6.0 Conclusion and future perspective

Urothelial cell carcinoma (UCC) is among the prime causes of malignancy-associated deaths globally and its aetiology is poorly understood. The bladder cancer progression is a multifaceted process that is extremely heterogeneous and complicated. Thus, requiring the use of advanced transcriptome technology like RNA-sequencing (RNA-Seq) to better understand the disease phenotypes. The RNA-Seq studies of bladder cancer reviewed in this paper reveal genome-wide changes among different classes of bladder cancer and its pathogenicity that includes; dysregulated genes and pathways. Moreover, the possibilities to better understand the molecular mechanism underlying UCC progression has been successful through application of RNA-sequencing as this helps in understanding pathogenesis, discovering biomarkers and uncovering the mechanism of drug resistance in bladder cancer.
Despite the progressive improvement provided by RNA-Seq technologies in understanding the molecular basis for UCC pathogenesis, there is still a lot to be done to prevent a recurrence, prevent further metastasis of the malignant cells and reduce cancer-related death due to UCC. A good number of dysregulated genes and biomarkers have been implicated in bladder cancer, and the uses of these genes clinically have provided controversial results. Hence, there has not been a single prognostic and diagnostic biomarker that are successfully translated into clinical application. This opens up an avenue for a potential research space to fully understand bladder cancer. To address the current limitations, there is a need to have a standard pipeline and integrated multiple experiments analyses as a reference point for all studies due to the high recurrence nature of UCC. The existence of molecular subsets of cellular signatures and microenvironment promotes measures which could avoid therapeutic failures exposed by RNA-Seq study. Although, the acceptability of RNA-Seq regarding gene expression in UCC led to existence of incompatibility due to RNA-Seq techniques and variability in platform application.
In summary, RNA-Seq is regarded as the golden standard for large scale high-throughput genome-wide and gene expression studies. It has provided us an unknown insight into the transcriptional changes in bladder cancer diagnosis and management. As the cost of sequencing is gradually decreasing and more precision is being obtained in most of the computational tools, RNA-Seq technology will continue to be applied in studying bladder cancer transcriptomics and disease state. Consequently, an in-depth exploration of the complex and stochastic genetic nature of bladder cancer could possibly result in a novel biomarker discovery and identifying new therapeutic strategies. Moreover, single cell sequencing (scRNA-Seq) may offer a better option for comprehensive understanding of UCC development and recurrence and could effectively help in improving bladder cancer management.