Dados do Trabalho

Título

TRANSCRIPTOMIC FEATURES ASSOCIATED WITH RECURRENCE IN UPPER TRACT UROTHELIAL CARCINOMA (UTUC)

Introdução e Objetivo

While UTUC comprises only 5-10% of urothelial tumors, the 5-year disease specific survival rate is <50% after extirpative surgery for patients with pT2/T3 disease and <10% for patients with pT4 disease. Studying the molecular and genomic landscape of UTUC as a distinct entity from urothelial carcinoma of the bladder (UCB) has been important for the development of targeted therapies and can be helpful in improving risk-stratification, and guiding treatment selection. The aim was to identify transcriptomic and genomic signatures that may help predict disease prognosis in patients with UTUC.

Método

Total RNA was isolated using Trizol from frozen tissue blocks obtained from 100 patients with nonmetastatic UTUC that underwent radical nephroureterectomy. TruSeq RNA Library Prep Kit v2 (Illumina) was used for library preparation, followed by sequencing on an Illumina HiSeq 2500. RNA-seq gene level count values were computed using the R package GenomicAlignments over aligned reads with UCSC KnownGene in hg19 as the base gene model. The ssGSEA method was used for bulk RNA-seq deconvolution analysis. 

Resultados

Conclusão

Clustering analysis based on cNMF identified 5 transcriptomically distinct UTUC clusters (1), with C1 and C2 being associated with a higher rate of disease recurrence and decreased disease specific survival (2). GSEA (3) and immune deconvolution analysis revealed that C1 shows enrichment in inflammatory pathways while C2 exhibits higher CD8 infiltration. C1 followed by C2 also had the highest scores for immunesuppresion and immunecheckpoints, expressing higher levels of PD1 and PDL1, which are commonly targeted by immunotherapy.