Abstract
BackgroundThe recent discovery of miRNAs and lncRNAs in urine exosomes has emerged as promising diagnostic biomarkers for bladder cancer (BCa). However, mRNAs as the direct products of transcription has not been well evaluated in exosomes as biomarkers for BCa diagnosis. The purpose of this study was to identify tumor progression-related mRNAs and lncRNAs in urine exosomes that could be used for detection of BCa.MethodsRNA-sequencing was performed to identify tumor progression-related biomarkers in three matched superficial tumor and deep infiltrating tumor regions of muscle-invasive bladder cancer (MIBC) specimens, differently expressed mRNAs and lncRNAs were validated in TCGA dataset (n = 391) in the discovery stage. Then candidate RNAs were chosen for evaluation in urine exosomes of a training cohort (10 BCa and 10 healthy controls) and a validation cohort (80 BCa and 80 healthy controls) using RT-qPCR. The diagnostic potential of the candidates were evaluated by receiver operating characteristic (ROC) curves.ResultsRNA sequencing revealed 8 mRNAs and 32 lncRNAs that were significantly upregulated in deep infiltrating tumor region. After validation in TCGA database, 10 markedly dysregulated RNAs were selected for further investigation in urine exosomes, of which five (mRNAs: KLHDC7B, CASP14, and PRSS1; lncRNAs: MIR205HG and GAS5) were verified to be significantly dysregulated. The combination of the five RNAs had the highest AUC to disguising the BCa (0.924, 95% CI, 0.875–0.974) or early stage BCa patients (0.910, 95% CI, 0.850 to 0.971) from HCs. The expression levels of these five RNAs were correlated with tumor stage, grade, and hematuria degrees.ConclusionsThese findings highlight the potential of urine exosomal mRNAs and lncRNAs profiling in the early diagnosis and provide new insights into the molecular mechanisms involved in BCa.
Highlights
Bladder cancer (BCa) is the tenth most common cancer type worldwide [1]
The biomarkers collected complied with the criteria as follows: [1] to ensure that candidate RNAs are tumor-related and can be detected in urine exosomes, especially in patients with early stage BCa, dysregulated RNAs obtained by RNA-seq were upregulated in deep infiltrating tumor regions as previously described [18]; [2] the average expression of candidate RNAs were between 3 and 50 to avoid biomarkers concentration that were too low to be detected in urine exosomes or housekeeper genes rather than tumor-related genes; [3] candidate biomarkers were upregulated in BCa tissues compared to adjacent normal tissues in The Cancer Genome Atlas (TCGA) cohort, P < 0.05
To assess dysregulated mRNAs and lncRNAs in multiple regions of muscle-invasive bladder cancer (MIBC), we conducted RNA sequencing between three matched superficial tumor regions and deep infiltrating tumor regions of MIBC
Summary
Bladder cancer (BCa) is the tenth most common cancer type worldwide [1]. The incidence of BCa is approximately four times higher in men than in women, and BCa mostly affects older people [2]. Approximately 75% of newly diagnosed patients of BCa are non–muscle invasive bladder cancer (NMIBC), which is associated with a 5-yr survival of 90% [3]. Some urine tumor markers, such as the nuclear matrix protein 22 (NMP22) [8] and bladder tumor antigen (BTA) [9] have been approved by The Food and Drug Administration (FDA) for BCa diagnosis. Due to their moderate assay performance, high cost and may be falsely elevated in benign conditions [10], widespread adoption of such assays has not been occurred.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
