"叉头盒"P1蛋白在肝内胆管癌中的表达及其与临床病理特征和预后的关系

Clinicopathological and prognostic significance of expression of forkhead box P1 in patients with intrahepatic cholangiocarcinoma

目的研究"叉头盒"P1蛋白(FOXP1)在肝内胆管癌(ICC)中的表达及其与临床病理特征和预后的关系。方法回顾性分析2013年1月1日至2019年12月12日在上海交通大学医学院附属新华医院行根治性切除术的ICC患者的临床资料。共入选ICC患者48例,其中男性24例,女性24例,年龄(59.1±10.1)岁,年龄范围42~83岁。记录患者的年龄、性别、肿瘤大小、分化程度、分期等临床资料。免疫组织化学方法检测FOXP1在ICC癌组织和癌旁组织中的表达。使用Kaplan-Meier方法计算患者存活率并绘制生存曲线。Cox回归模型分析患者预后的影响因素。结果48例ICC患者对应取得40例癌旁组织。FOXP1在ICC癌组织中的阳性表达率明显低于癌旁正常组织[54.2%(26/48)比92.5%(37/40)],差异具有统计学意义(χ2=15.76,P<0.05)。肿瘤分化程度、淋巴结转移、器官侵犯和TNM分期与FOXP1表达情况相关(P<0.05)。共42例患者获得随访,中位随访时间11.5(7.75,19.25)个月。Cox多因素分析显示,周围器官侵犯、淋巴结转移、高TNM分期(Ⅲ期)和FOXP1阴性表达是影响ICC患者总体生存时间的独立危险因素。FOXP1阳性ICC患者的总体生存时间为17.5个月,无复发生存时间为15.5个月,均高于FOXP1阴性者的总体生存时间14.0个月和无复发生存时间11.1个月,差异均具有统计学意义(P<0.05)。结论FOXP1阴性表达与ICC的恶性生物学行为和不良预后相关;FOXP1可能成为ICC诊断或治疗的新靶点。

Objective To study the expression of forkhead box P1(FOXP1)in intrahepatic cholangiocarcinoma(ICC),and its clinicopathological and prognostic significance.Methods The clinical data of ICC patients treated with radical resection at Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine from January 1,2013 to December 12,2019 were retrospectively analysed.Of 48 ICC patients,there were 24 males and 24 females,with age of(59.1±10.1)years old(range 42 to 83 years old).Their clinicopathological data,including age,gender,tumor size,degree of differentiation,and staging were recorded.Immunohistochemical method was used to detect the expression of FOXP1 protein in ICC cancer tissues and the corresponding adjacent normal tissues.Kaplan-Meier method was used to calculate survival rates and to construct survival curves of patients.Cox regression model was used to analyze factors affecting prognosis of patients.Results Forty-eight ICC cancer tissues and 40 corresponding paracancerous tissues were collected.The positive rates of FOXP1 proteins in ICC were significantly lower than the adjacent normal tissues[54.2%(26/48)vs.92.5%(37/40),χ^(2)=15.76,P<0.05].The degrees of tumor differentiation,lymph node metastasis,organ invasion and TNM staging were related to expression of FOXP1(P<0.05).Forty-two patients were followed-up with a median follow-up time of 11.5(7.75,19.25)months.Cox multivariate analysis revealed that invasion to adjacent organs,lymph node metastasis,high TNM staging(stageⅢ)and negative expression of FOXP1 were independent risk factors affecting overall survival of ICC patients.The overall survival and recurrence-free survival of FOXP1-positive ICC patients were 17.5 months and 15.5 months,which were significantly higher than the 14.0 months and 11.1 months,respectively,in FOXP1-negative patients.Conclusion Negative FOXP1 expression was closely correlated with aggressive biological behavior and poor prognosis of ICC.FOXP1 may be used as new diagnostic and therapeutic targets.