临床肿瘤学杂志

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ERCC1和RRM1蛋白表达与局部晚期宫颈癌含奈达铂同步放化疗疗效的关系

付娟,张爱云,罗爱华,欧宝权,尹宜发   

  1. 三峡大学第二人民医院暨宜昌市第二人民医院肿瘤放化疗科
  • 收稿日期:2015-03-19 修回日期:2015-04-07 出版日期:2015-05-31 发布日期:2015-05-31
  • 通讯作者: 尹宜发

Combined analysis of protein expression of ERCC1 and RRM1 to predict prognosis and curative effect in patients with locally advanced cervical cancer receiving nedaplatin-based concurrent chemoradiotherapy

FU Juan, ZHANG Aiyun, LUO Aihua, OU Baoquan, YIN Yifa.   

  1. Yichang Second People's Hospital, the Second People's Hospital of Three Gorges University
  • Received:2015-03-19 Revised:2015-04-07 Online:2015-05-31 Published:2015-05-31
  • Contact: YIN Yifa

摘要: 目的 探讨核苷酸切除修复交叉互补基因1(ERCC1)和核苷酸还原酶M1亚基(RRM1)的表达与局部晚期宫颈癌含奈达铂同步放化疗疗效的关系。方法 回顾性分析我院2009年2月至2012年11月接受含奈达铂同步放化疗方案治疗的宫颈癌患者72例,根据疗效分为治疗敏感组和治疗抵抗组。采用免疫组织化学法检测治疗前活检组织中ERCC1、RRM1的表达情况,分析两者表达与临床病理参数、疗效及预后的关系,并采用受试者工作特征曲线(ROC)评价ERCC1、RRM1水平在局部晚期宫颈癌含奈达铂同步放化疗疗效预测中的价值。结果 宫颈癌组织中ERCC1、RRM1均呈高表达,ERCC1、RRM1的高表达率分别为54.2%和59.7%,高于正常组织的35.9%和37.5%,差异有统计学意义(P<0.05);治疗敏感组的ERCC1、RRM1高表达率分别为42.9%和47.6%,低于治疗抵抗组的70.0%和76.7%,差异有统计学意义(P<0.05),且ERCC1及RRM1预测宫颈癌放化疗疗效的曲线下面积(AUC)、灵敏度和特异度分别为0.915、92.1%、86.2%和0.944、87.3%、91.0%;ERCC1表达与FIGO分期、分化程度及盆腔淋巴结肿大有关,RRM1表达与分化程度、盆腔淋巴结肿大有关,以上差异均有统计学意义(P<0.05);ERCC1高表达者的中位无进展生存期为27.5个月,与低表达者的28.6个月比较,差异无统计学意义(P>0.05);RRM1高表达者的中位无进展生存期为20.0个月,低于低表达者的37.5个月(P<0.05)。
结论 宫颈癌组织中ERCC1、RRM1呈高表达,且两者表达水平均与疗效、分化程度及盆腔淋巴结肿大有关,RRM1表达亦与预后有关,两者可用于局部晚期宫颈癌含奈达铂同步放化疗疗效的预测。

Abstract: Objective To explore the protein expression of nucleotide excision repair cross complementing gene 1 (ERCC1) and ribonucleotide reductase subunit M1 (RRM1) and their roles in predicting prognosis and curative effect in patients with locally advanced cervical cancer receiving nedaplatinbased concurrent chemoradiotherapy (CCRT). Methods In a retrospective analysis, 72 patients with cervical cancer in our hospital from February 2009 to November 2012 receiving nedaplatin-based CCRT were enrolled. According to the effect of CCRT, the patients were assigned into sensitive group and resistance group. The protein expressions of ERCC1 and RRM1 were detected by immunohistochemistry method in the biopsy tissues before treatment. The impact of expression of proteins on the prognosis and therapeutic effect, and their correlations with clinicopathological features were investigated further. The predictive value of ERCC1 and RRM1 on the curative effect of nedaplatinbased CCRT was investigated by receiver operating characteristic curve (ROC) analysis. Results The RRM1 and ERCC1 expressions in carcinoma tissues were higher than those in paracarcinoma tissues (P<0.05). The 54.2% and 59.7% of patients with tumors had high expressions of ERCC1 and RRM1, respectively. In sensitive group, the highexpression rates of ERCC1 and RRM1 were 42.9% and 47.6%, lower than 70.0% and 76.7% in resistance group with significant difference(P<0.05). The AUC, sensitivity and specificity of ERCC1 and RRM1 in predicting the curative effect of nedaplatin-based CCRT were 0.915 and 0.944, 92.1% and 87.3%, and 86.2% and 91.0%, respectively. Expression of ERCC1 was related with FIGO staging, differentiation and pelvic lymph node swelling, and expression of RRM1 was related with the degree of differentiation and pelvic lymph node swelling (P<0.05). The median progression free survival (PFS) of patients with high ERCC1 expression was 27.5 months, similar with the 286 months in patients with low ERCC1 expression. The median PFS was 200 months in patients with high RRM1 expression, lower than 37.5 months in patients with low RRM1 expression(P<0.05).
Conclusion There are higher expression levels of ERCC1 and RRM1 in cervical carcinoma tissues. Both the expression levels of two proteins are related with the curative effect, the degree of differentiation and pelvic lymph node swelling. Both levels of ERCC1 and RRM1 can be used for the prediction of curative effect in locally advanced cervical cancer receiving nedaplatinbased concurrent chemoradiotherapy.

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