Neoplasma. 2016;63(2):223-30. doi: 10.4149/207_150821N454.
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 H19 has been reported to be upregulated in diverse human cancers; however, its clinical significance in gastric cancer (GC) remains elusive. Expression levels of H19 in 128 pairs of GC and adjacent normal tissues, GC cell lines and GC juices compared to their corresponding controls were detected by real-time quantitative polymerase chain reaction (qPCR) 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. H19 expression was remarkably increased in GC 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 GC. H19 levels were robust in differentiating GC tissues from controls [area under the curve (AUC) = 0.697; 95% confidence interval (CI) = 0.636-0.752, p<0.01]. Kaplan-Meier analysis demonstrated that increased H19 expression contributed to poor overall survival (P = 0.017) and disease-free survival (P = 0.024) of patients. A multivariate survival analysis also indicated that H19 could be an independent prognostic marker. The levels of H19 in gastric juice from gastric patients were significantly higher than those from normal subjects (P = 0.034). Furthermore, knockdown of H19 expression by siRNA could inhibit cell migration and invasion in GC cells partly via regulating E-cadherin protein expression. H19 might serve as a promising biomarker for early detection and prognosis prediction of GC.
越来越多的证据表明,失调的长非编码 RNA(lncRNA)参与了癌症的发生和发展,可能被用作诊断和预后的生物标志物,或潜在的治疗靶点。已有报道称,lncRNA H19 在多种人类癌症中上调;然而,其在胃癌(GC)中的临床意义仍不清楚。通过实时定量聚合酶链反应(qPCR)检测 128 对 GC 及相邻正常组织、GC 细胞系和 GC 汁与相应对照中 H19 的表达水平。通过构建受试者工作特征(ROC)曲线和 Kaplan-Meier 分析来评估诊断和预后价值。使用 Cox 比例风险分析进行单变量和多变量分析。与正常对照组相比,GC 组织和细胞系中 H19 的表达明显升高,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。H19 水平在区分 GC 组织与对照组方面具有很强的稳健性[AUC=0.697;95%置信区间(CI)=0.636-0.752,p<0.01]。Kaplan-Meier 分析表明,H19 表达增加与患者总生存期(P=0.017)和无病生存期(P=0.024)较差相关。多变量生存分析也表明 H19 可以作为独立的预后标志物。胃癌患者胃液中的 H19 水平明显高于正常受试者(P=0.034)。此外,通过 siRNA 敲低 H19 表达可部分通过调节 E-钙黏蛋白蛋白表达抑制 GC 细胞的迁移和侵袭。H19 可能成为 GC 早期检测和预后预测的有前途的生物标志物。