Unraveling UCA1 lncRNA prognostic utility in urothelial bladder cancer

Abstract

In the era of precision oncology, bladder cancer (BlCa) is characterized by generic patient management and lack of personalized prognosis and surveillance. Herein, we have studied the clinical significance of urothelial cancer associated 1 (UCA1) lncRNA in improving patients’ risk stratification and prognosis. A screening cohort of 176 BlCa patients was used for UCA1 quantification. The Hedegaard et al. (n = 476) and The Cancer Genome Atlas (TCGA) provisional (n = 413) were analyzed as validation cohorts for non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC), respectively. Patients’ survival outcome was assessed using recurrence and progression for NMIBC or death for MIBC as clinical endpoint events. Bootstrap analysis was performed for internal validation of Cox regression analysis, whereas the clinical benefit of disease prognosis was assessed by decision curve analysis. UCA1 was significantly overexpressed in bladder tumors compared with normal urothelium, which was confirmed only in the case of NMIBC. Interestingly, reduced expression of UCA1 was correlated with muscle-invasive disease as well as with tumors of higher stage and grade. UCA1 loss was strongly associated with higher risk of short-term relapse [hazard ratio (HR) = 1.974; P = 0.032] and progression to invasive stages (HR = 3.476; P = 0.023) in NMIBC. In this regard, Hedegaard et al. and TCGA validation cohorts confirmed the unfavorable prognostic nature of UCA1 loss in BlCa. Finally, prognosis prediction models integrating UCA1 underexpression and established clinical disease markers contributed to improved stratification specificity and superior clinical benefit for NMIBC prognosis. Underexpression of UCA1 correlates with worse disease outcome in NMIBC and contributes to superior prediction of disease early relapse and progression as well as improved patient stratification specificity.

The lncRNA DLX6-AS1 promoted cell proliferation, invasion, migration and epithelial-to-mesenchymal transition in bladder cancer via modulating Wnt/β-catenin signaling pathway

“…In the bladder cancer studies, various dysregulated lncRNAs have been identified in both bladder cancer tissues and cells. For examples, Avgeris et al [10] screened a cohort of 176 bladder cancer patients, and identified lncRNA urothelial cancer associated 1 (UCA1) as a superior prognostic factor of disease early-relapse and progression in the bladder cancer patients. Liu et al [11] revealed that lncRNA neuroblastoma-associated transcript 1 exerted the tumor-suppressive effects on the malignant bladder cancer cells via regulating miR-21/suppressor of cytokine signaling 6 axis.…”

LINC00511/miRNA-143-3p Modulates Apoptosis and Malignant Phenotype of Bladder Carcinoma Cells via PCMT1

“…The differential expression of lncRNA in malignant tumors and the molecular mechanism of action have been gradually investigated, and more and more lncRNAs have been found to be closely related to the occurrence and development of tumors. Some lncRNAs, such as ITGB1, UCA1, and DUXAP10, have been reported to play a key role in bladder cancer, significantly affecting the proliferation, migration, invasion, drug resistance, and other malignant biological behaviors of bladder cancer cells, and are correlated with early diagnosis, recurrence, metastasis, and prognosis of bladder cancer (Lv et al, 2018;Avgeris et al, 2019;Dai et al, 2019). LINC00511 is a newly discovered lncRNA with an oncogenic function, which can promote the proliferation and invasion of tumor cells by regulating miRNA expression (Wu et al, 2020;Zhang et al, 2020).…”

The Landscape of Long Non-Coding RNA Dysregulation and Clinical Relevance in Muscle Invasive Bladder Urothelial Carcinoma

“…Studies using GENCODE annotations would only examine 19,812 transcripts, compared to the 107,039 transcripts in LNCipedia [10]. Previous studies have identified that lncRNAs like LINC00460, UCA1, LINC00958, LINC01296, SNH12, and DUXAP8 are implicated in bladder cancer, but did not examine the entire landscape of lncRNA transcripts [11,18,20,21].…”