B细胞易位基因2在食管鳞癌组织中的表达及临床意义

目的:探讨B细胞易位基因2（BTG2）在食管鳞状细胞癌（ESCC）组织中的表达及临床意义。方法:分析癌症基因组图谱（TCGA）数据库中BTG2 mRNA在ESCC组织及癌旁组织中的表达，受试者工作特征（ROC）曲线分析BTG2 mRNA表达量在预测ESCC患者疾病状态和放疗敏感性中的诊断价值；免疫组织化学检测我院184例ESCC患者癌组织标本BTG2蛋白表达，其中包括55例行根治性放疗术的ESCC患者，50例正常黏膜组织作为对照。分析BTG2蛋白表达情况与ESCC临床特征的关系。结果:与对照组比较，BTG2 mRNA在ESCC组织中表达下降（5.08±1.06 vs 5.91±1.29,t=2.387，P=0.019），与放疗敏感组患者比较，BTG2 mRNA在放疗抵抗的ESCC患者癌组织中表达下降（3.82±0.97 vs 5.44±0.73，t=4.935，P＜0.001），ROC结果显示BTG2 mRNA在鉴别放疗敏感与放疗抵抗患者时特异性为95.65%，敏感性为75%（AUC=0.902，P＜0.001）；免疫组织化学结果显示ESCC组织中BTG2阳性表达（103/184）低于正常黏膜组织（42/50），差异有统计学意义（χ2=13.10，P＜0.001）；BTG2表达在放疗敏感和放疗抵抗组织中的阳性表达率分别为57.9%（22/38）和23.5%（4/17），差异有统计学意义（χ2=5.565，P=0.018）；ESCC患者BTG2蛋白表达差异在不同性别、年龄、T分期及M分期中无统计学差异（P＞0.05），与N分期（χ2=4.134，P=0.042）及临床分期（χ2=5.303，P=0.021）相关；单因素分析结果显示，肿瘤分级（HR=0.500，95%CI:0.317～0.790，P=0.003）、N分期（HR=0.275，95%CI:0.157～0.479，P=0.000）、M分期（HR=0.317，95%CI:0.151～0.665，P=0.002）、临床分期（HR=0.269，95%CI:0.167～0.434，P=0.000）及BTG2表达（HR=1.956，95%CI:1.242～3.079，P=0.003）与ESCC患者总生存（OS）有关；多因素分析结果显示，肿瘤分级（HR=0.613，95%CI:0.381～0.987，P=0.044）、N分期（HR=0.507，95%CI:0.259～0.991，P=0.047）、临床分期（HR=0.504，95%CI:0.278～0.916，P=0.025）及BTG2表达（HR=1.608，95%CI:1.011～2.558，P=0.045）影响ESCC患者的OS。结论:BTG2具有作为预测ESCC进展及放疗敏感性生物标记物的潜在价值，并且是影响ESCC患者总生存率的独立预后因素。

Expression and clinical significance of B cell translocation gene 2 in esophageal squamous cell carcinoma tissues

Objective:To study the expression and clinical significance of B cell translocation gene 2(BTG2)in esophageal squamous cell carcinoma(ESCC).Methods:BTG2 mRNA expression levels were determined by analyzing the RNAseq data from the Cancer Genome Atlas(TCGA)database,and receiver operating characteristic(ROC)curves were used to evaluate the clinical value of BTG2 mRNA in diagnosis of ESCC or radiosensitivity.The protein expression of BTG2 in 184 cases of primary esophageal squamous cell carcinoma were detected by immunohistochemistry,among which 55 patients who received radical radiotherapy diagnosed by ESCC.50 cases of normal esophageal mucosa were used as the controls.The relationship between the expression level of BTG2 and radiotherapy sensitivity and prognosis of ESCC were analyzed.Results:The level of BTG2 mRNA was significantly decreased in ESCC patients compared to controls(5.08±1.06 vs 5.91±1.29,t=2.387,P=0.019),and decreased significantly in radiotherapy resistance patients compared to radiotherapy sensitive patients(3.82±0.97 vs 5.44±0.73,t=4.935,P<0.001).The area under the ROC curve(AUC)for BTG2 in predicting radiotherapy resistance patients from radiotherapy sensitive patients was 0.902,with the sensibility at 75%and the specificity at 95.65%.The positive expression rate of BTG2 protein in 184 ESCC tissue samples was 56.0%(103/184)and 84.0%(42/50)in normal esophageal mucosa,respectively.Differences were statistically significant(χ²=13.10,P<0.001).The positive ratios of BTG2 expression in radiotherapy sensitive group and radiotherapy resistance group were 57.9%(22/38)and 23.5%(4/17),respectively.The difference of which was statistically significant(χ²=5.565,P=0.018).There was no significant correlation between the expression level of BTG2 and gender,age,T grading,M grading(P>0.05),but correlated with N stage(χ²=4.134,P=0.042)and clinical staging of ESCC patients(χ²=5.303,P=0.021).Univariate analysis showed that tumor grade(HR=0.500,95%CI:0.317~0.790,P=0.003),N grading(HR=0.275,95%CI:0.157~0.479,P=0.000),M grading(HR=0.317,95%CI:0.151~0.665,P=0.002),clinical staging(HR=0.269,95%CI:0.167~0.434,P=0.000)and BTG2 level(HR=1.956,95%CI:1.242~3.079,P=0.003)were closely related to the prognosis of patients.The multivariate analysis of Cox regression model showed that the tumor grade(HR=0.613,95%CI:0.381~0.987,P=0.044),clinical staging(HR=0.504,95%CI:0.278~0.916,P=0.025),N grading(HR=0.507,95%CI:0.259~0.991,P=0.047)and BTG2 level(HR=1.608,95%CI:1.011~2.558,P=0.045)were the independent risk factors affecting the prognosis of ESCC patients.Conclusion:The downregulation may be used as a molecular marker to identify and predict the progression and radiosensitivity,and may be an independent factor influencing the prognosis of patients with ESCC.