背景:叉头盒蛋白P1(FOXP1)被认为具有致癌和肿瘤抑制特性,取决于肿瘤的异质性。然而,FOXP1在肝内胆管癌(ICC)中的作用尚未见报道.
方法:免疫组化法检测FOXP1在ICC和正常肝组织中的表达。评价FOXP1水平与ICC患者临床病理特征的关系。最后,进行了体外和体内实验以检查FOXP1在ICC细胞中的调节作用。
结果:与肿瘤周围组织相比,FOXP1在ICC中显著下调(p<0.01)。分化差的患者FOXP1阳性率明显降低,淋巴结转移,侵入周围器官,和晚期(p<0.05)。值得注意的是,FOXP1阳性患者的预后(总生存期)优于FOXP1阴性患者(p<0.05),正如Kaplan-Meier生存分析所揭示的。此外,Cox多因素分析显示,FOXP1表达阴性,先进的TNM阶段,入侵,淋巴结转移是ICC患者预后的独立危险因素。最后,过表达FOXP1抑制细胞增殖,迁移,和ICC细胞的侵袭和促进凋亡,而FOXP1的敲除具有相反的作用。
结论:我们的研究结果表明,FOXP1可能是ICC的一种新的预后预测因子,也可能是一种有助于癌症治疗的肿瘤抑制因子。
BACKGROUND: Forkhead-box protein P1 (FOXP1) has been proposed to have both oncogenic and tumor-suppressive properties, depending on tumor heterogeneity. However, the role of FOXP1 in intrahepatic cholangiocarcinoma (ICC) has not been previously reported.
METHODS: Immunohistochemistry was performed to detect FOXP1 expression in ICC and normal liver tissues. The relationship between FOXP1 levels and the clinicopathological characteristics of patients with ICC was evaluated. Finally, in vitro and in vivo experiments were conducted to examine the regulatory role of FOXP1 in ICC cells.
RESULTS: FOXP1 was significantly downregulated in the ICC compared to their peritumoral tissues (p < 0.01). The positive rates of FOXP1 were significantly lower in patients with poor differentiation, lymph node metastasis, invasion into surrounding organs, and advanced stages (p < 0.05). Notably, patients with FOXP1 positivity had better outcomes (overall survival) than those with FOXP1 negativity (p < 0.05), as revealed by Kaplan-Meier survival analysis. Moreover, Cox multivariate analysis showed that negative FOXP1 expression, advanced TNM stages, invasion, and lymph node metastasis were independent prognostic risk factors in patients with ICC. Lastly, overexpression of FOXP1 inhibited the proliferation, migration, and invasion of ICC cells and promoted apoptosis, whereas knockdown of FOXP1 had the opposite role.
CONCLUSIONS: Our findings suggest that FOXP1 may serve as a novel outcome predictor for ICC as well as a tumor suppressor that may contribute to cancer treatment.