ERCC1表达水平与晚期食管癌患者含奈达铂方案化疗疗效相关性研究（毕业设计-肿瘤学专业）.doc

目 录英文缩略语………………………………………………………………5 中文摘要…………………………………………………………………6 英文摘要…………………………………………………………………8 前言………………………………………………………………………10 材料与方法………………………………………………………………11 结果………………………………………………………………………17 讨论………………………………………………………………………21 结论………………………………………………………………………29 局限性……………………………………………………………………29 总结展望…………………………………………………………………29 参考文献…………………………………………………………………32 附录………………………………………………………………………37 致谢………………………………………………………………………38 综述………………………………………………………………………39 1 中英文缩略词表英文缩略词 英文全称 中文名称 ERCC1 excision repair cross 核苷酸切除修复交叉互补基因1complementation group 1Karnofsky performancestatusKPS KPS行为状态评分RECIST Response Evaluation 实体瘤疗效评价标准Criteria in Solid Tumorscomplete responsepartial responsestable diseaseCRPR完全缓解部分缓解稳定SDPD progressive diseasenucleotide excision repairno progress free survivaltime进展NERPFS核苷酸切除修复无进展生存时间NDP5-FuDCRnedaplatin 奈达铂fluorouracil 氟尿嘧啶疾病控制率disease control rate2 ERCC1表达水平与晚期食管癌患者含奈达铂方案化疗疗效相关性研究中文摘要[目 的] 相关研究表明，核苷酸切除修复交叉互补基因1（excision repaircross-complementation group 1,ERCC1）在一些常见实体瘤（如胃癌、非小细胞肺癌）中的表达与其铂类药物化疗疗效相关，ERCC1表达可能成为预测铂类药物化疗疗效的指标之一。

目前顺铂联合氟尿嘧啶为晚期食管癌最常用的化疗方案之一，但第二代铂类药物奈达铂由于其较小的肾毒性及消化道反应，现正广泛应用于食管癌化疗本研究通过检测晚期食管癌患者病理组织中ERCC1表达水平，并结合其他临床病理特征分析其与奈达铂化疗后疾病控制率、无进展生存时间之间的关系，探讨晚期食管癌患者组织中切除修复交叉互补基因 1(ERCC1)与含奈达铂联合化疗疗效的关系，为晚期食管癌患者选择化疗药物提供一定的依据[方 法] 回顾性收集安徽省立医院2009年12月～2010年12月收治的Ⅳ期食管癌患者共 102 例入组，予以奈达铂联合氟尿嘧啶方案化疗，同时进行疾病控制率及无进展生存期疗效评估最终有84例患者按规定完成试验并进行数据分析全部数据采用 SPSS 17.0 软件包进行统计学分析，P8者（+++）3例；男74例（88.1%），女10例（11.9%），年龄≥60 岁 47 例（56.0%），＜60 岁 37 例(44.0%)所有患者均具备明确术后病理诊断，病理类型全部为鳞状细胞癌，其中高分化 19 例(22.4%)，中低分化 65 例(77.6%)；KPS 行为状态评分为 90 分 57 例(67.9%)，80 分 22 例(26.1%),70分5例(6.0%)。

在单因素分析中，疾病控制率与ERCC1表达强度及肿3 瘤细胞分化程度相关，无进展生存时间与 ERCC1 表达强度及肿瘤细胞分化程度相关在多因素分析中，近期缓解率与无进展生存期均同样与 ERCC1 表达强度及肿瘤细胞分化程度相关[结 论] 84例晚期食管癌患者在应用奈达铂为基础的联合化疗时，ERCC1表达阴性（＜4）及弱阳性患者（4～5）相对于强阳性患者（≥5）疾病控制率更高，无进展生存时间更长，故此类患者更加适合奈达铂用药；肿瘤细胞高分化患者疾病控制率及无进展生存时间显著优于中低分化患者，此类患者预后相对较好[关键词] ERCC1 奈达铂 免疫组化 晚期食管癌4 A Study on the Relationship between the ERCC1 Expressionand the Effect of Nedaplatin Treating AdvancedEsophageal CancerAbstractObjective:Many studies show that the ERCC1(excision repair cross-complementationgroup 1) gene expression in the tissues of esophageal cancer are associated with theeffect of platinum-based treatment on some solid tumors,such as non-small-cell lungcancer, colorectal cancer and ovarian cancer et al;And they could be predictive factors.Currently, “cisplatin plus fluorouracil” is one of the most frequently used chemotherapyregiments. But due to its smaller nephrotoxicity and gastroenteric reaction,nedaplatin,the second generation of plantinum agent, is being widely used in esophagealcancer chemotherapy at present. Therefore，in this study,we detected the ERCC1 geneexpression of the advcanced esophageal cancer patients treated with nedaplatin-basedchemotherapies, analyzed whether the expression level of ERCC1 and other clincal andpathological factors were related to DCR(disease control rate) and PFS(progression freesurvival).Methods:102 advanced esophageal cancer patients were retrospectively enrolledbetween December 2009 and December 2010 in Anhui provincial hospital. They wereall treated with nedaplatin combined with fluorouracil chemotherapies. The DCR andPFS were assessd,and detected the ERCC1 expression lever in esophageal cancertissues by immunohistochemisty. In the end,84 of 102 patients completed the trials andthe data were available.Statistical anaysis was performed using SPSS statistical softwarepackage 17.0 with P≤0.05 considered as statistically signficant.Univariate ananysis bychi-square test and multivarariate analysis by logistic regression model were used fordisease control rate. PFS curves were calculated accading to Kaplan-Meier method.5 Univariate ananysis by log-rank test and multivarariate analysis by Cox regressionmodel were used for PFS.Results: In all 84 patients, the positive rate of ERCC1 expression was 88.1％(74/84) ,The overall disease control rate was 36.9%（31/84）, while overall disease control rate innegative group of ERCC1 expression was higher than positive group,there were 10cases which expression level were less than 4,49 were ranged from 4 to 5,22 wereranged from 6 to 7,and 3 cases more than 8.There were 74 male and 10 female;47patients were no yunger than 60 years,37 patients were yunger than 60 years; thepathological types of all were squamous cell carcinoma，and of 65 were poor tomoderately differentiated,19 were well differentiated; there were 5 patients’ KPS as 70，22 patients’ KPS as 80 and 57 patients’ KPS as 90; On univariate analysis,ERCC1expression level and tumor differentiation level were related to DCR and PFS. Onmultivariate analysis,ERCC1 expression level and tumor differentiated were also relatedto DCR and PFS.Concolutions:Advanced esophageal cancer patien。