外周血ERCC1表达及基因多态性与局部晚期直肠癌新辅助放化疗疗效的关系

Relationship between peripheral blood ERCC1 expression and gene polymorphism and neoadjuvant chemoradiotherapy for locally advanced rectal cancer

目的观察外周血切除修复交叉互补基因(ERCC1)表达水平及基因多态性对局部晚期直肠癌患者术前新辅助放化疗/化疗疗效的影响。方法选取2017年3月~2020年5月在河北北方学院附属第一医院94例术前接受CapeOX方案化疗或新辅助放化疗的中低位直肠癌患者。治疗前留取患者外周血样本,实时荧光PCR检测其mRNA表达水平,PCR-LDR进行基因分型,分析ERCC1mRNA表达量及基因多态性与疗效的关系。结果肿瘤组织中ERCC1 mRNA相对表达量高于血液中的表达量,肿瘤组织与外周血中ERCC1的表达呈正相关(r=0.619,P=0.004)。肿瘤组织与外周血ERCC1基因型完全一致。以外周血表达量的中位数0.25将患者分为高表达组和低表达组,采用新辅助放化疗的ERCC1低表达组有效率高于高表达组,但组间差异无统计学意义(P>0.05),采用新辅助化疗的ERCC1低表达组有效率高于高表达组,组间差异有统计学意义(P<0.05)。新辅助放化疗、新辅助化疗不同基因型疗效差异无统计学意义(P>0.05)。结论晚期直肠癌外周血ERCC1mRNA高表达患者CapeOX新辅助化疗疗效不佳,ERCC1基因多态性与含奥沙利铂的新辅助放化疗/化疗敏感性无明显相关性,检测外周血ERCC1mRNA有助于指导晚期结直肠癌患者个体化治疗。

Objective To observe the effect of excision repair crosscomplementing 1(ERCC1)expression level and gene polymorphism in peripheral blood on the efficacy of preoperative neoadjuvant chemoradiotherapy/chemotherapy in patients with locally advanced rectal cancer.Methods 94 patients with middle and low rectal cancer who received capeox chemotherapy or neoadjuvant chemoradiotherapy before operation were studied.Tumor tissue and peripheral blood samples were taken before treatment.The mRNA expression level was detected by real-time fluorescent PCR.PCR-LDR was genotyped to analyze the relationship between ERCC1 mRNA expression and gene polymorphism and curative effect.Results The relative expression of ERCC1 mRNA in tumor tissue was higher than that in blood.There was a positive correlation between the expression of ERCC1 in tumor tissue and peripheral blood,r=0.05619,P=0.004。The ERCC1 genotype of tumor tissue was completely consistent with that of peripheral blood.The median of peripheral blood expression was 0.25.The patients were divided into high expression group and low expression group.The effective rate of ERCC1 low expression group with neoadjuvant radiotherapy and chemotherapy was higher than that of high expression group,but there was no significant difference between the groups(P>0.05).The effective rate of ERCC1 low expression group with neoadjuvant chemotherapy was higher than that of high expression group(P<0.05).There was no significant difference between different genotypes of neoadjuvant radiotherapy and chemotherapy and neoadjuvant chemotherapy(P>0.05).Conclusion The efficacy of capeox neoadjuvant chemotherapy is poor in patients with high expression of ERCC1 mRNA in peripheral blood of advanced colorectal cancer.There is no significant correlation between ERCC1 gene polymorphism and the sensitivity of neoadjuvant chemoradiotherapy/chemotherapy containing oxaliplatin.The detection of ERCC1 mRNA in peripheral blood is helpful to guide the individualized treatment of patients with advanced colorectal cancer.