H19 serves as a diagnostic biomarker and up-regulation of H19 expression contributes to poor prognosis in patients with gastric cancer

Abstract

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 H19in 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. H19expression 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. H19levels 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 H19expression contributed to poor overall survival (P= 0.017) and disease-free survival (P= 0.024) of patients. A multivariate survival analysis also indicated that H19could be an independent prognostic marker. The levels of H19in gastric juice from gastric patients were significantly higher than those from normal subjects (P= 0.034). Furthermore, knockdown of H19expression by siRNA could inhibit cell migration and invasion in GC cells partly via regulating E-cadherin protein expression. H19might serve as a promising biomarker for early detection and prognosis prediction of GC.