直肠癌中第10号染色体上缺失与张力蛋白同源的磷酸酯酶基因和Survivin的表达对新辅助放化疗后肿瘤退缩及预后的预测价值

The predictive value of expressions of phosphatase and tensin homologue deleted on chromosome ten and Survivin in rectal cancer for tumor regression and prognosis after neoadjuvant chemoradiotherapy

目的:观察第10号染色体上缺失与张力蛋白同源的磷酸酯酶基因(PTEN)和凋亡抑制蛋白生存素(Survivin)在直肠癌组织中的表达,探讨其对直肠癌新辅助放化疗(nCRT)后肿瘤退缩效果的预测价值及与预后相关性。方法:收集华中科技大学同济医学院附属普爱医院2014年1月至2016年1月行nCRT+全直肠系膜切除术(TME)+辅助化疗(aCT)的直肠癌患者78例,应用免疫组织化学染色法检测直肠癌组织中PTEN、Survivin的表达,应用Spearman等级相关检验分析PTEN和Survivin表达的关系,应用美国肿瘤联合委员会(AJCC)-肿瘤病理评估(TRG)评分系统对放化疗后肿瘤退缩效果进行评价,分析PTEN和Survivin同肿瘤退缩效果之间的关系。采用Kaplan-Meier法分析PTEN、Survivin的表达与无病生存期(DFS)的相关性。结果:免疫组织化学显示PTEN和Survivin的阳性表达率分别为56.4%(44/78)、66.7%(52/78),且两者表达呈负相关(r s=-0.512,P<0.01)。PTEN和Survivin的表达与组织学分型、T分期、淋巴结转移及肿瘤退缩明显相关(χ2=11.031/12.326、8.045/6.205、6.617/5.246、11.204/8.357,P<0.05),而与患者年龄、性别无明显相关(χ2=0.018/0.632、0.143/0.696,P>0.05)。nCRT后肿瘤退缩总有效率为53.8%(42/78),其中PTEN(+)/Survivin(-)组有效率明显高于其他组(χ2=15.031,P<0.05)。Kaplan-Meier生存分析显示,PTEN阳性者的中位DFS(32.0个月)显著高于阴性者(25.0个月)(χ2=4.144,P<0.05)。Survivin阳性者的中位DFS(24.0个月)显著低于阴性者(32.0个月)(χ2=4.126,P<0.05)。结论:PTEN和Survivin在直肠癌组织中的表达呈负相关,两者的表达状态有助于预测nCRT后肿瘤退缩效果和判断预后。

Objective To observe the expression of phosphatase and tensin homologue deleted on chromosome ten(PTEN)and Survivin in rectal cancer and their predictive value in tumor retraction and prognosis after neoadjuvant chemoradiotherapy(nCRT).Methods From January 2014 to January 2016,78 patients with rectal cancer who underwent nCRT+total mesorectal resection(TME)+adjuvant chemotherapy(aCT)were selected.Immunohistochemical staining was used to detect the expression of PTEN and Survivin in rectal cancer tissue.Spearman rank correlation test was used to analyze the relationship between PTEN and Survivin expression.American Joint Committee on cancer(AJCC)-tumor regression grade(TRG)score system was performed to evaluate the effect of tumor withdrawal after nCRT.The relationship between expression of PTEN,Survivin and tumor withdrawal effect was analyzed.The correlation between the expression of PTEN,Survivin and DFS was analyzed by Kaplan-Meier method.Results Immunohistochemistry showed that the positive expression rates of PTEN and Survivin were 56.4%(44/78)and 66.7%(52/78),respectively,and there was a negative correlation between them(rs=-0.512,P<0.01).The expression of PTEN and Survivin was significantly correlated with histological classification,T stage,lymph node metastasis and tumor withdrawal(χ2=11.031/12.326,8.045/6.205,6.617/5.246,11.204/8.357,P<0.05),but not with age and sex(χ2=0.018/0.632,0.143/0.696,P>0.05).The total effective rate of tumor withdrawal after nCRT was 53.8%(42/78),and the effective rate of PTEN(+)/Survivin(-)group was significantly higher than that of other groups(χ2=15.031,P<0.05).Kaplan-Meier survival analysis showed that the median DFS of PTEN positive patients(32.0 months)was significantly higher than that of PTEN negative patients(25.0 months)(χ2=4.144,P<0.05).The median DFS of Survivin positive patients(24.0 months)was significantly lower than that of Survivin negative patients(32.0 months,χ2=4.126,P<0.05).Conclusion There is a negative correlation between the expression of PTEN and Survivin in rectal cancer,and their expression status is helpful to predict the effect of tumor withdrawal and prognosis after nCRT.