 and Golgi protein 73 in hepatocellular carcinomas with low AFP levels. Tumour Biol. 2014;35(12):12069–74.

    Article  CAS  PubMed  Google Scholar 

  3. Debruyne EN, Delanghe JR. Diagnosing and monitoring hepatocellular carcinoma with alpha-fetoprotein: new aspects and applications. Clin Chim Acta. 2008;395(1–2):19–26.

    Article  CAS  PubMed  Google Scholar 

  4. Park H, Park JY. Clinical significance of AFP and PIVKA-II responses for monitoring treatment outcomes and predicting prognosis in patients with hepatocellular carcinoma. Biomed Res Int. 2013;2013:310427.

    PubMed  PubMed Central  Google Scholar 

  5. Giannini EG, Sammito G, Farinati F, Ciccarese F, Pecorelli A, Rapaccini GL, et al. Determinants of alpha-fetoprotein levels in patients with hepatocellular carcinoma: implications for its clinical use. Cancer. 2014;120(14):2150–7.

    Article  CAS  PubMed  Google Scholar 

  6. Han LL, Lv Y, Guo H, Ruan ZP, Nan KJ. Implications of biomarkers in human hepatocellular carcinoma pathogenesis and therapy. World J Gastroenterol. 2014;20:10249–61.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Raza A, Sood GK. Hepatocellular carcinoma review: current treatment, and evidence-based medicine. World J Gastroenterol. 2014;20:4115–27.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Tutar L, Tutar E, Tutar Y. MicroRNAs and cancer; an overview. Curr Pharm Biotechnol. 2014;15:430–7.

    Article  CAS  PubMed  Google Scholar 

  9. Berger F, Reiser MF. Micro-RNAs as potential new molecular biomarkers in oncology: have they reached relevance for the clinical imaging sciences? Theranostics. 2013;3:943–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Li B, Huang P, Qiu J, Liao Y, Hong J, Yuan Y. MicroRNA-130a is down- regulated in hepatocellular carcinoma and associates with poor prognosis. Med Oncol. 2014;31:230.

    Article  PubMed  Google Scholar 

  11. Chen P, Zhao X, Ma L. Downregulation of microRNA-100 correlates with tumor progression and poor prognosis in hepatocellular carcinoma. Mol Cell Biochem. 2013;383:49–58.

    Article  CAS  PubMed  Google Scholar 

  12. Su ZX, Zhao J, Rong ZH, Geng WM, Wu YG, Qin CK. Upregulation of microRNA-25 associates with prognosis in hepatocellular carcinoma. Diagn Pathol. 2014;9:47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Gu H, Guo X, Zou L, Zhu H, Zhang J. Upregulation of microRNA-372 associates with tumor progression and prognosis in hepatocellular carcinoma. Mol Cell Biochem. 2013;375:23–30.

    CAS  PubMed  Google Scholar 

  14. 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 

  15. Meng FL, Wang W, Jia WD. Diagnostic and prognostic significance of serum miR-24-3p in HBV-related hepatocellular carcinoma. Med Oncol. 2014;31:177.

    Article  PubMed  Google Scholar 

  16. Zhang ZQ, Meng H, Wang N, Liang LN, Liu LN, Lu SM, et al. Serum microRNA 143 and microRNA 215 as potential biomarkers for the diagnosis of chronic hepatitis and hepatocellular carcinoma. Diagn Pathol. 2014;9:135.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Koberle V, Kronenberger B, Pleli T, Trojan J, Imelmann E, Peveling-Oberhag J, et al. Serum microRNA-1 and microRNA-122 are prognostic markers in patients with hepatocellular carcinoma. Eur J Cancer. 2013;49:3442–9.

    Article  PubMed  Google Scholar 

  18. Zheng H, Liu JY, Song FJ, Chen KX. Advances in circulating microRNAs as diagnostic and prognostic markers for ovarian cancer. Cancer Biol Med. 2013;10:123–30.

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Yang Y, Gu X, Zhou M, Xiang J, Chen Z. Serum microRNAs: a new diagnostic method for colorectal cancer. Biomed Rep. 2013;1:495–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Yang MH, Yu J, Jiang DM, Li WL, Wang S, Ding YQ. microRNA-182 targets special AT-rich sequence-binding protein 2 to promote colorectal cancer proliferation and metastasis. J Transl Med. 2014;12:109.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Lei R, Tang J, Zhuang X, Deng R, Li G, Yu J, et al. Suppression of MIM by microRNA-182 activates RhoA and promotes breast cancer metastasis. Oncogene. 2014;33:1287–96.

    Article  CAS  PubMed  Google Scholar 

  22. Zhu H, Fang J, Zhang J, Zhao Z, Liu L, Wang J, et al. miR-182 targets CHL1 and controls tumor growth and invasion in papillary thyroid carcinoma. Biochem Biophys Res Commun. 2014;450:857–62.

    Article  CAS  PubMed  Google Scholar 

  23. Wang J, Li J, Shen J, Wang C, Yang L, Zhang X. MicroRNA-182 downregulates metastasis suppressor 1 and contributes to metastasis of hepatocellular carcinoma. BMC Cancer. 2012;12:227.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Qin J, Luo M, Qian H, Chen W. Upregulated miR-182 increases drug resistance in cisplatin-treated HCC cell by regulating TP53INP1. Gene. 2014;538:342–7.

    Article  CAS  PubMed  Google Scholar 

  25. Epis MR, Giles KM, Kalinowski FC, Barker A, Cohen RJ, Leedman PJ. Regulation of expression of deoxyhypusine hydroxylase (DOHH), the enzyme that catalyzes the activation of eIF5A, by miR-331-3p and miR-642-5p in prostate cancer cells. J Biol Chem. 2012;287:35251–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Guo X, Guo L, Ji J, Zhang J, Zhang J, Chen X, et al. miRNA-331-3p directly targets E2F1 and induces growth arrest in human gastric cancer. Biochem Biophys Res Commun. 2010;398:1–6.

    Article  CAS  PubMed  Google Scholar 

  27. Epis MR, Giles KM, Candy PA, Webster RJ, Leedman PJ. miR-331-3p regulates expression of neuropilin-2 in glioblastoma. J Neurooncol. 2014;116:67–75.

    Article  CAS  PubMed  Google Scholar 

  28. Chang RM, Yang H, Fang F, Xu JF, Yang LY. MicroRNA-331-3p promotes proliferation and metastasis of hepatocellular carcinoma by targeting PH domain and leucine-rich repeat protein phosphatase. Hepatology. 2014;60:1251–63.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by National Natural Science Youth Foundation of China (No. 81201351), the project of Jiangsu Provincial Commission of Health and Family Planning (No. H201453), the project of Health Bureau of Nantong city (No. WQ2014065), and the science and technology development project of Nantong City, China (Nos. HS2014061, HS2013054, and HS2011058).

Conflicts of interest

None

Author information

Authors and Affiliations

  1. Department of Gastroenterology and Clinical Laboratory, The Third People’s Hospital of Nantong City, Jiangsu, 226006, China

    Lin Chen, Yali Cao & Jianguo Shao

  2. Department of General Surgery, The Sixth People’s Hospital of Nantong City, Jiangsu, 226011, China

    Feihu Chu

  3. Department of Clinical Laboratory Center, Affiliated Hospital of Nantong University, Jiangsu, 226001, China

    Feng Wang

Authors
  1. Lin Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Feihu Chu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yali Cao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jianguo Shao
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Feng Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Jianguo Shao or Feng Wang.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chen, L., Chu, F., Cao, Y. et al. Serum miR-182 and miR-331-3p as diagnostic and prognostic markers in patients with hepatocellular carcinoma. Tumor Biol. 36, 7439–7447 (2015). https://doi.org/10.1007/s13277-015-3430-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-015-3430-2

Keywords

Search

Navigation