Department of Oral and Maxillofacial-Head Neck Oncology, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
National Clinical Research Center for Oral Diseases,National Center for Stomatology, Shanghai, China.
Oral Dis. 2024 Apr;30(3):1004-1017. doi: 10.1111/odi.14542. Epub 2023 Apr 24.
The fibroblast growth factor receptor (FGFR) members including FGFR1-4 have been identified as promising novel therapeutic targets and prognostic markers in multiple solid tumors. However, the predictive role of the expression of FGFR proteins in oral squamous cell carcinoma (OSCC) requires further exploration.
Immunohistochemical evaluation of FGFR1-4 was performed on 161 paired OSCC samples. The associations of FGFRs with clinicopathologic and prognostic parameters were analyzed. To further assess the contribution of FGFRs to OSCC proliferation, cell lines, and one PDX model was utilized to examine the anti-tumor effect of the pan-FGFR inhibitor AZD4547.
All FGFR members were found to be overexpressed in OSCC tumors when compared to normal tissues, and their expression was significantly associated with poor overall survival and disease-free survival. Multivariate Cox regression analysis revealed high expression of FGFR1 (p = 0.014) and FGFR4 (p = 0.009) were independent prognostic factors and co-overexpression of FGFR1 and FGFR4 with lymph node metastasis increased HR for death (p = 0.02). The pan-FGFR inhibitor AZD4547 showed anti-tumor activity in cell lines and in a patient-derived xenograft of OSCC.
This study highlights the co-overexpression of FGFR1 and FGFR4 as a significantly poor prognosis indicator in OSCC when combined with lymph node metastasis.
成纤维细胞生长因子受体（FGFR）家族成员包括 FGFR1-4，已被确定为多种实体瘤中很有前途的新型治疗靶点和预后标志物。然而，FGFR 蛋白在口腔鳞状细胞癌（OSCC）中的表达的预测作用仍需进一步探索。
对 161 对配对的 OSCC 样本进行 FGFR1-4 的免疫组织化学评估。分析 FGFR 与临床病理和预后参数的关系。为了进一步评估 FGFR 对 OSCC 增殖的贡献，利用细胞系和一个 PDX 模型来检查泛 FGFR 抑制剂 AZD4547 的抗肿瘤作用。
与正常组织相比，所有 FGFR 成员在 OSCC 肿瘤中均过度表达，其表达与总生存率和无病生存率显著相关。多变量 Cox 回归分析显示，FGFR1 高表达（p=0.014）和 FGFR4 高表达（p=0.009）是独立的预后因素，FGFR1 和 FGFR4 的共同过表达与淋巴结转移增加了死亡的 HR（p=0.02）。泛 FGFR 抑制剂 AZD4547 在细胞系和 OSCC 的患者来源异种移植模型中显示出抗肿瘤活性。
本研究强调了 FGFR1 和 FGFR4 的共同过表达与淋巴结转移结合时，是 OSCC 预后不良的显著指标。
