宫颈癌组织LIG4、XRCC4、XRCC5、XRCC6、XRCC7的mRNA表达及与放疗敏感性的关系

The Relationship between Radiosensitivity and DNA Double Strand Breaks Repair Genes in Non-homologous End Joining Pathway in Human Cervical Carcinoma

目的研究DNA双链断裂非同源末端链接(NHEJ)修复通路中DNA连接酶IV(LIG4)、X射线修复交叉互补基因4、5、6、7(XRCC4、XRCC5、XRCC6、XRCC7)的mRNA表达水平与宫颈癌组织放射敏感性的关系。方法应用实时荧光定量RT-PCR技术检测61例宫颈癌组织中的LIG4、XRCC4、XRCC5、XRCC6和XRCC7的mRNA表达量,依据WHO实体瘤疗效评定标准,将放疗后的宫颈癌患者分为放疗高敏感组和放疗低敏感组,对比两组间以上基因表达水平的差异。结果 61例宫颈癌患者放疗后疗效评价为完全缓解(CR):60.7%(37/61),部分缓解及无变化(PR+NC):39.3%(24/61)。据此分为宫颈癌放疗高敏感组(CR)与放疗低敏感组(PR+NC)。放疗高敏感组LIG4mRNA、XRCC4mRNA、XRCC5mRNA、XRCC6mRNA、XRCC7mRNA在宫颈癌组织中的表达分别为0.84±0.60、1.46±0.58、2.07±1.09、0.54±0.23和0.60±0.34;放疗低敏感组为1.30±0.50、2.08±0.75、2.96±1.07、0.72±0.17和0.90±0.27,两组比较差异均有统计学意义(t=2.54、3.24、2.70、2.73、2.97,P=0.014、0.002、0.009、0.008、0.004)。结论患者宫颈癌组织中LIG4、XRCC4、XRCC5、XRCC6和XRCC7的mRNA高表达者,其对放疗抗拒,低表达则放疗高度敏感,上述基因可能成为预测宫颈癌放疗敏感性的指标和放疗增敏的分子靶点。

Objective To investigate the correlation between expression levels of the five key genes in Non - homologous End Joining Pathway （NHEJ） and radiosensitivity in cervical carcinoma tissues. Methods The mRNA expression levels of LIG4 ,XRCC4, XRCCS, XRCC6, XRCC7 were detected by real-time quantitative reverse transcription-polymerase chain reaction （QRT- PCR） method in 61 cervical carcinoma tissues. Ac-cording to the World Health Orgnization solid tumor response judgment standard, the patients with cervical carcinoma were divided into two groups, which were high radiosensitive and low radiosensitive. The mRNA ex-pressions of LIG4,XRCC4,XRCC5 ,XRCC6,XRCC7 were compared in the two groups. Results In 61 cases with cervical carcinoma after radiotherapy, complete response（CR） were 60.7% （37/61） , partial response and no Change （PR ＋ NC） were 39.3% （24/61）. The mRNA expression levels of LIG4,XRCC4,XRCCS, XRCC6,and XRCC7 between the high radiosensitive group（CR） and the low radiosensitive group（PR ＋ NC） were respectively 0.84 ± 0.60,1.46 ± 0.58,2.07 ± 1.09,0.54 ± 0.23,0.60 ± 0.34 and 1.30±0.50, 2.08 ±0.75,2.96 ± 1.07,0.72 ± 0.17 和 0.90 ± 0.27. There were statistical significance between the two groups in the five genes expressions respectively （P ≤0.05 ）. Conclusion The high gene expression levels of LIG4,XRCC4,XRCC5,XRCC6 and XRCC7 in cervical carcinoma tissues displayed radioresistance, on the contrary, the low expression levels of them displayed radiosensitivity. They might forecast radiosensitivity of cervical cancer and might be molecular targets of radiotherapy sensitization.