Urothelial cancer, also called bladder cancer, typically presents in patients over 50 years and is approximately three times as common in males compared to females. Tobacco is considered an important risk factor for developing bladder cancer. By using a systems level approach to analyze the urothelial cancer proteome based on clinical metadata and genome-wide transcriptomics data, 1093 genes were found to be associated with prognostic outcome.

Urothelial cancer develops in the urinary bladder, but can also arise from the renal pelvis, ureters or urethra. Urothelial cancer can be divided into papillary and non-papillary tumors depending on the morphological appearance. Approximately 25% of all urothelial tumors are non-invasive papillary tumors. However, 10-15% of these patients will subsequently develop an invasive tumor.

The analysis of prognostic genes in urothelial cancer was based on publicly available gene expression data and clinical metadata from the Cancer Genome Atlas (TCGA), consisting of 406 patients with different stages of urothelial cancer. According to the analysis, 1093 genes were associated with prognostic outcome, out of which 379 genes were associated with unfavorable prognosis and 714 genes with favorable prognosis.

EHBP1 is shown to be associated with unfavorable prognosis in patients with urothelial cancer. The gene encodes a protein that may play a role in endocytic trafficking and EHBP1 has previously been linked to an aggressive form of prostate cancer. Immunohistochemical staining of EHBP1 shows a differential cytoplasmic expression pattern in urothelial cancer (Figure 1).

The vesicle-associated membrane protein 8, or VAMP8 gene, is shown to be associated with favorable prognosis in urothelial cancer. The VAMP8 protein is a member of the soluble N-ethylmaleimide-sensitive factor-attachment protein receptors (SNARE) and plays an important role in the vesicle fusion of the autophagosome membrane and lysosome membrane. Immunohistochemical staining of VAMP8 shows staining of varying intensity in samples from patients with urothelial cancer (Figure 2).

Explore the Urothelial Cancer Proteome and search for your gene of interest in our Pathology Atlas!

More information about the Pathology Atlas is available in the research article published in Science (Uhlén et al. 2017). You can also read a brief summary here.

References

Uhlén M et al, 2017. A Pathology Atlas of the Human Cancer Transcriptome. SciencePubMed: 28818916 DOI: 10.1126/science.aan2507

Histology dictionary - Urothelial cancer

Feria Hikmet Noraddin