Tumor Biology

, Volume 36, Issue 5, pp 3231–3236 | Cite as

Investigation of serum lncRNA-uc003wbd and lncRNA-AF085935 expression profile in patients with hepatocellular carcinoma and HBV

  • Jiongjiong Lu
  • Feng Xie
  • Li Geng
  • Weifeng Shen
  • Chengjun Sui
  • Jiamei Yang
Research Article


Hepatocellular carcinoma (HCC) was among the most common solid tumors which rated third in cancer-related mortality worldwide. Hepatitis B viral (HBV) infection represents an important risk factor for HCC. Long non-coding RNAs (lncRNAs) were a class of newfound non-coding RNAs widely depicted in the genome currently. Nevertheless, the potential roles of them in human cancers were not well comprehended. Through this study, we aimed at exploring the expression profile and the potential clinical value of two lncRNAs (lncRNA-uc003wbd and lncRNA-AF085935) in differentiating HCC from both HBV patients and the healthy specimens. Serum samples were extracted from 104 HBV patients, 137 HCC patients, and 138 healthy controls. The lncRNA levels of all the subjects were assayed by quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR). We differentiated the three groups by the receiver operating characteristic (ROC) curve of each group. Statistical analyses were conducted by GraphPad software. Two-tailed P value less than 0.05 was considered to be statistically significant. The level of serum lncRNA-uc003wbd and lncRNA-AF085935 was significantly upregulated in HCC patients and HBV patients compared with that in normal controls. LncRNA-AF085935 showed a relatively higher accuracy for HCC screening (area under the curve (AUC) = 0.96, 95 % confidence interval (CI) = 0.93–0.99) than lncRNA-uc003wbd (AUC = 0.86, 95 % CI = 0.82–0.91) from healthy controls, as well as for HCC screening (AUC = 0.86, 95 % CI = 0.80–0.91) which is more accurate than lncRNA-uc003wbd (AUC = 0.70, 95 % CI = 0.63–0.76) from HBV patients. When differentiating HBV patients from the normal group, the descriptive value of lncRNA-AF085935 (AUC = 0.77, 95 % CI = 0.71–0.83) was almost as equal to lncRNA-uc003wbd (AUC = 0.76, 95 % CI = 0.70–0.82). In addition, higher expressions of lncRNAs were observed in HCC patients than in HBV patients. LncRNA-uc003wbd and lncRNA-AF085935 were observed with an aberrant serum level in HCC and HBV patients, which is showing that both lncRNA-uc003wbd and lncRNA-AF085935 are able to be potential biomarkers for HCC and HBV screening.


Long non-coding RNA Serum Hepatocellular carcinoma HBV Screening 


Conflicts of interest



  1. 1.
    Bihrer V, Waidmann O, Friedrich-Rust M, Forestier N, Susser S, Haupenthal J, et al. Serum microRNA-21 as marker for necroinflammation in hepatitis C patients with and without hepatocellular carcinoma. PLoS One. 2011;6:e26971. doi: 10.1371/journal.pone.0026971.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Tomimaru Y, Eguchi H, Nagano H, Wada H, Kobayashi S, Marubashi S, et al. Circulating microRNA-21 as a novel biomarker for hepatocellular carcinoma. J Hepatol. 2012;56:167–75. doi: 10.1016/j.jhep.2011.04.026.CrossRefPubMedGoogle Scholar
  3. 3.
    Zhao Q, Li T, Qi J, Liu J, Qin C. The miR-545/374a cluster encoded in the Ftx lncRNA is overexpressed in HBV-related hepatocellular carcinoma and promotes tumorigenesis and tumor progression. PLoS One. 2014;9:e109782. doi: 10.1371/journal.pone.0109782.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Abdalla MA, Haj-Ahmad Y. Promising candidate urinary MicroRNA biomarkers for the early detection of hepatocellular carcinoma among high-risk hepatitis C virus Egyptian patients. J Cancer Educ. 2012;3:19–31.CrossRefGoogle Scholar
  5. 5.
    Qu KZ, Zhang K, Li H, Afdhal NH, Albitar M. Circulating microRNAs as biomarkers for hepatocellular carcinoma. J Clin Gastroenterol. 2011;45:355–60. doi: 10.1097/MCG.0b013e3181f18ac2.CrossRefPubMedGoogle Scholar
  6. 6.
    Zhao Y, Guo Q, Chen J, Hu J, Wang S, Sun Y. Role of long non-coding RNA HULC in cell proliferation, apoptosis and tumor metastasis of gastric cancer: a clinical and in vitro investigation. Oncol Rep. 2014;31:358–64. doi: 10.3892/or.2013.2850.PubMedGoogle Scholar
  7. 7.
    Amaral PP, Clark MB, Gascoigne DK, Dinger ME, Mattick JS. lncRNAdb: a reference database for long noncoding RNAs. Nucleic Acids Res. 2011;39:D146–51. doi: 10.1093/nar/gkq1138.CrossRefPubMedGoogle Scholar
  8. 8.
    Volders PJ, Helsens K, Wang X, Menten B, Martens L, Gevaert K, et al. LNCipedia: a database for annotated human lncRNA transcript sequences and structures. Nucleic Acids Res. 2013;41:D246–51. doi: 10.1093/nar/gks915.CrossRefPubMedGoogle Scholar
  9. 9.
    Lai MC, Yang Z, Zhou L, Zhu QQ, Xie HY, Zhang F, et al. Long non-coding RNA MALAT-1 overexpression predicts tumor recurrence of hepatocellular carcinoma after liver transplantation. Med Oncol. 2012;29:1810–6. doi: 10.1007/s12032-011-0004-z.CrossRefPubMedGoogle Scholar
  10. 10.
    Sun J, Shi H, Wang Z, Zhang C, Liu L, Wang L, et al. Inferring novel lncRNA-disease associations based on a random walk model of a lncRNA functional similarity network. Mol Biosyst. 2014;10:2074–81. doi: 10.1039/c3mb70608g.CrossRefPubMedGoogle Scholar
  11. 11.
    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. doi: 10.1007/s13277-014-2259-4.Google Scholar
  12. 12.
    Zhang W, Huang C, Gong Z, Zhao Y, Tang K, Li X, et al. Expression of LINC00312, a long intergenic non-coding RNA, is negatively correlated with tumor size but positively correlated with lymph node metastasis in nasopharyngeal carcinoma. J Mol Histol. 2013;44:545–54. doi: 10.1007/s10735-013-9503-x.CrossRefPubMedGoogle Scholar
  13. 13.
    Weber DG, Johnen G, Casjens S, Bryk O, Pesch B, Jockel KH, et al. Evaluation of long noncoding RNA MALAT1 as a candidate blood-based biomarker for the diagnosis of non-small cell lung cancer. BMC Res Notes. 2013;6:518. doi: 10.1186/1756-0500-6-518.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    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. doi: 10.1371/journal.pone.0000845.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Matouk IJ, Abbasi I, Hochberg A, Galun E, Dweik H, Akkawi M. Highly upregulated in liver cancer noncoding RNA is overexpressed in hepatic colorectal metastasis. Eur J Gastroenterol Hepatol. 2009;21:688–92.CrossRefPubMedGoogle Scholar
  16. 16.
    Hao K, Luk JM, Lee NP, Mao M, Zhang C, Ferguson MD, et al. Predicting prognosis in hepatocellular carcinoma after curative surgery with common clinicopathologic parameters. BMC Cancer. 2009;9:389. doi: 10.1186/1471-2407-9-389.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Hou J, Lin L, Zhou W, Wang Z, Ding G, Dong Q, et al. Identification of miRNomes in human liver and hepatocellular carcinoma reveals miR-199a/b-3p as therapeutic target for hepatocellular carcinoma. Cancer Cell. 2011;19:232–43. doi: 10.1016/j.ccr.2011.01.001.CrossRefPubMedGoogle Scholar
  18. 18.
    Wang J, Liu X, Wu H, Ni P, Gu Z, Qiao Y, et al. CREB up-regulates long non-coding RNA, HULC expression through interaction with microRNA-372 in liver cancer. Nucleic Acids Res. 2010;38:5366–83. doi: 10.1093/nar/gkq285.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Yang F, Xue X, Bi J, Zheng L, Zhi K, Gu Y, et al. Long noncoding RNA CCAT1, which could be activated by c-Myc, promotes the progression of gastric carcinoma. J Cancer Res Clin Oncol. 2013;139:437–45. doi: 10.1007/s00432-012-1324-x.CrossRefPubMedGoogle Scholar
  20. 20.
    Pickard MR, Mourtada-Maarabouni M, Williams GT. Long non-coding RNA GAS5 regulates apoptosis in prostate cancer cell lines. Biochim Biophys Acta. 1832;2013:1613–23. doi: 10.1016/j.bbadis.2013.05.005.Google Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Jiongjiong Lu
    • 1
  • Feng Xie
    • 1
  • Li Geng
    • 1
  • Weifeng Shen
    • 1
  • Chengjun Sui
    • 1
  • Jiamei Yang
    • 1
  1. 1.The Department of Special Treatment, Eastern Hepatobiliary Surgery HospitalSecond Military Medical UniversityShanghaiChina

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