Serum LncRNAs Profiles Serve as Novel Potential Biomarkers for the Diagnosis of HBV-Positive Hepatocellular Carcinoma

PLoS One. 2015 Dec 16;10(12):e0144934. doi: 10.1371/journal.pone.0144934. eCollection 2015.

Abstract

Background: Hepatocellular carcinoma (HCC) is a common malignancy that has a poor prognosis because there is lack of methods for early diagnosis. We aimed to utilize two serum long non-coding RNAs (lncRNAs), uc001ncr and AX800134, to diagnose hepatitis B virus (HBV)-positive HCC.

Methods: lncRNA microarrays were utilized to measure the differential expression of lncRNAs between tumor tissues and corresponding non-tumor tissues in HBV-positive hapatocellular carcinoma. uc001ncr and AX800134 were selected as candidate lncRNAs and detected in three independent cohorts containing a total of 684 participants (healthy individuals and chronic HBV patients and HBV-positive HCC patients) who were recruited between March 2011 and December 2012. A logistic regression model was constructed using a training cohort (n = 353) and validated using an independent cohort (n = 181). The area under the receiver operating characteristic curve (AUC) was utilized to evaluate the diagnostic accuracy.

Results: We determined that a panel based on the expression of uc001ncr and AX800134 accurately diagnosed HBV-positive HCC (AUC values of 0.9494 and 0.9491 for the training and validation cohorts, respectively). The diagnostic performance of the panel remained high in patients with AFP≤400 ng/ml (AUC values of 0.9371 and 0.9527 for the training and validation cohorts, respectively). The panel also diagnosed early HCC (AUC values of 0.9450 and 0.9564 for the training and validation cohorts, respectively).

Conclusion: Our results indicated that the serum expression of uc001ncr and AX800134 has potential as novel potential biomarker for the diagnosis of HCC, especially in patients with AFP≤400 ng/ml or early-stage disease (BCLC 0+A).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor
  • Carcinoma, Hepatocellular / diagnosis*
  • Carcinoma, Hepatocellular / etiology*
  • Case-Control Studies
  • Cluster Analysis
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Hepatitis B, Chronic / complications*
  • Humans
  • Liver Neoplasms / diagnosis*
  • Liver Neoplasms / etiology*
  • Male
  • Prognosis
  • RNA, Long Noncoding / blood
  • RNA, Long Noncoding / genetics*
  • ROC Curve
  • Reproducibility of Results
  • Transcriptome*

Substances

  • Biomarkers, Tumor
  • RNA, Long Noncoding

Grants and funding

This work was supported by the grants of the Science Fund for Creative Research Groups (No. 81221061); Chang Jiang Scholars Program (2012); Shanghai Science and Technology Committee (No. 134119a0200); The State Key Project on Infections Diseases of China (2012zx10002016016003); The China National Funds for Distinguished Young Scientists (No. 81125018); The New Excellent Talents Program of Shanghai Municipal Health Bureau (No. XBR2011025); The New Excellent Talents Program of Shanghai Science and Technology Committee (No. 10XD1405800); Shanghai Science and Technology Committee (No. 10JC1417600); The National Natural Science Foundation (No. 81101831); Excellent Young Scholar Program of SMMU (No. 20111010B); and Project supported by the Natural Science Foundation of Shanghai, China (No. 12ZR1439600).