Abstract
BACKGROUND: Bladder urothelial carcinoma (BLCA) is still one of the most malignant diseases and has a dismal outcome. Angiogenesis has confirmed its critical role in the development of malignant neoplasms. In this study, we uncovered the prognostic implications of the angiogenesis-related gene panel in urothelial tumors. METHODS: The RNA-seq data and clinical records of 402 patients with BLCA were collected from the TCGA database. The panel, including 145 genes involved in angiogenesis, was retrieved from the Uniprot database and the published work. The patients with similar expressed profiles were clustered, and the differences in gene expression were compared. The correlation of gene expression and BLCA outcomes or clinical features were analyzed. RESULTS: There were two clusters of BLCA patients identified on the expressed basis of angiogenesis-related genes. A significant difference was detected in the tumor stages between the two clusters (P<0.001) and a striking advantaged prognosis shown in cluster_1 (86.83 vs. 27.06 months, P=0.001). According to statistics, 115 genes showed a discrepancy in expression between the two clusters, and 16 genes positively correlated to tumor stage progression. Separately analyzed the correlation of those stage-related genes and overall survivals (OS) revealed that high expression of 8 genes, including ECM1 (HR =1.72, P<0.001), FN1 (HR =1.564, P=0.004), FGF1 (HR =1.519, P=0.005), FAP (HR =1.449, P=0.020), JAM3 (HR =1.396, P=0.026), THBS1 (HR =1.402, P=0.028), MFGE8 (HR =1.394, P=0.028) and COL8A2 (HR =1.388, P=0.035), were showed worse prognosis of BLCA, respectively. CONCLUSIONS: This study showed an integrated profile of angiogenesis-related genes and identified the different BLCA subgroups with favorable prognosis and poor prognosis depended on the expression pattern of angiogenesis-related genes. Furthermore, this work revealed the single gene expressions of ECM1, FN1, FGF1, FAP, JAM3, THBS1, MFGE8 and COL8A2 involved in angiogenesis associated the prognosis remarkably.