Abstract
Simple SummaryBladder cancer is a heterogeneous disease with high recurrence rates. The current prognostication depends on tumor stage and grade and there is a need for predictive biomarkers that can distinguish between progressive versus non-progressive disease. We have identified a 3-gene signature panel having prognostic value in bladder cancer, which could aid in clinical decision making.Bladder cancer prognosis remains dismal due to lack of appropriate biomarkers that can predict its progression. The study aims to identify novel prognostic biomarkers associated with the progression of bladder cancer by utilizing three Gene Expression Omnibus (GEO) datasets to screen differentially expressed genes (DEGs). A total of 1516 DEGs were identified between non-muscle invasive and muscle invasive bladder cancer specimens. To identify genes of prognostic value, we performed gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. A total of seven genes, including CDKN2A, CDC20, CTSV, FOXM1, MAGEA6, KRT23, and S100A9 were confirmed with strong prognostic values in bladder cancer and validated by qRT-PCR conducted in various human bladder cancer cells representing stage-specific disease progression. ULCAN, human protein atlas and The Cancer Genome Atlas datasets were used to confirm the predictive value of these genes in bladder cancer progression. Moreover, Kaplan–Meier analysis and Cox hazard ratio analysis were performed to determine the prognostic role of these genes. Univariate analysis performed on a validation set identified a 3-panel gene set viz. CDKN2A, CTSV and FOXM1 with 95.5% sensitivity and 100% specificity in predicting bladder cancer progression. In summary, our study screened and confirmed a 3-panel biomarker that could accurately predict the progression and prognosis of bladder cancer.
Highlights
Bladder cancer is a heterogeneous disease with high prevalence and recurrence rates [1]
We identified a subset of seven genes, which include CDKN2A, cell division cycle protein 20 (CDC20), CTSV, FOXM1, keratin 23 gene (KRT23), MAGEA6, and S100A9 (Table 2)
We found that higher expression of CDC20, CTSV, KRT23, and S100A9 correlate with poor survival, whereas lower expression of CDKN2A and FOXM1 were indicative of poor survival (Figure 8)
Summary
Bladder cancer is a heterogeneous disease with high prevalence and recurrence rates [1]. About 70–80% of NMIBC tumors are confined to the epithelium or sub-epithelial connective tissue [3]. These tumors are frequently managed by surgery and/or immunotherapy based on their risk of progression assessment. The best option for patients with loco-regionally advanced (intermediate to high-risk) disease remains standard chemotherapy. These treatments often become refractory over time with a high recurrence rate of 50–70%
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