胱硫氨酸β-合成酶在食管胃结合部腺癌中的表达及其临床意义

Expression and clinical significance of cysteineβ-synthase in adenocarcinoma of esophagogastric junction

目的 检测胱硫氨酸β-合成酶(CBS)在食管胃结合部腺癌(AEG)中的表达,探讨CBS表达与肿瘤血管新生、临床病理特征及预后的关系。方法 选取经手术切除的243例AEG患者的蜡块标本制作病理芯片,采用免疫组织化学法检测癌组织及配对癌旁正常组织中CBS、血管内皮细胞生长因子(VEGF)及微血管密度(MVD)的表达情况,分析CBS表达水平与VEGF及肿瘤MVD的相关性。探讨CBS表达水平与AEG患者的临床病理特征及预后的关系。结果 CBS在AEG患者的癌组织和配对癌旁正常组织中的阳性表达率分别为66.67%(162/243)和30.45%(74/243),两组比较差异有统计学意义(P<0.001)。CBS表达水平与T分期、淋巴结转移、吸烟史、VEGF表达及MVD均有关(P<0.05),而与患者的年龄、性别、分化程度、TNM分期及饮酒史无关(P>0.05)。CBS低表达患者的中位无病生存时间(DFS)为63个月,显著长于CBS高表达患者的50个月,差异有统计学意义(P=0.0039)。Cox多因素回归分析显示,CBS表达(HR=1.827,95%CI:1.146~2.912,P=0.011)、VEGF表达(HR=2.684,95%CI:1.637~4.401,P<0.001)、MVD(HR=4.064,95%CI:2.419~6.829,P<0.001)及TNM分期(HR=2.354,95%CI:1.523~3.638,P<0.001)是影响AEG患者DFS的独立因素。结论 CBS高表达可能与肿瘤新生血管相关,是AEG预后的不良因素之一,在AEG的诊治中具有潜在应用价值。

Objective To investigate the expression status of cystathionineβ-synthase in adenocarcinoma of esophagogastric junction(AEG)and analyze the relationship between the expression level of CBS and tumor microvascular density(MVD),clinical features and prognosis.Methods A total of 243 patients with AEG who underwent tumor resection in the Fourth Hospital of Hebei Medical University were enrolled.Surgically resected wax specimens were selected to make pathological chips and for immunohistochemistry.Expression levels of CBS,vascular endothelial growth factor(VEGF)and MVD were detected,respectively.The result were used to clarify the relationship between the expression level of CBS and VEGF,tumor MVD.Furthermore,the correlation between CBS and clinical characters and prognosis were discussed.Results The expression level of CBS was 66.67%(162/243)in AEG tissues,and significantly higher than 30.45%(74/234)in adjacent normal tissues with significant statistical difference(P<0.001).The expression level of CBS was related to T stage,lymph node metastasis,smoking history,VEGF and MVD(P<0.05),but not related to age,gender,degree of differentiation,TNM stage and the history of alcohol use(P>0.05).The median disease-free survival(DFS)of patients with low CBS expression was significantly longer than that of patients with high CBS expression with significant statistical difference(63 months vs.50 months,P=0.0039).The result of Cox multiple regression analysis showed that CBS expression(HR=1.827,95%CI:1.146-2.912,P=0.011),VEGF expression(HR=2.684,95%CI:1.637-4.401,P<0.001),MVD(HR=4.064,95%CI:2.419-6.829,P<0.001)and TNM staging(HR=2.354,95%CI:1.523-3.638,P<0.001)were independent factors affecting DFS in AEG patients.Conclusion High expression of CBS may be related to tumor neovascularization,which is one of the prognostic factors of AEG and has potential application value in the diagnosis and treatment of AEG.