目的 分析溶质载体家族4的硼酸钠转运蛋白成员11 (SLC4A11)和肿瘤蛋白P53在胃癌组织中的蛋白质表达及临床意义.方法 纳入2004年3月至2009年12月在南通大学附属医院普外科行手术治疗的415例胃癌患者,收集其病历资料和胃癌组织标本.另纳入同期在南通大学附属医院普外科行手术治疗的64例非胃癌的胃部疾病患者,收集其病历资料和胃癌前病变组织.将收取的组织制作成组织芯片,采用免疫组织化学染色法检测组织芯片中SLC4A11和肿瘤蛋白P53的蛋白质表达,分析两者与临床病理特征和预后的关系.统计学方法采用卡方检验、单因素和多因素分析.结果 胃癌组织中SLC4A11和肿瘤蛋白P53的蛋白质表达阳性率分别为48.19%(200/415)和34.94%(145/415),分别高于胃癌前病变组织中的17.19%(11/64)和6.25%(4/64),差异均有统计学意义(x2=24.150、59.345,P均<0.01).SLC4A11蛋白质表达与人类表皮生长因子受体2(Her2)、浸润深度、远处转移和TNM分期相关,差异均有统计学意义(x2=28.056、11.300、8.880、24.943,P均<0.05);肿瘤蛋白P53的蛋白质表达与浸润深度、淋巴结转移、远处转移、TNM分期和术前癌胚抗原水平相关,差异均有统计学意义(x2=12.333、7.875、9.347、20.307、10.678,P均<0.05).SLC4A11和肿瘤蛋白P53的蛋白质表达呈正相关(x2=6.237,P=0.013).单因素分析显示,SLC4A11蛋白质表达阳性、肿瘤蛋白P53蛋白质表达阳性、SLC4A11和肿瘤蛋白P53的蛋白质表达双阳性、Her2表达阳性、术前癌胚抗原水平和术前癌抗原19-9水平均与胃癌患者的不良预后相关[风险比(HR)=1.947、1.459、1.797、1.419、2.221、1.908,P均<0.05];多因素分析显示,SLC4A 11蛋白质表达阳性和TNM分期是判断胃癌患者预后的独立指标(HR=1.954、1.468,P均<0.05).结论 SLC4A11和肿瘤蛋白P53的蛋白质高表达与胃癌的发生、发展相关,联合检测两者的变化将有助于胃癌的早期诊断,以及评估胃癌患者的预后.
Objective To explore the expression and clinical significance of sodium borate transporter member 11 of solute carrier family 4 (SLC4A11) and tumor protein P53 (TP53) proteins in gastric cancer (GC).Methods From March 2004 to December 2009,a total of 415 patients with GC,who received operation at Department of General Surgery of Affiliated Hospital of Nantong University,were enrolled.The clinical data and gastric tissues samples of them were collected.At same period,64 patients with non-malignant gastric diseases,who underwent surgery at Department of General Surgery of Affiliated Hospital of Nantong University,were also recruited.The clinical data and gastric precancerous tissues were also collected.The tissues were maken into tissue microarray (TMA).The expression of SLC4A11 and TP53 protein in tissue microarrays was detected by immunohistochemical staining.The relationship between the two proteins and clinicopathological parameters and prognosis of patients were analyzed.Chi square test,and univariate and multivariate analyses were used for statistical analysis.Results The positive rates of protein expression of SLC4A11 and TP53 in GC tissues were 48.19% (200/415) and 34.94% (145/415),respectively,which were higher than 17.19% (11/64) and 6.25% (4/64) in gastric precancerous lesions,respectively,and the differences were statistically significant (x2 =24.150 and 59.345;both P<0.01).The results of statistical analysis showed that the expression of SLC4A11 was correlated with human epidermal growth factor receptor 2(Her2) levels,depth of invasion,distant metastasis and TNM staging (x2 =28.056,11.300,8.880,24.943;all P<0.05).Meanwhile,the expression of TP53 was related with depth of invasion,lymph node metastasis,distant metastasis,TNM staging and preoperative carcinoembryonic antigen (CEA;x2=12.333,7.875,9.347,20.307,10.678;all P<0.05).The expression of TP53 was significantly positive correlated with SLC4A11 expression (x2 =6.237,P=0.013).The results of univariate analysis showed that SLC4A11,TP53,SLC4A11+/TP53+,Her2,preoperative CEA and cancer antigen 19-9 (CA19-9) levels were correlated with the poor prognosis of GC patients (hazard ratio (HR)=1.947,1.459,1.797,1.419,2.221,1.908;all P<0.05),while the results of multivariate analysis indicated that positive SLC4A11 and TNM staging were the independent parameters for judging the prognosis of patients with GC (HR =1.954,1.468,both P<0.05).Conclusions The high expression of SLC4A11 and TP53 is related to the occurrence and development of GC.Combined detection of their changes will contribute to the early diagnosis and prognostic evaluation of patients with GC.