Urinary exosomal long non-coding RNAs as noninvasive biomarkers for diagnosis of bladder cancer by RNA sequencing

Abstract

IntroductionCystoscopy is the standard methodology for diagnosis of bladder cancer (BC), but it is invasive and relatively expensive. Previous studies have found that urinary exosomal long non-coding RNAs (lncRNAs) may act as potential noninvasive biomarkers for diagnosis. Here we identified urinary exosomal lncRNAs that are differentially expressed between BC and controls, and established a panel for diagnosis of BC.MethodsWe performed RNA sequencing in urinary exosomes of 7 controls and 7 patients, subsequently the differentially expressed lncRNAs were detected in training cohort (50 controls and 50 patients) and validation cohort (43 controls and 43 patients). The diagnostic power of lncRNAs for BC was calculated by the area under curve (AUC). The panel for diagnosis of BC was calculated by logistic regression.ResultsThe results of RNA sequencing in urinary exosomes showed that 240 upregulated lncRNAs and 275 downregulated lncRNAs were differentially expressed. The levels of MKLN1-AS, TALAM1, TTN-AS1 and UCA1 in BC patients were higher than that in controls in the training and validation cohort by real-time PCR. Using logistic regression, with the combination of these four lncRNAs and NMP22, we identified a panel of five parameters capable of classifying BC patients versus controls on the basis of the training cohort (AUC=0.850). Moreover, the performance of the panel exhibited better performance than either single parameter in the validation cohort.ConclusionCollectively, this study confirmed the diagnostic value of lncRNAs for BC by high-throughout urinary exosomal RNA sequencing.

Circulating tumor cell-derived exosome–transmitted long non-coding RNA TTN-AS1 can promote the proliferation and migration of cholangiocarcinoma cells

“…Moreover, exosomal delivery of TTN-AS1 derived from gastric cancer cells can promote gastric cancer progression [ 38 ]. Elevated levels of exosomal LncRNA TTN-AS1 expression have been observed in bladder cancer and have diagnostic value [ 39 ]. In our previous studies, we identified high expression of LncRNA TTN-AS1 in cholangiocarcinoma tissues.…”

KLHDC7B as a novel diagnostic biomarker in urine exosomal mRNA promotes bladder urothelial carcinoma cell proliferation and migration, inhibits apoptosis

“…In bladder cancer, exosomes mediate cell communication through nucleic acid and protein delivery 16 . Exosomal RNA from urine has previously been tested as a noninvasive biomarker for the diagnosis of bladder cancer, such as the combination of MALAT1, PCAT‐1, and SPRY4‐IT1 with a diagnostic AUC of 0.813 (sensitivity = 62.5%, specificity = 85.0%) 17 ; MKLN1‐AS, TALAM1, TTN‐AS1, and UCA0 18 have AUC values between 0.752 and 0.808 in bladder cancer diagnosis, with a combined diagnostic AUC of 0.850 and sensitivity of 72% and specificity of 82% with NMP22. In our previous study, we demonstrated that KLHDC7B is a potential bladder cancer urinary exosome‐derived biomarker, significantly upregulated in the urine of bladder cancer patients 7 .…”

Exosomes: Diagnostic and Therapeutic Implications in Cancer

“…The expression levels of exosomal miR-21, miR-155, miR-182, and miR-373 in the serum of breast cancer patients are higher than those in healthy controls [ 91 ]. Urinary exosomal lncRNAs can distinguish bladder cancer patients from healthy controls based on RNA sequencing [ 92 ]. Compared to healthy controls, salivary exosomal miR-486-5p is elevated and miR-10b-5p is reduced in oral and oropharyngeal squamous cell carcinoma [ 93 ].…”