Down-regulation of long non-coding RNA GAS5-AS1 and its prognostic and diagnostic significance in hepatocellular carcinoma

Cancer Biomark. 2018;22(2):227-236. doi: 10.3233/CBM-170781.

Abstract

Background: Hepatocellular carcinoma (HCC) is the most common solid tumor in global range, with high degree of malignancy and poor prognosis. But the relationship between the expression of GAS5-AS1 and HCC is not documented. This study aimed to profile GAS5-AS1 expression signature and then to explore its clinical significance in HCC.

Methods: Quantitative real-time PCR (RT-qPCR) was performed to detect the expression of GAS5-AS1 in 83 pairs of HCC surgical tissues and adjacent normal liver tissues. We also performed RT-qPCR on plasma samples of 156 patients and 58 healthy controls.

Results: We found that GAS5-AS1 was down-regulated in HCC tissues (P< 0.01). Correlation analysis showed that the expression of GAS5-AS1 was notably associated with differentiation (High/Moderate vs Low, P= 0.031), tumor-node-metastasis (TNM) stage (I∼II vs III∼IV, P= 0.020) and glucose levels (< 6.2 vs≧ 6.2, P= 0.047) in HCC patients. The overall survival analysis showed that patients with lower GAS5-AS1 expression had a relatively poor prognosis. Univariate and multivariate analysis elaborated that GAS5-AS1 was an independent prognostic factor for HCC patients. The area under the ROC (AUCROC) demonstrated that GAS5-AS1 presented a high accuracy (AUC = 0.824, 95% CI: 0.741-0.906) for distinguishing HCC from the cirrhosis. When differentiating HCC cases with AFP < 200 ng/ml from the cirrhosis and hepatitis B whose AFP levels were also below 200 ng/ml, GAS5-AS1 had the high sensitivity (89.5%, 89.5%, respectively).

Conclusions: GAS5-AS1 could be considered as a potential prognostic and diagnostic marker in HCC. However, the potential clinical application value of GAS5-AS1 still needs to be further illustrated.

Keywords: GAS5-AS1; Hepatocellular carcinoma; diagnosis; long non-coding RNA; prognosis.

MeSH terms

  • Adult
  • Aged
  • Biomarkers
  • Biomarkers, Tumor*
  • Carcinoma, Hepatocellular / diagnosis*
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / mortality
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Kaplan-Meier Estimate
  • Liver Cirrhosis / complications
  • Liver Cirrhosis / pathology
  • Liver Neoplasms / diagnosis*
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / mortality
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • RNA, Antisense / genetics*
  • RNA, Long Noncoding / genetics*
  • ROC Curve

Substances

  • Biomarkers
  • Biomarkers, Tumor
  • GAS5 long non-coding RNA, human
  • RNA, Antisense
  • RNA, Long Noncoding