Saidani Bilel, Boubaker Nouha Setti, Chakroun Marouen, Ayed Haroun, Ksontini Meriem, Naimi Zeineb, Meddeb Khedija, Saadi Ahmed, Rammeh Soumaya, Slama Mohamed Riadh Ben
Urology Department, Charles Nicolle Hospital, Faculty of Medicine, Tunis El Manar University, Tunis, 1006, Tunisia.
Theranostic Biomarkers LR23ES02, Faculty of Medicine of Tunis, University Tunis El Manar, Tunis, 1006, Tunisia.
Mol Biol Rep. 2025 Mar 26;52(1):338. doi: 10.1007/s11033-025-10441-2.
Mutations occurring in the Fibroblast Growth Factor Receptor (FGFR3) gene are thought to be associated with the incidence and prognosis of non-muscle invasive bladder tumors (NMIBC). Yet, their prognostic significance in the Tunisian population remains unclear. Herein, we aim to investigate their prognostic impact in NMIBC in terms of recurrence, progression, and survival.
It is a monocentric retrospective study including 42 NMIBC patients. DNA was isolated from formalin-fixed paraffin-embedded tissue samples. Polymerase Chain Reaction (PCR) followed by Sanger sequencing were performed for a targeted mutations' screening of the hot-spot regions of the FGFR3 gene (exons 7 and 15). Overall survival (OS) and disease-specific survival (DSS) were estimated by the Kaplan-Meier method and the corresponding curves were compared using log-rank test. Sequencing analysis revealed 15 different mutations in FGFR3 gene across 26 different tumors (68%). Among these, 9 are already reported mutations (S249C, P250R, P250S, H251Q, S249S, S249Y, S249A, T264T, Thr651) and, interestingly, 6 are new variants (P250A, H251L, A257S, P253P, I254V, R618S). FGFR3-mutated NMIBC and wild-type FGFR3 tumors were comparable in terms of clinical and endoscopic presentation. The presence of FGFR3 mutations was not statistically correlated to a decrease in OS and DSS. The main factors correlated with their presence were the solid appearance of the tumor (p = 0.04), the presence of tumor calcifications (p = 0.04), and tumor stage (p = 0.04).
FGFR3 mutations were common in our series. These variations seem to be a favorable prognostic factor for NMIBC in our population.
成纤维细胞生长因子受体（FGFR3）基因发生的突变被认为与非肌层浸润性膀胱肿瘤（NMIBC）的发生率和预后相关。然而，其在突尼斯人群中的预后意义仍不明确。在此，我们旨在从复发、进展和生存方面研究其在NMIBC中的预后影响。
这是一项单中心回顾性研究，纳入了42例NMIBC患者。从福尔马林固定石蜡包埋的组织样本中提取DNA。进行聚合酶链反应（PCR），随后进行桑格测序，以对FGFR3基因的热点区域（外显子7和15）进行靶向突变筛查。采用Kaplan-Meier法估计总生存期（OS）和疾病特异性生存期（DSS），并使用对数秩检验比较相应曲线。测序分析在26个不同肿瘤（68%）中发现了FGFR3基因的15种不同突变。其中，9种是已报道的突变（S249C、P250R、P250S、H251Q、S249S、S249Y、S249A、T264T、Thr651），有趣的是，6种是新的变异（P250A、H251L、A257S、P253P、I254V、R618S）。FGFR3突变的NMIBC和野生型FGFR3肿瘤在临床和内镜表现方面具有可比性。FGFR3突变的存在与OS和DSS的降低无统计学相关性。与其存在相关的主要因素是肿瘤的实性外观（p = 0.04）、肿瘤钙化的存在（p = 0.04）和肿瘤分期（p = 0.04）。
FGFR3突变在我们的研究系列中很常见。这些变异似乎是我们人群中NMIBC的一个有利预后因素。
