Diagnostic and prognostic value of long noncoding RNAs as biomarkers in urothelial carcinoma

Abstract

Many long noncoding RNAs (lncRNAs) are deregulated in cancer and contribute to oncogenesis. In urothelial carcinoma (UC), several lncRNAs have been reported to be overexpressed and proposed as biomarkers. As most reports have not been confirmed independently in large tissue sets, we aimed to validate the diagnostic and prognostic value of lncRNA upregulation in independent cohorts of UC patients. Thus, expression of seven lncRNA candidates (GAS5, H19, linc-UBC1, MALAT1, ncRAN, TUG1, UCA1) was measured by RT-qPCR in cell lines and tissues and correlated to clinicopathological parameters including follow-up data (set 1: N n = 10; T n = 106). Additionally, publicly available TCGA data was investigated for differential expression in UC tissues (set 2: N n = 19; T n = 252,) and correlation to overall survival (OS). All proposed candidates tended to be upregulated in tumour tissues, with the exception of MALAT1, which was rather diminished in cancer tissues of both data sets. However, strong overexpression was generally limited to individual tumour tissues and statistically significant overexpression was only observed for UCA1, TUG1, ncRAN and linc-UBC1 in tissue set 2, but for no candidate in set 1. Altered expression of individual lncRNAs was associated with overall survival, but not consistently between both patient cohorts. Interestingly, lower expression of TUG1 in a subset of UC patients with muscle-invasive tumours was significantly correlated with worse OS in both cohorts. Further analysis revealed that tumours with low TUG1 expression are characterized by a basal-squamous-like subtype signature accounting for the association with poor outcome. In conclusion, our study demonstrates that overexpression of the candidate lncRNAs is found in many UC cases, but does not occur consistently and strongly enough to provide reliable diagnostic or prognostic value as an individual biomarker. Subtype-dependent expression patterns of lncRNAs like TUG1 could become useful to stratify patients by molecular subtype, thus aiding personalized treatments.

RNA-Sequencing Data Reveal a Prognostic Four-lncRNA-Based Risk Score for Bladder Urothelial Carcinoma: An in Silico Update

“…Study population RNA-sequencing reads per kilobase million (RPKM) data of patients with BLCA were obtained from TCGA [12,25]. The cohort contained 433 samples, including 414 tumor tissue samples and 19 non-tumor adjacent bladder tissue samples.…”

The role of long non‐coding RNAs in multiple myeloma

“…The results revealed that the level of TUG1 was significantly higher in MM patients than in healthy volunteers, indicating that TUG1 may play a role in disease progression in MM. Furthermore, it has been observed that higher TUG1 expression levels are associated with the disease state in bladder carcinoma samples . Functional studies have revealed that TUG1 is induced in a p53‐dependent manner, bounds to polycomb repressive complex 2 (PRC2), and plays a role in repressing important cell cycle‐related genes .…”

“…48 In addition, Nagoshi et al also found that the rearrangement of the PVT1 gene was frequently observed in MM harboring 8q24 rearrangements, which are associated with tumor progression. 51 PVT1 has been reported to be involved in variants t(2;8), t(8;22), or t (8;14) in human Burkitt lymphoma, 52,53 and its overexpression has been responsible for the suppression of apoptosis. 54 Furthermore, several studies have reported the breakpoints within a region centromeric to PVT1, suggesting that PVT1 is one of the target genes of rearrangement that may play a role in driving MM.…”

“…Furthermore, it has been observed that higher TUG1 expression levels are associated with the disease state in bladder carcinoma samples. 53,59 Functional studies have revealed that TUG1 is induced in a p53-dependent manner, bounds to polycomb repressive complex 2 (PRC2), and plays a role in repressing important cell cycle-related genes. 59 In addition, a number of studies have reported that deregulated PRC2-related lncRNA expression is associated with tumorigenesis and progression.…”

Circular RNA circARNT2 Suppressed The Sensitivity of Hepatocellular Carcinoma Cells to Cisplatin by Targeting The miR-155-5p/PDK1 Axis

“…Moreover, circRNAs regulate malignant behaviors of cancer cells, such as proliferation, apoptosis resistance, migration, invasion and drug resistance 14,15 . Although several circRNAs have been reported to participate in the tumorigenesis and progression of HCC [16][17][18] , the expressions and roles of circRNA in chemoresistance of HCC remains unclear.…”