长链非编码 RNA PVT1 在胃癌患者中的异常表达及其诊断和预后意义。
Aberrant expression of long noncoding RNA PVT1 and its diagnostic and prognostic significance in patients with gastric cancer.
出版信息
Neoplasma. 2016;63(3):442-9. doi: 10.4149/314_150825N45.
Emerging evidences indicate that dysregulated long noncoding RNAs (lncRNAs) are implicated in cancer tumorigenesis and progression and might be used as diagnosis and prognosis biomarker, or potential therapeutic targets. LncRNA PVT1 has been reported to be upregulated in diverse human cancers; however, its clinical significance in gastric cancer (GC) remains elusive. This study was to evaluate the expression of PVT1 in GC and further explore its clinical significance.Previous microarray datasets were analyzed to conduct a preliminary screening for candidate lncRNAs of gastric cancer biomarkers in human gastric cancer tissues. Expression levels of PVT1 in 111pairs of gastric cancer and adjacent normal tissues, gastric cancer cell lines and gastric cancer juices compared to their corresponding controls were detected by real-time quantitative RT-PCR assay. A receiver operating characteristic (ROC) curve and Kaplan-Meier analysis were constructed to evaluate the diagnostic and prognostic values. Univariate and multivariate analysis were performed using the Cox proportional hazard analysis.PVT1 expression was remarkably increased in gastric cancer tissues and cell lines compared with that in the normal control, and its up-regulation was significantly correlated to invasion depth (P < 0.001), advanced TNM stage (P = 0.002) and regional lymph nodes metastasis (P < 0.001) in gastric cancer. PVT1 levels were robust in differentiating gastric cancer tissues from controls [area under the curve (AUC) = 0.728; 95 % confidence interval (CI) = 0.665-0.786, p<0.01]. Kaplan-Meier analysis demonstrated that increased PVT1 expression contributed to poor overall survival (P < 0.01) and disease-free survival (P < 0.01) of patients. A multivariate survival analysis also indicated that PVT1 could be an independent prognostic marker. The levels of PVT1 in gastric juice from gastric patients were significantly higher than those from normal subjects (P = 0.03). PVT1 might serve as a promising biomarker for early detection and prognosis prediction of gastric cancer.
新兴证据表明，失调的长非编码 RNA（lncRNA）参与癌症的发生和进展，可作为诊断和预后的生物标志物，或作为潜在的治疗靶点。已有研究报道，多种人类癌症中 PVT1 呈上调表达；然而，其在胃癌（GC）中的临床意义仍不清楚。本研究旨在评估 PVT1 在 GC 中的表达，并进一步探讨其临床意义。分析了之前的微阵列数据集，以对人类胃癌组织中胃癌生物标志物的候选 lncRNA 进行初步筛选。通过实时定量 RT-PCR 检测 111 对胃癌及癌旁正常组织、胃癌细胞系和胃癌胃液与相应对照中 PVT1 的表达水平。构建受试者工作特征（ROC）曲线和 Kaplan-Meier 分析以评估诊断和预后价值。使用 Cox 比例风险分析进行单因素和多因素分析。PVT1 在胃癌组织和细胞系中的表达明显高于正常对照，其上调与浸润深度（P<0.001）、晚期 TNM 分期（P=0.002）和区域淋巴结转移（P<0.001）显著相关。PVT1 水平在区分胃癌组织与对照组方面具有很好的区分能力[曲线下面积（AUC）=0.728；95%置信区间（CI）=0.665-0.786，p<0.01]。Kaplan-Meier 分析表明，PVT1 表达增加与患者总生存（P<0.01）和无病生存（P<0.01）不良相关。多因素生存分析也表明，PVT1 可以作为独立的预后标志物。胃癌患者胃液中的 PVT1 水平明显高于正常对照者（P=0.03）。PVT1 可能成为早期检测和预测胃癌预后的有前途的生物标志物。
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