宫颈鳞癌中ERCC1甲基化与顺铂为基础同期放化疗敏感性关系研究
Relationship between excision repair cross-complementation group 1 methylation and sensitivity to cisplatin-based concurrent chemoradiotherapy in cervical squamous cell carcinoma
摘要目的:探讨核苷酸切除修复交叉互补基因1( ERCC1)甲基化状态与宫颈鳞癌患者以顺铂为基础同期放化疗敏感性关系及与临床病理特征的关系。方法采用甲基化特异性PCR法检测20例正常宫颈组织和60例宫颈鳞癌组织中ERCC1基因甲基化状态,宫颈鳞癌患者均接受以顺铂为基础同期放化疗。按照RECIST标准评价疗效,根据疗效结果将CR定为放化疗敏感组, PR+SD+PD为放化疗抗拒组。采用χ2检验比较两组间ERCC1基因甲基化状态差异,采用Logistic多元回归进行多因素分析ERCC1基因甲基化状态与各临床病理特征的关系和放化疗敏感性的相关性。结果宫颈鳞癌组织中 ERCC1甲基化概率为60%,高于正常宫颈组织0%( P=0?000)。多因素分析显示ERCC1甲基化是影响宫颈鳞癌以顺铂为基础的同期放化疗敏感性因素( P=0?022);ERCC1基因甲基化与宫颈鳞癌患者组织学分级具有相关性( P=0?030),与患者年龄、肿瘤大小、淋巴结转移、FIGO分期、治疗前血红蛋白及血小板计数等临床病理特征关系差异均相近( P=0?729、0?707、0?340、0?747、0?073、1?000)。结论 ERCC1基因启动区甲基化状态可能参与宫颈鳞癌的发生发展,可能影响宫颈鳞癌以顺铂为基础同期放化疗敏感性,可能参与了细胞分化过程。
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abstractsObjective To investigate the correlation of the excision repair cross?complementation group 1 ( ERCC1 ) gene methylation status with sensitivity to cisplatin?based concurrent chemoradiotherapy and clinical pathological characteristics in patients with cervical squamous cell carcinoma ( CSCC) . Methods Methylation specific polymerase chain reaction was used to determine the ERCC1 gene methylation status in cervical tissue from 20 healthy people and 60 patients with CSCC. All patients with CSCC were treated with cisplatin?based concurrent chemoradiotherapy. The treatment outcomes were evaluated using the Response Evaluation Criteria in Solid Tumors. Based on the treatment outcomes, patients with a complete response were assigned to chemoradiotherapy?sensitive group, and patients with a partial response, stable disease, or progressive disease were assigned to chemoradiotherapy?resistant group. Comparison of the ERCC1 gene methylation status between the two groups was made by χ2 test, and multivariate logistic regression analysis was used to analyze the relationship of the ERCC1 gene methylation status with various clinical pathological characteristics and sensitivity to chemoradiotherapy. Results The ERCC1 gene methylation rate was significantly higher in cervical tissue with CSCC than in normal cervical tissue ( 60% vs. 0%, P= 0?000 ) . The multivariate analysis showed that ERCC1 gene methylation was an independent influencing factor for sensitivity to cisplatin?based concurrent chemoradiotherapy in CSCC ( P=0?022 );ERCC1 gene methylation was significantly correlated with histological grade of CSCC ( P=0?030);there was no significant relationship of ERCC1 gene methylation with clinical pathological characteristics including age, tumor size, lymph node metastasis, FIGO stage, and pretreatment hemoglobin and platelet count ( P=0?729,0?707,0?340,0?747,0?073,1?000). Conclusions The ERCC1 gene promoter methylation status may be involved in the development and progression of CSCC. It may also influence the sensitivity of patients with CSCC to cisplatin?based concurrent chemoradiotherapy by playing a role in cell differentiation.
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