结合生物信息数据分析FOXC1在胰腺导管腺癌中的表达及意义  

Analysis of FOXC1 Expression and Its Significance in Pancreatic Ductal Adenocarcinoma Based on Bioinformatic Data

作　　者：曾强 陈林莺[1,2] 李国平 蔡秀虹[1] 罗胜 Zeng Qiang;Chen Linying;Li Guoping(Department of Pathology,the First Affiliated Hospital of Fujian Medical University,Fuzhou 350005,China;Fujian Key Laboratory of Translational Research in Cancer and Neurodegenerative Diseases,,the First Affiliated Hospital of Fujian Medical University,Fuzhou 350005,China)

机构地区：[1]福建医科大学附属第一医院病理科,福州350005 [2]福建省癌症和神经退行性疾病转化研究重点实验室,福州350005

出　　处：《华中科技大学学报（医学版）》2022年第3期309-316,346,共9页Acta Medicinae Universitatis Scientiae et Technologiae Huazhong

基　　金：福建省自然科学基金资助项目(No.2019J01442)。

摘　　要：目的 探究叉头转录因子FOXC1与胰腺导管腺癌(pancreatic ductal adenocarcinoma, PDAC)患者的临床病理特征及预后的关系。方法 利用生物信息数据库探讨FOXC1基因在PDAC中的表达情况以及相关通路分析,同时收集2006~2016年间于福建医科大学附属第一医院行胰腺癌根治术的164例患者资料及手术切除的肿瘤组织,对肿瘤组织切片进行组织病理评估,并行FOXC1免疫组化染色,分析FOXC1蛋白表达与PDAC临床病理特征和预后的关系。结果 多项在线生物信息数据库的分析结果显示,FOXC1在PDAC组织中的表达明显高于正常胰腺组织,FOXC1高表达的患者预后较低表达者更差。在收集的164例PDAC患者中,免疫组化FOXC1高表达者占60.4%(99/164),癌组织中FOXC1高表达与更大的肿瘤直径(P=0.036)、淋巴结受累(P=0.057)有关;FOXC1高表达患者的总生存期(OS)和无疾病进展生存期(DFS)更短(OS:Log-rank=7.620,P=0.006;DFS:Log-rank=13.856,P<0.01),FOXC1表达水平是PDAC患者DFS的独立预后因素(HR=1.778,95%CI=1.220~2.590,P=0.003)。差异基因富集分析显示,FOXC1有关的信号通路主要富集于PI3K/AKT、TP53、细胞粘附等信号通路。结论 FOXC1基因可能与PDAC发生发展相关,其高表达预示着更差的预后,FOXC1有望成为PDAC潜在的生物标记分子。Objective To investigate the relationship between FOXC1 expression and the clinicopathological features as well as prognosis of patients with pancreatic ductal adenocarcinoma(PDAC).Methods Bioinformatic databases were used to explore the FOXC1 expression levels and the related signaling pathways in PDAC.A total of 164 patients who received radical surgery for pancreatic cancer at the First Affiliated Hospital of Fujian Medical University between 2006 and 2016 were collected.The expression of FOXC1 protein was evaluated by immunohistochemical staining.The significance of FOXC1 protein expression in the aspects of clinicopathological features and patient prognosis was also analyzed.Results The expression of FOXC1 in tumor tissues was significantly higher than that in normal pancreatic tissues in PDAC by several online bioinformatic databases.Patients with higher FOXC1 expression had poorer prognosis than those with lower expression.Higher FOXC1 protein expression was observed in 60.4% of cancer tissues(99/164)in PDAC patients, which was positively correlated with tumor size(P=0.036)and lymph node involvement(P=0.057).Patients with higher FOXC1 expression had poorer overall survival(OS)and disease-free survival(DFS)(OS:Log-rank=7.620,P=0.006;DFS:Log-rank=13.856,P<0.01).Multivariate Cox analysis revealed that FOXC1 was an independent prognostic factor for DFS in PDAC patients(HR=1.778,95% CI=1.220-2.590,P=0.003).Furthermore, FOXC1 was highly enriched in PI3 K/AKT,TP53 and cell adhesion signaling pathways.Conclusion FOXC1 may promote tumorigenesis of PDAC and be correlated with poor prognosis of PDAC patients, which plays a role as a potential biomarker for PDAC.

关 键 词：胰腺导管腺癌 FOXC1 临床病理特征 预后 

分 类 号：R392.11[医药卫生—免疫学] R730.7[医药卫生—基础医学]