Roudnicky F, et al. Am J Pathol 2020.
Tumor-associated blood vessels differ from normal vessels and play key roles in tumor progression. We aimed at identifying biomolecules that are differentially expressed in human bladder cancer-associated blood vessels in order to find novel biomarkers and mechanisms involved in tumor-associated angiogenesis. We compared the transcriptome of tumor blood vasculature from human invasive bladder carcinoma (I-BLCA) and normal bladder tissue vasculature and performed differential expression and
unsupervised hierarchical clustering analyses. Pathway analysis identified upregulation of genes involved in proliferation, cell cycle, angiogenesis, inflammation and TGFβ signaling in tumor blood vasculature. We then compared bladder cancer tumor blood vasculature to tumor blood vasculature of other solid cancers and identified a common "consensus" gene expression signature. This gene expression signature correlated with overall survival of patients suffering from several of the solid cancers investigated in the TCGA dataset. In bladder tumor blood vasculature, we focused on a secreted factor ANGPTL2 that we confirmed upregulation by qRT-PCR and immunohistochemical staining. We also measured ANGPTL2 levels in plasma and observed upregulation of ANGPTL2 in NI-BLCA an I-BLCA. We semi-quantitively analyzed the expression of ANGPTL2 in tissue microarrays from I-BLCA and found surprisingly an opposite correlation between staining intensity and progression-free survival in the I-BLCA. Our results indicate that ANGPTL2 might serve as a potential biomarker to predict progression-free survival in I-BLCA.