Abstract
Exosomes are small membrane vesicles released by many cells. These vesicles can mediate cellular communications by transmitting active molecules including long non‐coding RNAs (lncRNAs). In this study, our aim was to identify a panel of lncRNAs in serum exosomes for the diagnosis and recurrence prediction of bladder cancer (BC). The expressions of 11 candidate lncRNAs in exosome were investigated in training set (n = 200) and an independent validation set (n = 320) via quantitative real‐time PCR. A three‐lncRNA panel (PCAT‐1, UBC1 and SNHG16) was finally identified by multivariate logistic regression model to provide high diagnostic accuracy for BC with an area under the receiver‐operating characteristic curve (AUC) of 0.857 and 0.826 in training set and validation set, respectively, which was significantly higher than that of urine cytology. The corresponding AUCs of this panel for patients with Ta, T1 and T2‐T4 were 0.760, 0.827 and 0.878, respectively. In addition, Kaplan‐Meier analysis showed that non‐muscle‐invasive BC (NMIBC) patients with high UBC1 expression had significantly lower recurrence‐free survival (P = 0.01). Multivariate Cox analysis demonstrated that UBC1 was independently associated with tumour recurrence of NMIBC (P = 0.018). Our study suggested that lncRNAs in serum exosomes may serve as considerable diagnostic and prognostic biomarkers of BC.
Highlights
Bladder cancer (BC) is the most common carcinoma of the urinary tract, and there are approximately 80 500 new cases and 32 900 BC‐related deaths in China in 2015.1,2 Around 70% of BC patients are diagnosed as a non‐muscle‐invasive BC (NMIBC) characterized by a high recurrence rate, while the remaining 30% were diagnosed as a muscle‐invasive BC (MIBC) with poor prognosis.[3]
We identified three up‐regulated serum exosomal Long non‐coding RNAs (lncRNAs) (PCAT‐1, UBC1 and SNHG16) in BC and further
LncRNAs can be protected by exosomes from degradation in the circulation, and they are useful for cancer diagnosis at the early stage.[37]
Summary
Bladder cancer (BC) is the most common carcinoma of the urinary tract, and there are approximately 80 500 new cases and 32 900 BC‐related deaths in China in 2015.1,2 Around 70% of BC patients are diagnosed as a non‐muscle‐invasive BC (NMIBC) characterized by a high recurrence rate, while the remaining 30% were diagnosed as a muscle‐invasive BC (MIBC) with poor prognosis.[3]. Long non‐coding RNAs (lncRNAs) are a class of transcripts longer than 200 nucleotides with limited protein coding potential.[7,8] Accumulating evidences show that lncRNAs are involved in tumour initiation and progression through regulating associated gene expressions at the transcriptional,[9,10] posttranscriptional,[11,12] or epigenetic levels.[13,14] The aberrant lncRNAs have been reported as potential markers for diagnosis and prognosis of cancers. Increased expression of ZEB1‐AS1 promotes tumour metastasis and predicts poor prognosis in hepatocellular carcinoma,[15] while overexpression of CRNDE‐h has been proposed as a potential novel molecular marker for colorectal cancer.[16] These studies indicate that lncRNAs can serve as minimally invasive biomarkers of diagnosis and prognosis in different tumours
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