Expression signatures of exosomal long non-coding RNAs in urine serve as novel non-invasive biomarkers for diagnosis and recurrence prediction of bladder cancer

Abstract

Recently, expression signatures of exosomal long non-coding RNAs (lncRNAs) have been proposed as potential non-invasive biomarkers for cancer detection. In this study, we aimed to develop a urinary exosome (UE)-derived lncRNA panel for diagnosis and recurrence prediction of bladder cancer (BC). Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to screen and evaluate the expressions of eight candidate lncRNAs in a training set (208 urine samples) and a validation set (160 urine samples). A panel consisting of three differently expressed lncRNAs (MALAT1, PCAT-1 and SPRY4-IT1) was established for BC diagnosis in the training set, showing an area under the receiver-operating characteristic (ROC) curve (AUC) of 0.854. Subsequently, the performance of the panel was further verified with an AUC of 0.813 in the validation set, which was significantly higher than that of urine cytology (0.619). In addition, Kaplan-Meier analysis suggested that the up-regulation of PCAT-1 and MALAT1 was associated with poor recurrence-free survival (RFS) of non-muscle-invasive BC (NMIBC) (p < 0.001 and p = 0.002, respectively), and multivariate Cox proportional hazards regression analysis revealed that exosomal PCAT-1 overexpression was an independent prognostic factor for the RFS of NMIBC (p = 0.018). Collectively, our findings indicated that UE-derived lncRNAs possessed considerable clinical value in the diagnosis and prognosis of BC.Electronic supplementary materialThe online version of this article (10.1186/s12943-018-0893-y) contains supplementary material, which is available to authorized users.

Long non-coding RNA SOX2OT promotes the stemness phenotype of bladder cancer cells by modulating SOX2

“…Long non-coding RNAs (lncRNAs) are an important group of transcribed RNA molecules that have a length greater than 200 nucleotides [13]. The rapid development of RNA genomics has highlighted the role of lncRNAs in many human diseases, especially in cancers [14][15][16][17][18][19]. Recent accumulating evidence has indicated that lncRNAs, such as BLACAT2, UCA-1, LNMAT1 and PANDAR, play important regulatory roles in diverse biological processes in bladder cancer [20][21][22][23][24][25].…”

Cancer‐associated fibroblasts–derived exosomes‐mediated transfer of LINC00355 regulates bladder cancer cell proliferation and invasion

“…Studies have found that long noncoding RNAs (lncRNAs) can be expressed in exosomes derived from tumor serum, cells, and microenvironment . Studies have shown that serum and urine exosome lncRNA can be used as biomarkers for the diagnosis and prognosis of BC . In addition, exosomal lncRNA is also involved in the regulation of BC development .…”

Exosomal lncRNAs: the newest promising liquid biopsy

“…Exosomal lncRNAs can be also isolated from other body fluids rather than the most common, such as plasma or serum. For instance, Zhan et al [35] validated a panel of three lncRNAs (MALAT1, PCAT-1 and SPRY4-IT1) by RT-qPCR, in urine exosomes (UE) of 80 bladder cancer patients and 80 healthy controls, and found a significant overexpression in bladder cancer patients. The verification of the diagnostic capacity indicated a much better performance for this panel than for the urine cytology, which is widely used in clinical practice.…”