碱性“彗星”法检测肺癌初始放射损伤与临床疗效的相关性  

Correlation of initial DNA damage detected by alkaline comet assay and clinical endpoints in lung cancer patients

作　　者：吕纪马[1] 王绿化[1] 杨伟志[1] 张晓华[1] 王冕荣[1] 阎洁[1] 

机构地区：[1]中国医学科学院北京协和医科大学肿瘤医院,100021

出　　处：《中国肺癌杂志》2006年第2期187-191,共5页Chinese Journal of Lung Cancer

摘　　要：背景与目的肺癌细胞具有显著的生物学异质性和内在放射敏感性差异,探求其放射敏感性相关参数以优化治疗计划是亟待解决的问题。“彗星”分析法(cometassay)可以通过荧光显微镜直接定量地检测单个细胞的DNA损伤,具有需要细胞数少、灵敏和快速的优点。临床前的相关研究显示:彗星分析法与经典的克隆形成率分析的结果趋势一致,是一种有潜力的放射敏感性分析法。本研究旨在用碱性彗星法检测31例放射治疗肺癌标本的初始DNA损伤,初步探讨其与疗效的相关性。方法2002年4月至2002年11月,用碱性彗星法检测31例接受放射治疗的肺癌病例在治疗前经支气管镜活检标本的初始DNA损伤,以经本底较正的平均尾力矩(RTM)为评价指标,同时以胸部CT扫描评价局部肿瘤反应率(RR)和肿瘤进展时间(TTP);用SPSS10.0统计软件以曼惠特尼U检验和克鲁斯沃里斯H检验比较不同病理类型、RR和TTP组的中位RTM;计算RTM与RR和TTP的斯皮尔曼等级相关系数。结果不同病理类型组、RR≥50%组和TTP>9个月组中位RTM与对应组相应值间比较均无统计学差异(χ2=0.347,P=0.84;U=63.5,P=0.57;U=71,P=0.057);RTM与RR和TTP的斯皮尔曼相关系数分别为-0.105(P=0.57)和0.38(P=0.035):非小细胞肺癌的RTM与TTP斯皮尔曼相关系数为0.47(P=0.048),而小细胞肺癌为0.043(P=0.89)。结论尽管受取材质量和混杂因素致本底DNA损伤高的影响,碱性彗星法检测的肺癌初始放射损伤(RTM)仍可显示出与非小细胞肺癌局部TTP具有中等强度的正相关性,“彗星”分析法是一种有希望的肺癌细胞放射敏感性分析法,其取材和实验方法有待改进。Background and objective Cells derived from lung cancer are biological heterogeneous and have different intrinsic radiosensitivity, it is a key question for us to investigate radiosensitive parameters for an individualized radiotherapy plan. The comet assay is a sensitive and facilitated method to detect single-cell DNA damage and repair, and the results from it have been proven to be so highly coincident with those from clonogenic assay by cell-line investigations that it has been considered as a promising method in predicting radiosensitivity. The study is designed to evaluate preliminarily the correlation between initial DNA damage detected by alkaline comet assay and the clinical endpoints. Methods Biopsy samples from 31 lung cancer patients by fibrous bronchial endoscopy were detected by alkaline comet assay from April, 2002 to November, 2002. The adjusted tail moment （RvM） was measured and thoracic local-region lesions were measured by computer tomography scan. Response rate （RR） and time to progression （TTP） for the local-region lesions were as clinical endpoints. SPSS 10.0 software was used to compare median RTM of different RR and TTP groups by Mann-Whitney U and Kruskal-Wallis H rank test, the correlations between RTM with RR and TTP were esti- mated by Spearman＇s rank test. Results There were no statistic differences of median RTM among different pathological types with a median RTM of 0. 98, 1. 27 and 1.05 in squamous cell carcinoma group, adenocarcinoma group and small cell lung cancer group, respectively （χ^2 = 0. 347, P=0.84）. Through a median follow-up of 10 months, a median RTM of 1. 08 and 1. 21 for squamous cell carcinoma group and small cell lung cancer group in RR≥50% group was greater than 0.88 and 0.91 in RR〈50% group; median RTM in TTP〉9-month groups stratified according to pathological type was greater than that in TTP≤9-month groups （1.26, 1.38 and 1.39 versus 0.71, 0.48 and 1.03 for squamous cell carcinoma group, adenocarcinoma group and small cell lung canc

关 键 词：“彗星”分析 肺肿瘤 预测试验 放射治疗 

分 类 号：R734.2[医药卫生—肿瘤]