联合检测Smac及Caspase9在预测直肠癌术前放化疗敏感性的临床价值  

Clinical significance of joint detection of Smac and Caspase9 protein levels in predicting preoperative chemoradiotherapy sensitivity in patients with rectal cancer

作　　者：熊伟[1] 艾毅钦[1] 汪勇[2] 叶岚[1] 吴星娆[1] 杨军[3] 马丽菊[4] 张静[2] 

机构地区：[1]昆明医科大学第三附属医院(云南省肿瘤医院)放疗中心,云南省昆明市650118 [2]昆明医科大学第一附属医院肿瘤放疗科,云南省昆明市650032 [3]昆明医科大学第一附属医院肿瘤科,云南省昆明市650032 [4]昆明医科大学第一附属医院临床实验中心,云南省昆明市650032

出　　处：《世界华人消化杂志》2015年第25期4041-4050,共10页World Chinese Journal of Digestology

基　　金：云南省教育厅科学研究基金资助项目;No.2011Y186~~

摘　　要：目的:本研究旨在探讨第二线粒体源的半胱天冬酶激活物(second mitochondria-derived activator of Caspase,Smac)及半胱氨酸天冬氨酸蛋白酶9(cysteinyl asparate specific proteinase9,Caspase9)蛋白表达水平与直肠癌术前放化疗后病理反应程度的关系,单独评价及两者联合后评价其表达水平对预测直肠癌术前放化疗敏感性的价值.方法:收集昆明医科大学第一附属医院肿瘤放疗科2008-07/2013-06接受术前放化疗并行手术的直肠腺癌患者43例,免疫组织化学方法检测放化疗前活检标本及手术后切除标本中Smac及Caspase9蛋白的表达水平,分析其放化疗前、后表达水平的变化,以及活检组织中Smac及Caspase9蛋白表达水平与术后病理反应程度的关系.结果:直肠癌术前放化疗后病理反应良好,有效率达72.1%,其中,病理完全缓解率达30.2%.放化疗前、后直肠癌组织中Smac及Caspase9蛋白表达均有差异,放化疗后Smac及Caspase9蛋白的染色得分均下降(P<0.001).放化疗前Caspase9表达阳性的患者(染色得分1-8分)放化疗有效的比例显著增加,差异有统计学意义(P<0.05).当Smac及Caspase9均为阳性时,放化疗有效的比例显著提高(P=0.0002).生存分析显示,放化疗反应结果与患者总生存相关,放化疗有效组的生存时间较放化疗无效组明显延长(P=0.0193).结论:放化疗前活检组织中Caspase9的阳性表达是直肠癌患者对放化疗敏感的标志,联合检测放化疗前Smac及Caspase9的表达可更好地预测直肠癌细胞对放化疗的敏感性.在诸多因素中,直肠癌患者对放化疗的有效性是决定患者预后的重要因素,联合检测活检组织中Smac及Caspase9的表达有可能筛选出对放化疗敏感的患者,从而使其获得更好的预后.AIM： To evaluate the role of second mitochondria- derived activator of Caspase （Smac） and cysteinyl asparate specific proteinase 9 （Caspase9）, alone and in combination, in predicting preoperative chemoradiotherapy sensitivity in patients with rectal carcinoma by investigating the relationship between the expression of Smac and Caspase9 and the pathologic response in patients who have received preoperative chemoradiotherapy. METHODS： The biopsy specimens before chemoradiotherapy and surgical specimens were obtained from 43 cases of rectal adenocarcinoma who received preoperative chemoradiotherapy from July 2008 to June 2013. Immunohistochemical staining was used to test the protein expression levels of Smac and Caspase9, and the relationship between Smac and Caspase9 protein expression levels and postoperative pathological response was analyzed. RESULTS： The effective rate of preoperative chemoradiotherapy was as high as 72.1%, and the pathological complete response rate was 30.2%. The expression of Smac and Caspase9 was altered after chemoradiotherapy （P 〈 0.001 for both）. Their expression levels were significantly downregulated after chemoradiotherapy. The effective rate of preoperative chemoradiotherapy was significantly increased in patients who were positive for Caspase9 protein expression （staining score range, 1 to 8） before chemoradiotherapy （P 〈 0.05）. And the effective rate was further increased when Smac and Caspase9 proteins were both positive （P = 0.0002）. The survival analysis indicated that chemoradiotherapy response was correlated with the overall survival, and the survival was significantly longer in the response arm than in the nonresponse arm （P = 0.0193）. CONCLUSION： The positive expression of Caspase9 protein in biopsy specimens before chemoradiotherapy can be a marker for sensitivity to radiation and chemotherapy in patients with rectal cancer. Joint detection of Smac and Caspase9 proteins can be more reliable in predicting the sensitivity to preoperati

关 键 词：直肠肿瘤 术前放化疗 放疗敏感性 第二线粒体源的半胱天冬酶激活物 半胱氨酸天冬氨酸蛋白酶9 

分 类 号：R735.37[医药卫生—肿瘤]