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Signal transducer and activator of transcription (STAT) proteins are cytoplasmic transcription factors known to play key roles in numerous physiological and pathological processes, from pathogen response to cancer modulation. However, the roles of some STAT family members, particularly STAT1 and STAT4, in the initiation and progression of bladder cancer (BC) have not been comprehensively studied. The present study investigated the expression pattern of STAT1 and STAT4 in the prognosis and survival of BC taking advantage of patients' specimens and cell lines. In our cohort, high mRNA expression of STAT1 was significantly associated with tumor invasiveness, recurrence and progression, and was shown to increase according to tumor stage in BC cell lines. However, it did not affect patient survival. By contrast, STAT4 exhibited its highest expression in early-stage tumors, without a significant link to the tumor stage. Moreover, it was found that increased STAT4 mRNA expression was associated with improved disease-free survival and overall survival in our cohort. Collectively, these findings suggest that STAT1 and STAT4 could be promising prognostic markers to enhance BC management., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2025 El Ahanidi et al.)

The transcription factor TWIST1 is a major regulator of Epithelial-Mesenchymal Transition, enhancing cancer cell mobility and invasive potential. Overexpression of TWIST1 is associated with tumor progression and poor prognosis. In our study, we explored the role of TWIST1 as both a prognostic biomarker and a therapeutic target in bladder cancer (BC), as well as the relationship between its promoter methylation and mRNA expression in bladder cancer patients. In cohort of 66 bladder cancer patients, we explored TWIST1 expression levels in tumor samples through RT-qPCR analysis; Our findings revealed a significant correlation between high TWIST1 expression levels and advanced bladder tumor stages, grades, and progression; suggesting its association with aggressive BC phenotypes. Importantly, patients with low TWIST1 expression exhibited significantly prolonged disease-free survival (DFS), indicating its potential as a prognostic marker for stratification and as a therapeutic target in advanced BC. In contrast, there was no direct correlation between TWIST1 promoter methylation status and TWIST1 expression levels in BC tumors. In summary, TWIST1 expression could play an important role as a molecular marker for BC patients' prognosis and overall survival prediction. Moreover, our results suggest that TWIST1 promoter methylation doesn't affect the gene expression in BC. Furthermore, understanding the molecular mechanisms driving TWIST1 dysregulation may uncover novel therapeutic targets to improve the management of BC., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2025. Published by Elsevier Inc.)