Abstract
6-phosphofructo-2-kinase/fructose-2,6-biphosphatase-3 (PFKFB3) influences cancer progression via participating in tumor aerobic glycolysis. In this study, we aimed to evaluate the prognostic significance of PFKFB3 in bladder cancer (BLCA) patients by analyzing a combination of publicly available databases, clinical patient data, and bladder tumor samples from our hospital. Single-cell and bulk RNA-seq data of bladder cancer, obtained from ENA, GEO, and TCGA databases, were utilized for our analysis. The results indicated that PFKFB3 mRNA expression was markedly elevated in bladder cancer compared to paired normal tissue. Furthermore, BLCA patients with high PFKFB3 expression exhibited a significantly worse prognosis (P < 0.05). To validate these findings, clinical data and immunohistochemistry staining were performed on specimens obtained from 89 BLCA patients who underwent radical cystectomy at either Qingdao University Affiliated Hospital or Peking Union Medical College Hospital. The findings from this verification process confirmed that high expression of PFKFB3 serves as a biomarker for predicting worse prognosis in BLCA patients (OR: 2.462, 95 % CI: 1.202-5.042, P = 0.012). To facilitate clinical application, we developed a nomogram based on four variables, including PFKFB3 expression, to predict the survival of BLCA patients. Importantly, this nomogram demonstrated a low mean prediction error of 0.03. Taken together, our findings suggest that PFKFB3 has the potential to serve as both a prognostic biomarker and a therapeutic target for BLCA patients.