DNA损伤修复相关基因Polζ、ERCC1、ERCC2和RAD52在宫颈癌中的表达及其临床意义

The Clinical Significance of Polζ,ERCC1,ERCC2 and RAD52 Expression in Cervical Cancer Tissues

[目的]评价DNA损伤修复相关基因在宫颈癌组织中的表达及其临床意义。[方法]纳入2008-2009年在复旦大学附属肿瘤医院行根治性手术并辅助同步放化疗的113例宫颈鳞状细胞癌患者,采用免疫组化法检测DNA损伤修复相关基因（Polζ,ERCC1,ERCC2和RAD52）在石蜡包埋组织中的蛋白表达水平。[结果 ]Polζ,ERCC1,ERCC2和RAD52的阳性表达率分别为22.1%,46.0%,48.7%和20.4%。Kaplan-Meier生存分析表明Polζ蛋白表达阳性的患者无进展生存期更短（32个月vs 34个月,P=0.008）。多因素生存分析显示Polζ是肿瘤复发的重要因素（adjusted HR=7.79,95%CI：2.21-27.52,P=0.001）。[结论]Polζ可作为宫颈癌判断预后的预测因素,这可能是由于宫颈癌患者潜在的放化疗抵抗导致的,该机制值得进一步研究。

[Purpose] To investigate the expression profiles of multiple DNA damage repair genes Polζ,ERCC1,ERCC2 and RAD52 in cervical cancer tissues and its clinical significance. [Methods] A total of 113 patients with squamous cell carcinoma of cervical cancer,who had adjuvant concurrent chemoradiation therapy after radical surgery treated at Fudan University Shanghai Can-cer Center between 2008 and 2009 were enrolled,and immunohistochemistry was used to test Polζ,ERCC1,ERCC2 and RAD52 protein expression in paraffin-embedded tissues. [Results] The positive expression of Polζ,ERCC1,ERCC2 and RAD52 was 22.1%,46.0%,48.7% and 20.4%,respectively. Kaplan-meier survival showed that the patients with Polζ-positive expression had a significantly shorter progression-free survival（32 months vs 34 months,P=0.008）. Multivariate Cox proportional hazards regression analysis revealed that Polζ protein expression（adjusted HR =7.79,95% CI：2.21 -27.52,P =0.001） was a significant predictor for recurrence/metastasis. [Conclusions] Polζ expression can serve as the predictor for poor prognosis in cervical cancer,which might due to the chemoradiation resistance of cervical cancer patients. The exact mechanism needs further research.