Evaluation of Fibroblast Growth Factor Receptor 3 (FGFR3) and Tumor Protein P53 (TP53) as Independent Prognostic Biomarkers in High-Grade Non-muscle Invasive Bladder Cancer

评估成纤维细胞生长因子受体3 (FGFR3) 和肿瘤蛋白P53 (TP53) 作为高级别非肌层浸润性膀胱癌独立预后生物标志物的价值

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Abstract

Introduction Bladder cancer is a significant health issue with an increased recurrence and progression rate, requiring invasive follow-up, which shows a poor prognosis. In addition, the prognostic role of mutant fibroblast growth factor receptor 3 (FGFR3) and tumor protein P53 (TP53) is controversial; therefore, we investigated the methylation status and their altered gene expression in low- and high-grade non-muscle-invasive bladder cancer (NMIBC) subjects. Materials and methods This case-control study was conducted between 2020 and 2023, in which n = 115 tumor tissues (NMIBC n = 85) and (controls n = 30) were examined for FGFR3 and FGFR promoter methylation and expression using methylation-specific PCR (MSP) and real-time PCR. The multivariate regression analysis and Kaplan-Meier (KM) plots were used to establish the association of FGFR3 and TP53 with clinicopathological features and survival outcomes of NMIBC patients. Results High-grade NMIBC tumors showed substantial methylation patterns, with TP53 hypomethylated (p = 0.034) and FGFR3 hypermethylated (p = 0.046), as well as significant mRNA expression of Tp53 and FGFR3 (p = 0.001). The multivariate analysis shows FGFR3 and Tp53 were associated with recurrence-free survival with sensitivity (p = 0.045 (78%); 0.034 (70.7%)) and progression-free survival (p = 0.022(61.5%); 0.038 (69.2%)).  Conclusion The findings of this investigation indicate that FGFR3 hypermethylation and TP53 hypomethylation are independent prognostic indicators that aid in the evaluation of disease outcomes in high-grade NMIBC tumors.

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