Aberrant expression of long noncoding RNA PVT1 and its diagnostic and prognostic significance in patients with gastric cancer

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.