Bladder cancer is one of the most common urological malignancies worldwide, and approximately 90% of bladder cancer cases are histologically typed as bladder urothelial carcinoma (BLCA). Exosomes are 30 to 200 nm extracellular vesicles that transport microRNAs, long noncoding RNAs (lncRNAs), mRNAs, circular RNAs, and proteins across tissues and through circulation. Urinary exosomes may contain genetic information from tumor cells. Researchers from the Tongji University School of Medicine explored the clinical significance of urinary exosomal lncRNA telomerase RNA component (TERC) levels to provide an urgently needed diagnostic and prognostic biomarker for BLCA.
In this study, the researchers used RNA-sequencing of samples from four BLCA patients and three healthy controls to identify that TERC was differentially expressed in urinary exosomes. They then used quantitative PCR in different types of clinical samples to validate the biomarker and analyzed results using receiver operating characteristic curves.
The researchers found that TERC was significantly upregulated in urinary exosomes from BLCA patients compared with those from healthy controls (P < 0.0001). Urinary exosomal TERC showed higher sensitivity (78.65%) and accuracy (77.78%) than existing indicators including nuclear matrix protein-22 and urine cytometry. Using the cut-off value 4.302, the area under the curve for urinary exosomal TERC was 0.836 (95% confidence interval: 0.768-0.891, P < 0.0001). Furthermore, this noninvasive assay could distinguish low-grade and high-grade tumors (P = 0.0153).
RNA-Sequencing of Urinary Exosomes
Heat map and volcano plot of differentially expressed long noncoding RNAs (DE-lncRNAs) from urinary exosomes. (a) Heat map of all DE-lncRNAs from urinary exosomes of healthy controls and bladder urothelial carcinoma (BLCA) patients. Results of the differential analysis are shown (), with color from green to red indicating low to high fragments per kilobase of exon per million mapped fragments (FPKM) of DE-lncRNAs. (b) Volcano plot of RNA-sequencing results. Green dots represent downregulated genes and red dots represent upregulated genes.
TERC is enriched in urinary exosomes from BLCA patients. Urinary exosomal TERC could become a diagnostic and prognostic biomarker for BLCA that allows clinicians to realize noninvasive detection of BLCA.