下调长链非编码 RNA GAS5-AS1 及其在肝细胞癌中的预后和诊断意义。

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

机构信息

Department of Clinical Laboratory Medicine and Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University, Wuhan 430071, Hubei, China.

Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Key laboratory of Laboratory Medicine of Henan, Zhengzhou 450000, China.

出版信息

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

DOI:10.3233/CBM-170781

PMID:29660898

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.

摘要

背景

肝细胞癌（HCC）是全球范围内最常见的实体肿瘤，具有高度恶性和预后不良的特点。但 GAS5-AS1 的表达与 HCC 之间的关系尚未有文献记载。本研究旨在分析 GAS5-AS1 的表达谱，并探讨其在 HCC 中的临床意义。

方法

采用实时定量 PCR（RT-qPCR）检测 83 对 HCC 手术组织和相邻正常肝组织中 GAS5-AS1 的表达。我们还对 156 例 HCC 患者和 58 例健康对照者的血浆样本进行了 RT-qPCR 检测。

结果

我们发现 GAS5-AS1 在 HCC 组织中表达下调（P<0.01）。相关性分析显示，GAS5-AS1 的表达与分化程度（高/中 vs 低，P=0.031）、肿瘤-淋巴结-转移（TNM）分期（I∼II 期 vs III∼IV 期，P=0.020）和血糖水平（<6.2 vs≧6.2，P=0.047）显著相关。总生存分析显示，GAS5-AS1 低表达的患者预后相对较差。单因素和多因素分析表明，GAS5-AS1 是 HCC 患者的独立预后因素。ROC 曲线下面积（AUCROC）表明，GAS5-AS1 对 HCC 的诊断具有较高的准确性（AUC=0.824，95%CI：0.741-0.906）。当区分 AFP<200ng/ml 的 HCC 病例与 AFP 水平也低于 200ng/ml 的肝硬化和乙型肝炎时，GAS5-AS1 具有较高的敏感性（分别为 89.5%、89.5%）。