Circulating long noncoding RNA GAS5 is a novel biomarker for the diagnosis of nonsmall cell lung cancer.
Circulating long noncoding RNA GAS5 is a novel biomarker for the diagnosis of nonsmall cell lung cancer.
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循环长链非编码RNA GAS5是诊断非小细胞肺癌的新型生物标志物
DOI：
10.1097/md.0000000000004608
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发表时间：
2016-09
期刊：
影响因子：
1.6
通讯作者：
Song Y
中科院分区：
文献类型：
--
作者：
Liang W;Lv T;Shi X;Liu H;Zhu Q;Zeng J;Yang W;Yin J;Song Y
摘要近年来发现的长链非编码RNA具有调节多种生物学过程的潜力，在多种肿瘤中表达异常。我们前期的研究表明，肺癌组织中长链非编码RNA生长抑制特异性转录本5（GAS 5）表达减少，这与非小细胞肺癌（NSCLC）的增殖和凋亡有关。GAS 5与肺癌患者的预后有关。这些结果表明，GAS 5可能代表一种新的预后指标和基因治疗NSCLC的目标。然而，GAS 5在NSCLC患者血浆中的表达及其诊断意义尚不清楚。由于临床上血浆样本比组织样本更容易获得，因此我们设计了这项研究来探讨血液样本中GAS 5的诊断价值。在我们的研究中，90例NSCLC患者和33例健康对照者被纳入。在手术和治疗前收集血液样本。提取血浆中游离RNA，采用定量逆转录PCR方法分析GAS 5的表达。采用适当的统计学方法比较NSCLC患者和健康对照者术前、术后血浆GAS 5水平。采用受试者工作特征曲线分析评价血浆GAS 5对NSCLC诊断的敏感性和特异性。结果表明，GAS 5在NSCLC患者血浆中可检测到且稳定。此外，与健康对照组相比，NSCLC患者的血浆GAS 5水平显著下调（P = 0.000）。 此外，NSCLC患者术后第7天的GAS 5水平较术前显著升高（P = 0.003）。 GAS 5表达水平可用于区分NSCLC患者和对照患者，曲线下面积为0.832（P <0.0001;敏感性，82.2%;特异性，72.7%）。 GAS 5和癌胚抗原联合检测可产生0.909的受试者工作特征曲线下面积，用于区分NSCLC患者和对照受试者（95%置信区间0.857-0.962，P = 0.000）。 我们已经证明GAS 5表达在NSCLC血浆中降低。临床上血浆样本比组织样本更容易获得，因此GAS 5可能是诊断NSCLC的理想生物标志物。
Abstract The recently discovered long noncoding RNAs have the potential to regulate many biological processes, which are aberrantly expressed in many tumor types. Our previous study showed that the long noncoding RNA-growth arrest-specific transcript 5 (GAS5) was decreased in lung cancer tissue, which contributed to the proliferation and apoptosis of nonsmall cell lung cancer (NSCLC). GAS5 was also associated with the prognosis of lung cancer patients. These results suggest that GAS5 may represent a novel prognostic indicator and a target for gene therapy in NSCLC. However, the expression and diagnosis significance of GAS5 in the plasma of NSCLC patients was unknown. The plasma samples were more readily available than the tissue samples in clinical, so we designed the study to investigate the diagnosis value of GAS5 in blood samples. In our study, 90 patients with NSCLC and 33 healthy controls were included. Blood samples were collected before surgery and therapy. We extracted the free RNA in the plasma and analyzed the expression of GAS5 with quantitative reverse transcription PCR. Suitable statistics methods were used to compare the plasma GAS5 levels of preoperative and postoperative plasma samples between the NSCLC patients and healthy controls. Receiver-operating characteristic curve analysis was used to evaluate the diagnostic sensitivity and specificity of plasma GAS5 in NSCLC. The results showed that GAS5 was detectable and stable in the plasma of NSCLC patients. Furthermore, the plasma levels of GAS5 were significantly down-regulated in NSCLC patients compared with healthy controls (P = 0.000). Moreover, GAS5 levels increased markedly on the seventh day after surgery compared with preoperative GAS5 levels in NSCLC patients (P = 0.003). GAS5 expression levels could be used to distinguish NSCLC patients from control patients with an area under the curve of 0.832 (P < 0.0001; sensitivity, 82.2%; specificity, 72.7%). The combination of the GAS5 and carcinoembryonic antigen could produce an area of 0.909 under the receiver-operating characteristic curve in distinguishing NSCLC patients from control subjects (95% confidence interval 0.857–0.962, P = 0.000). We have demonstrated that GAS5 expression was decreased in NSCLC Plasma. Plasma samples were more accessible than tissue samples in clinical; therefore, GAS5 could be an ideal biomarker for the diagnosis of NSCLC.