Skip to main content

Advertisement

Log in

Long noncoding RNAs as novel serum biomarkers for the diagnosis of hepatocellular carcinoma: a systematic review and meta-analysis

  • Research Article
  • Published:
Clinical and Translational Oncology Aims and scope Submit manuscript

Abstract

Purpose

Long noncoding RNAs (lncRNAs) are outstanding as novel cancer biomarkers with great prospects. Herein, we focused on summarizing the overall diagnostic evaluation of lncRNAs for hepatocellular carcinoma (HCC).

Methods

Relevant literature was collected from the online databases. The Quality Assessment for Studies of Diagnostic Accuracy checklist was used to assess the quality of included studies. The pooled sensitivity, specificity, and diagnostic odds ratio (DOR) were plotted using random-effects models. Summary receiver operating characteristic curve and the area under the curve (AUC) were used to estimate the overall test performance. Statistical analysis was performed by STATA 14.0 and Meta-DiSc 1.4 software.

Results

Ten studies with a total of 820 HCC patients and 785 healthy controls were included. For overall lncRNAs, the pooled sensitivity, specificity, and DOR to predict HCC patients were 80% [95% confidence interval (CI) 77–82%], 79% (95% CI 76–81%), and 27.66 (95% CI 14.26–53.63), respectively, corresponding to an AUC of 0.91.

Conclusions

LncRNAs were a high diagnostic value for HCC and its expression could potentially be used as auxiliary biomarker in confirming HCC.

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. Honeyman JN, Simon EP, Robine N, Chiaroni-Clarke R, Darcy DG, Lim II, et al. Detection of a recurrent DNAJB1-PRKACA chimeric transcript in fibrolamellar hepatocellular carcinoma. Science. 2014;343:1010–4.

    Article  CAS  Google Scholar 

  2. Anestopoulos I, Voulgaridou GP, Georgakilas AG, Franco R, Pappa A, Panayiotidis MI. Epigenetic therapy as a novel approach in hepatocellular carcinoma. Pharmacol Therapeut. 2015;145:103–19.

    Article  CAS  Google Scholar 

  3. Collins JF. Long noncoding RNAs and hepatocellular carcinoma. Gastroenterology. 2015;148:291–4.

    Article  CAS  Google Scholar 

  4. Xue M, Chen W, Li X. Urothelial cancer associated 1: A long noncoding RNA with a crucial role in cancer. J Cancer Res Clin Oncol. 2016;142:1407–19.

    Article  Google Scholar 

  5. Chang Y, Zhang K, Hu Z, Qi H, Shi Z, Han X, et al. Hypoxia-regulated lncRNAs in cancer. Gene. 2016;575:1–8.

    Article  CAS  Google Scholar 

  6. Evans JR, Feng FY, Chinnaiyan AM. The bright side of dark matter: LncRNAs in cancer. J Clin Invest. 2016;126:2775–82.

    Article  Google Scholar 

  7. Yu S, Li G, Wang Z, Wang Z, Chen C, Cai S, et al. The prognostic value of pSTAT3 in gastric cancer: a meta-analysis. J Cancer Res Clin Oncol. 2016;142:649–57.

    Article  CAS  Google Scholar 

  8. Serghiou S, Kyriakopoulou A, Ioannidis JP. Long noncoding RNAs as novel predictors of survival in human cancer: a systematic review and meta-analysis. Mol Cancer. 2016;15:50.

    Article  Google Scholar 

  9. Chen J, Chen Y, Gu L, Li X, Gao Y, Lyu X, et al. LncRNAs act as prognostic and diagnostic biomarkers in renal cell carcinoma: a systematic review and meta-analysis. Oncotarget. 2016;7(45):74325–36. doi:10.18632/oncotarget.11101.

    PubMed  PubMed Central  Google Scholar 

  10. Whiting PF, Rutjes AW, Westwood ME, Mallett S, Deeks JJ, Reitsma JB, et al. QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Ann Intern Med. 2011;155:529–36.

    Article  Google Scholar 

  11. Chu H, Guo H. A unification of models for meta-analysis of diagnostic accuracy studies. Biostatistics. 2009;10:201–3.

    Article  Google Scholar 

  12. Higgins JPT, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21:1539–58.

    Article  Google Scholar 

  13. Hao H, Chen L, Huang D, Ge J, Qiu Y, Hao L. Meta-analysis of alkaline phosphatase and prognosis for osteosarcoma. Eur J Cancer Care (Engl). 2016. doi:10.1111/ecc.12536.

    Article  Google Scholar 

  14. Deeks JJ, Macaskill P, Irwig L. The performance of tests of publication bias and other sample size effects in systematic reviews of diagnostic test accuracy was assessed. J Clin Epidemiol. 2005;58:882–93.

    Article  Google Scholar 

  15. Konishi H, Ichikawa D, Yamamoto Y, Arita T, Shoda K, Hiramoto H, et al. Plasma level of metastasis-associated lung adenocarcinoma transcript 1 is associated with liver damage and predicts development of hepatocellular carcinoma. Cancer Sci. 2016;107:149–54.

    Article  CAS  Google Scholar 

  16. Jing W, Gao S, Zhu M, Luo P, Jing X, Chai H, et al. Potential diagnostic value of lncRNA SPRY4-IT1 in hepatocellular carcinoma. Oncol Rep. 2016;36:1085–92.

    Article  CAS  Google Scholar 

  17. El-Tawdi AH, Matboli M, El-Nakeep S, Azazy AE, Abdel-Rahman O. Association of long noncoding RNA and c-JUN expression in hepatocellular carcinoma. Expert Rev Gastroenterol Hepatol. 2016;10:869–77.

    Article  CAS  Google Scholar 

  18. Kamel MM, Matboli M, Sallam M, Montasser IF, Saad AS, El-Tawdi AH. Investigation of long noncoding RNAs expression profile as potential serum biomarkers in patients with hepatocellular carcinoma. Transl Res. 2016;168:134–45.

    Article  CAS  Google Scholar 

  19. Ma W, Wang H, Jing W, Zhou F, Chang L, Hong Z, et al. Downregulation of long non-coding RNAs JPX and XIST is associated with the prognosis of hepatocellular carcinoma. Clin Res Hepatol Gastroenterol. 2016. doi:10.1016/j.clinre.2016.09.002 (In Press).

  20. Lu J, Xie F, Geng L, Shen W, Sui C, Yang J. Investigation of serum lncRNA-uc003wbd and lncRNA-AF085935 expression profile in patients with hepatocellular carcinoma and HBV. Tumour Biol. 2015;36:3231–6.

    Article  CAS  Google Scholar 

  21. Li J, Wang X, Tang J, Jiang R, Zhang W, Ji J, et al. HULC and linc00152 act as novel biomarkers in predicting diagnosis of hepatocellular carcinoma. Cell Physiol Biochem. 2015;37:687–96.

    Article  CAS  Google Scholar 

  22. Tang J, Jiang R, Deng L, Zhang X, Wang K, Sun B. Circulation long non-coding RNAs act as biomarkers for predicting tumorigenesis and metastasis in hepatocellular carcinoma. Oncotarget. 2015;6:4505–15.

    PubMed  PubMed Central  Google Scholar 

  23. Wang K, Guo WX, Li N, Gao CF, Shi J, Tang YF, et al. Serum LncRNAs profiles serve as novel potential biomarkers for the diagnosis of HBV-Positive hepatocellular carcinoma. PLoS ONE. 2015;10:e144934.

    Google Scholar 

  24. Xie H, Ma H, Zhou D. Plasma HULC as a promising novel biomarker for the detection of hepatocellular carcinoma. Biomed Res Int. 2013;2013:136106.

    PubMed  PubMed Central  Google Scholar 

  25. Aznar-Oroval E, Mancheno-Alvaro A, Garcia-Lozano T, Sanchez-Yepes M. Likelihood ratio and Fagan’s nomogram: 2 basic tools for the rational use of clinical laboratory tests. Rev Calid Asist. 2013;28:390–1.

    Article  CAS  Google Scholar 

  26. Fusar-Poli P, Cappucciati M, Rutigliano G, Heslin M, Stahl D, Brittenden Z, et al. Diagnostic stability of ICD/DSM first episode psychosis diagnoses: meta-analysis. Schizophr Bull. 2016;42:1395–406.

    Article  Google Scholar 

  27. Li CH, Chen Y. Targeting long non-coding RNAs in cancers: progress and prospects. Int J Biochem Cell Biol. 2013;45:1895–910.

    Article  CAS  Google Scholar 

  28. Esposti DD, Hernandez-Vargas H, Voegele C, Fernandez-Jimenez N, Forey N, Bancel B, et al. Identification of novel long non-coding RNAs deregulated in hepatocellular carcinoma using RNA-sequencing. Oncotarget. 2016;7:31862–77.

    Article  Google Scholar 

  29. Ouyang SS, Zhang P, Wang J, Huang ZK, Liao L. Expression of long non-coding RNA colon cancer associated transcript 2 and its clinicopathologic significance in oral squamous cell carcinoma. Zhonghua Kou Qiang Yi Xue Za Zhi. 2016;51:286–91.

    PubMed  Google Scholar 

  30. Nie F, Yu X, Huang M, Wang Y, Xie M, Ma H, et al. Long noncoding RNA ZFAS1 promotes gastric cancer cells proliferation by epigenetically repressing KLF2 and NKD2 expression. Oncotarget. 2016. doi:10.18632/oncotarget.9611.

  31. Cheng Y, Jutooru I, Chadalapaka G, Corton JC, Safe S. The long non-coding RNA HOTTIP enhances pancreatic cancer cell proliferation, survival and migration. Oncotarget. 2015;6:10840–52.

    PubMed  PubMed Central  Google Scholar 

  32. Qu S, Yang X, Song W, Sun W, Li X, Wang J, et al. Downregulation of lncRNA-ATB correlates with clinical progression and unfavorable prognosis in pancreatic cancer. Tumour Biol. 2016;37:3933–8.

    Article  CAS  Google Scholar 

  33. Zhao JH, Sun JX, Song YX, Chen XW, Yang YC, Ma B, et al. A novel long noncoding RNA-LOWEG is low expressed in gastric cancer and acts as a tumor suppressor by inhibiting cell invasion. J Cancer Res Clin Oncol. 2016;142:601–9.

    Article  CAS  Google Scholar 

  34. Chauhan R, Lahiri N. Tissue- and serum-associated biomarkers of hepatocellular carcinoma. Biomark Cancer. 2016;8:37–55.

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Wang Z, Gou W, Liu M, Sang W, Chu H, Zhang W. Expression of p53 and HSP70 in chronic hepatitis, liver cirrhosis, and early and advanced hepatocellular carcinoma tissues and their diagnostic value in hepatocellular carcinoma: an immunohistochemical study. Med Sci Monit. 2015;21:3209–15.

    Article  CAS  Google Scholar 

  36. Kudo M, Izumi N, Sakamoto M, Matsuyama Y, Ichida T, Nakashima O, et al. Survival analysis over 28 years of 173,378 patients with hepatocellular carcinoma in Japan. Liver Cancer. 2016;5:190–7.

    Article  Google Scholar 

  37. Li Z, You K, Li J, Wang Y, Xu H, Gao B, et al. Madecassoside suppresses proliferation and invasiveness of HGF-induced human hepatocellular carcinoma cells via PKC-cMET-ERK1/2-COX-2-PGE2 pathway. Int Immunopharmacol. 2016;33:24–32.

    Article  CAS  Google Scholar 

  38. Smekalova EM, Kotelevtsev YV, Leboeuf D, Shcherbinina EY, Fefilova AS, Zatsepin TS, et al. LncRNA in the liver: prospects for fundamental research and therapy by RNA interference. Biochimie. 2016;131:159–72.

    Article  CAS  Google Scholar 

  39. Parasramka MA, Maji S, Matsuda A, Yan IK, Patel T. Long non-coding RNAs as novel targets for therapy in hepatocellular carcinoma. Pharmacol Ther. 2016;161:67–78.

    Article  CAS  Google Scholar 

  40. Cui Z, Chen Y, Xiao Z, Hu M, Lin Y, Chen Y, et al. Long noncoding RNAs as auxiliary biomarkers for gastric cancer screening: a pooled analysis of individual studies. Oncotarget. 2016;7:25791–800.

    PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We thank Elsevier’s English Language Editing service for editing the manuscript. This work was supported by grants from the National Natural Science Foundation of China (81560475).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to J. Shao.

Ethics declarations

Conflict of interest

The authors have no conflicts to disclose.

Additional information

C. Zheng and H. Hao equally contributed to this work.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zheng, C., Hao, H., Chen, L. et al. Long noncoding RNAs as novel serum biomarkers for the diagnosis of hepatocellular carcinoma: a systematic review and meta-analysis. Clin Transl Oncol 19, 961–968 (2017). https://doi.org/10.1007/s12094-017-1626-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12094-017-1626-1

Keywords

Navigation