Abstract
Accumulating evidence indicates that long non-coding RNAs (lncRNAs) play important roles in tumorigenesis and progression. We aimed to identify a panel of lncRNAs for the diagnosis and recurrence prediction in bladder cancer (BC). The expression of 13 candidate lncRNAs was investigated in 80 BC and matched adjacent normal tissues via quantitative real-time PCR. The differentially expressed lncRNAs were then analyzed in 240 serum samples (training set) and three lncRNAs (MEG3, SNHG16 and MALAT1) showed differential expression. A logistic regression model was constructed using the training set and validated in an independent cohort of 200 serum samples (validation set). The AUC of the three-lncRNA panel was 0.865 for the training and 0.828 for the validation set. The diagnostic performance of the lncRNA panel for Ta, T1, and T2–T4 were 0.778, 0.805, and 0.880, which were significantly higher than those of urine cytology (0.548, 0.604, and 0.682, respectively). Moreover, we determined that low expression of MEG3 was associated with poor recurrence-free survival by Kaplan-Meier analysis (p = 0.028), univariate Cox analysis (p = 0.033) and multivariate Cox analysis (p = 0.046). In conclusion, our results identified a three-lncRNA panel for BC diagnosis and a recurrence-independent prognostic factor, MEG3.
Highlights
Bladder cancer (BC) is one of the most common urogenital malignancies worldwide, and is characterized by a high recurrence rate [1, 2]
The relative expression levels of 13 long non-coding RNAs (lncRNAs) were measured by quantitative real-time PCR (qRT-PCR) in 80 bladder cancer (BC) samples and matched adjacent normal tissues
The nonparametric Mann-Whitney U tests for the identification revealed that 11 of 13 lncRNAs were significantly dys-regulated between bladder samples and matched adjacent normal tissues
Summary
Bladder cancer (BC) is one of the most common urogenital malignancies worldwide, and is characterized by a high recurrence rate [1, 2]. Screening and monitoring are essential for early and improved treatment of BC. Cystoscopy and cytology are currently the standard modalities used to diagnose and monitor urothelial carcinoma. Cystoscopy is invasive, costly and often associated with discomfort; voided urine cytology lacks the diagnostic sensitivity necessary to rule out cancer. More reliable non-invasive makers of bladder cancer are urgently needed. Many urine-based biomarkers, such as bladder tumor antigen (BTA), nuclear matrix protein 22 (NMP22) and cytokeratin, have been developed during the past decades, but all of them have lower specificity than cytology, and none of them is recommended for large-scale cancer screening [3]
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