食管癌患者ERCC1和BRCA1的表达水平与5-氟尿嘧啶疗效的关系  

Relationship between Expression Levels of ERCC1 and BRCA1 and Therapeutic Effects of 5-fluorouracil in Patients with Esophageal Cancer

作　　者：钟俊勇[1] 杨楚钦[1] 廖志平[1] 吴志海[1] 郭予武[1] Zhong Junyong;Yang Chuqin;Liao Zhiping;Wu Zhihai;Guo Yuwu(Longgang Central Hospital of Shenzhen,Shenzhen,518016)

机构地区：[1]深圳市龙岗中心医院

出　　处：《基因组学与应用生物学》2019年第8期3741-3745,共5页Genomics and Applied Biology

摘　　要：为了揭示食管癌患者切除修复交叉互补-1 (excision repair cross-complementing-1, ERCC1)和乳腺癌易感基因I (Breast cancer susceptibility gene I, BRCA1)的表达水平与5-氟尿嘧啶为基础的化疗效果、病理反应及预后的相关性。本研究检测了接受5-氟尿嘧啶为基础联合多西他赛治疗的晚期食管鳞状细胞癌(esophageal squamous cell carcinoma, ESCC)患者的ERCC1和BRCA1表达。研究显示,5-氟尿嘧啶为基础联合多西他赛治疗的有效率为36.0%,病理反应率为42.0%。免疫染色评分显示,在病例分级为0/1级的患者中,ERCC1主要为高表达,与2/3级差异显著(p=0.023)。此外,大多数病例分级为0/1级的患者中BRCA1为低表达,而在2/3级的患者中高表达,两组间差异显著(p=0.026)。多因素Logistic回归分析显示,完全缓解/部分缓解(p=0.035)、ERCC1低表达(p=0.009)和BRCA1高表达(p=0.018)与病理反应显著正相关。ERCC1低表达和BRCA1高表达的2和3级肿瘤病理反应发生率为87.5%,而ERCC1高表达和BRCA1低表达的2级和3级病理反应发生率仅为18.8%。ERCC1低表达的患者的2年无复发生存率为81.8%(9/11),而ERCC1高表达为38.5%(15/39),差异有统计学意义(χ~2=6.462;p=0.011)。本研究结论表明ERCC1和BRCA是晚期ESCC患者5-氟尿嘧啶为基础化疗疗效、病理反应和生存相关的敏感生物标志物。To reveal the correlation between the expression levels of excision repair cross-complementing-1(ERCC1) and breast cancer susceptibility gene I(BRCA1) and chemotherapy effect, pathological response and prognosis in patients with esophageal cancer treated by 5-fluorouracil-based chemotherapy, this study examined the expression of ERCC1 and BRCA1 in patients with advanced esophageal squamous cell carcinoma(ESCC)treated with 5-fluorouracil and docetaxel. Studies have shown that the effective rate of 5-fluorouracil-based combined with docetaxel was 36.0%, and the pathological response rate was 42.0%. The immunostaining score showed that ERCC1 was mainly highly expressed in patients with a grade of 0/1, which was significantly different from grade 2/3(p=0.023). In addition, BRCA1 was lowly expressed in most patients with grade 0/1, but was highly expressed in grade 2/3 patients, with significant differences between the two groups(p=0.026). Multivariate logistic regression analysis showed that complete response/partial remission(p=0.035), low expression of ERCC1(p=0.009),and high expression of BRCA1(p=0.018) were significantly positively correlated with pathological response. The incidence of pathological reactions of grade 2 and 3 patients with low expression of ERCC1 and high expression of BRCA1 was 87.5%, while the grade 2 and 3 patients with high expression of ERCC1 and low expression of BRCA1 was only 18.8%. The 2-year recurrence-free survival rate of patients with low expression of ERCC1 was81.8%(9/11), while the high expression of ERCC1 was 38.5%(15/39). The difference was statistically significant(χ~2=6.462;p=0.011). The conclusion of this study indicated that that ERCC1 and BRCA should be sensitive biomarkers related to chemotherapy efficacy, pathological response and survival in patients with advanced ESCC.

关 键 词：食管鳞状细胞癌 病理反应 ERCC1 BRCA1 5-氟尿嘧啶 

分 类 号：R73[医药卫生—肿瘤]