Identification of a panel of lncRNAs derived from urinary extracellular vesicles as non-invasive diagnostic biomarkers for bladder cancer

Abstract

Bladder cancer (BLCA) is a common malignant tumor of the urinary system and is histopathologically divided into high-grade and low-grade BLCA. Accurate diagnosis of BLCA and high-grade BLCA are critical for clinical treatment and early intervention. High-throughput RNA-seq was performed to explore dysregulated long non-coding RNAs (lncRNAs) in urinary extracellular vesicles (uEVs) from BLCA patients, and their expression levels were examined in a large cohort of uEVs samples using qRT-PCR. We examined the expression levels and subcellular localization of the lncRNAs in BLCA tissues and cell lines. We analyzed the correlation between the expression levels of lncRNAs in uEVs and clinical parameters and assessed their clinical value as diagnostic biomarkers for BLCA and high-grade BLCA using receiver operating characteristic (ROC) curve. Through high-throughput RNA-seq, we identified several dysregulated lncRNAs (MALAT1, SCARNA10, LINC00963 and LINC01578) in uEVs from BLCA patients. The lncRNAs were significantly upregulated in uEVs of BLCA patients, however with varying expression levels in tissues and cell lines. The lncRNAs are predominantly localized in the nucleus of BLCA cell lines. Elevated expression levels of the lncRNAs were associated with adverse factors, including higher tumor grade and larger tumor diameter. ROC curve analysis showed that the combination of four lncRNAs in uEVs and the existing marker nuclear matrix protein 22 provided substantial diagnostic value for BLCA and high-grade BLCA, with area under curve values of 0.900 and 0.917, respectively. The lncRNA panel derived from uEVs may serve as a promising non-invasive biomarker for diagnosing BLCA and high-grade BLCA.