Abstract 281P
Background
Bladder Urothelial Carcinoma (BLCA) and Upper Tract Urothelial Cancer (UTUC) have been speculated to derive from similar cellular origins. However, recent studies have highlighted both molecular properties and therapeutic response were significantly different between the two entities. Therefore, we aim to further dissect and identify molecular diversity as well as clinical utility between two diseases in East Asian urothelial cancer patients.
Methods
175 BLCA and 56 UTUC patients were enrolled from the K-master consortium and subjected to NGS panels to detect major genomic aberrations.
Results
Interestingly, ERBB2 and ERCC2 mutations were significantly enriched in BLCA, while a mutation in BRIP1 was prominent in UTUC. Pathway analysis further discovered that the RTK pathway is highly activated in BLCA while RAS was predominant in UTUC. BLCA was distinguished by increased proliferation kinetics, whereas UTUC was distinguished by enhanced invasiveness and migratory capabilities. Furthermore, pharmacogenomic analysis revealed that TP53 mutations were significantly enriched in non-responders, while mutations in FGFR3 and KRAS were highly observed in responders. Immune checkpoint blockades demonstrated that BLCA patients exhibited relatively favorable response compared to UTUC patients and MTOR mutations were highly selective in the responder group.
Conclusions
In this study, we looked at the genetic difference of BLCA and UTUC using mutation data in K-MASTER program, and published rna-seq data, while TCGA and MSK. BLCA is more characterized by rapid proliferation kinetics, while UTUC is marked by increased activity or invasiveness and migratory capability. RTK is activated in BLCA and RAS is activated in UTUC. It looks like BLCA is more immune-enriched compared to UTUC, which is consistent with previous reports. Forthermore, pharmacogenomic analysis revealed the relationship between the difference and drug reactivity. This studies suggest that drugs should be used independently for UTUC unlike BLCA in the clinical research, and provide a clue on what points to focus on future BLCA and UTUC research.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The author.
Funding
Has not received any funding.
Disclosure
The author has declared no conflicts of interest.