Comprehensive Molecular Characterization of Muscle-Invasive Bladder Cancer

Abstract

It has come to our attention that we inadvertently used the wrong synonymous name for PD-L1 in the Discussion section on page 551. Instead of CD270, which is a synonymous name for the HVEM receptor, we should have used CD274 in that sentence. This error has been corrected online. We apologize for any confusion this may have caused.

Basal‐subtype bladder tumours show a ‘hot’ immunophenotype

“…In summary, we have shown that characterising the immune infiltrate is relevant in the evaluation of bladder cancer, and that basal-subtype UC shows a characteristic 'hot' immunophenotype (an abundance of cytotoxic T cells with increased inhibitory molecular expression) with increased CD8 and PD-1 expression and increased CD8/FOXP3 ratios, in addition to numbers of increased PD-L1-expressing cells, as compared with luminal-subtype UC. These findings are in agreement with TCGA data, 18 and highlight the possibility that IC typing may be useful in the stratification of patients with UC who may be involved in clinical trials, as it can be theorised that certain patients (e.g. those with a 'hot immunophenotype') may benefit from upfront alternative treatment regimens with immunotherapeutic agents, in contrast to patients without such a phenotype, who are more likely to respond to more traditional agents.…”

“…Although statistically significant differences in survival were not observed between patients with luminal-subtype and basal-subtype tumours, a trend was 26 and, in the recently updated bladder TCGA dataset, the combined luminal-subtype groups accounted for 60% of cases and the basal-subtype group for 35% of cases. 18 Our TMA was constructed from tumours with <50% divergent differentiation, which may explain the lower proportion basal-subtype tumours in this study. We chose to exclude double-negative cases (i.e.…”

Molecular changes during progression from nonmuscle invasive to advanced urothelial carcinoma

“…The vast majority (IHC: 92% and mRNA: 87%) of this cohort was classified as "luminal-like" subtypes Uro or GU, which in more advanced stages make up only about 50%. 28,30,44 The dynamics of molecular subtypes in the cohort was interesting: Patients that progressed with the Uro subtype tended to have only prior Uro tumors; patients that progressed with the GU subtype, tended to have either Uro or GU prior tumors; and patient that progressed with nonluminal subtypes had few prior tumors that could be of any subtype. These data explain to some degree why certain subtypes are more frequent at different disease stages.…”

Proteome‐based classification of Nonmuscle Invasive Bladder Cancer

“…This subtype also showed increased abundance of several luminal proteins such as KRT20 and epithelial cytokeratins expressed by semi-or terminally differentiated cells (KRT8/KRT18 and KRT7/KRT19), 3 as well as of uroplakins (UPK2, UPK1B and UPK3BL1), and other luminal proteins (GPX2, SRC and ADIRF), earlier reported to be at increased abundance in low risk tumors. 5,6,11,32 Tumors with high levels of proteins potentially involved in epithelial-to-mesenchymal transition (EMT; VIM, COL1A, COL1A2, TGFBI and CAV1), 5 as well as markers of stromal infiltration (ACTA2, DES, TAGLN and COL6A3), 33,34 and structural components of the extracellular matrix (ECM), like proteoglycans (LUM, DCN, BGN and PRELP) 33 coclustered in NPS2. Features of inflammation (S100A8, S100A9, SND1 and RNF213), cytokine signal transduction (STAT1, STAT3 and DHX9) and angiogenesis (HMGB1, HMGB2 and TYMP) were all at highest levels in NPS1.…”