IBCN 2018: Defining the Proteomic Landscape of Non – Muscle Invasive Bladder Cancer

Rotterdam, The Netherlands (UroToday.com) Antonia Vlahou presented work regarding proteomic definition of bladder cancer subtypes aiming to fill existing gaps and define optimal patient management schemes. They analyzed 98 fresh-frozen tissue samples from non-muscle invasive bladder cancer (58 pTa and 40 pT1) by high-resolution proteomics (LC-MS/MS). Limiting to peptides identified with high confidence at a frequency threshold of at least 20%, 1309 proteins could be assessed. Clustering (k-means) indicated stability for k = 3 classes. These differed in size (class 1: 17; class 2: 42 and class 3: 39 members), and stage and grade: (class 1: mostly pT1, grade III; class 2: representation of all grades-stages, class 3: mainly pTa-low grade tumors; Fisher’s exact p < 0.001).

Basal, cancer stem cell and inflammation markers were upregulated in class 1, whereas luminal markers were found increased in class 3 cancers. Class 2 exhibited a mesenchymal phenotype. Further molecular characterization combined with pathway and gene set functional assessment suggested a high-risk proteome signature for class 1 and best prognosis for class 3.

To validate this observation, 19 muscle invasive tumors (MIBC, pT2+) were also analyzed by proteomics. Principal component analysis indicated the higher proximity of class 1 and, conversely, a greater distance of class 3, to the proteome observed for MIBC, while classification of the 19 MIBC to the three consensus subclasses resulted in assignments of MI tumors mainly to classes 1 and 2.

In summary, they found the existence of distinct protein-based subtypes of NMIBC placing them in the context of current stratification schemes. The summary of pathways according to proteomics may further aid to the prognostic molecular subtype classification system.

Presented by: Antonia Vlahou, PhD, Biomedical Research Foundation, Academy of Athens, Athens, Greece 

Written by: Stephen B. Williams, M.D., Associate Professor, Division of Urology, The University of Texas Medical Branch, Galveston, TX. and Ashish M. Kamat, M.D. Professor, Department of Urology, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX at the 16th Annual Meeting of the International Bladder Cancer Network (IBCN) October 11-13, 2018 - the Inntel Hotels Rotterdam Centre, Rotterdam, The Netherlands