Abstract：
Cervical cancer (CaCx) is the malignancy of uterine cervix which induce by human papillomavirus (HPV) infections. HPV infection starts with the induction of double-stranded breaks by increasing oxidative stress and modulation of DNA repair pathways. Deficiency in DNA repair pathways and accumulation of DNA damage increases mutation rates resulting in genomic instability and cancer development. Patients with HPV-associated CaCx display increased sensitivity to cisplatin-based chemoradiotherapy (CRT) and improved survival rates. However, the cellular mechanisms responsible for this characteristic difference are unclear. Here, we have evaluated expression of DNA repair genes in peripheral blood cells and correlated them with treatment outcomes. A total of 211 study subjects includes in the study comprised 103 CaCx patients and 108 healthy controls. All the study subjects were analyzed for the expression profile of DNA repair genes by using real-time PCR (RT-PCR). The differentially expressed DNA repair gene was correlated with the treatment outcome of CRT. OGG1, XRCC2, XRCC3, XRCC4 and XRCC6 genes were found to be significant (P = 0.001) down-regulated as compared to controls. While XRCC5 and RAD51 showed significant up-regulated (P = 0.024 and 0.041) in CaCx patients. XRCC6 was associated (P = 0.033) with poor vital while up-regulated RAD51 showed slight association (P = 0.075) with better vital with an increased 2.96- and 2.33-fold risk in the study population. In the case of overall survival, down-regulated XRCC4 was associated (P = 0.042) with poor survival (27 months) with the least hazard ratio (0.56 HR). Down-regulated OGG1 involved BER, XRCC2 and XRCC3 in homologous recombination and XRCC4, XRCC5 and XRCC6 in Non-homologous end-joining repair, which showed a deficiency of DNA repair capacity resulting caused of an accumulation of DNA damage and genome instability. Impaired DNA repair gene expression is responsible for poor prognosis and survival in CaCx. Therefore, these gene expressions can be considered a potential prognostic, diagnostic and therapeutic biomarker for CaCx.
摘要：
宫颈癌（CaCx）是由人乳头瘤病毒（HPV）感染引起的子宫颈恶性肿瘤。HPV感染开始于通过增加氧化应激和DNA修复途径的调节来诱导双链断裂。DNA修复途径的缺陷和DNA损伤的积累增加了突变率,导致基因组不稳定和癌症发展。HPV相关CaCx患者对基于顺铂的放化疗（CRT）的敏感性增加，生存率提高。然而,造成这种特征差异的细胞机制尚不清楚.这里,我们评估了外周血细胞中DNA修复基因的表达,并将其与治疗结果相关联.总共211个研究对象包括103个CaCx患者和108个健康对照。通过使用实时PCR(RT-PCR)分析所有研究对象的DNA修复基因的表达谱。差异表达的DNA修复基因与CRT的治疗结果相关。与对照相比,发现OGG1、XRCC2、XRCC3、XRCC4和XRCC6基因显著下调(P=0.001)。而XRCC5和RAD51在CaCx患者中显示显著上调(P=0.024和0.041)。XRCC6与不良生命相关（P=0.033），而上调的RAD51与更好的生命相关（P=0.075），在研究人群中风险增加了2.96倍和2.33倍。在总体生存率的情况下，XRCC4下调(P=0.042)与不良生存(27个月)相关,风险比最小(0.56HR).下调的OGG1涉及BER，XRCC2和XRCC3在同源重组中，XRCC4，XRCC5和XRCC6在非同源末端连接修复中，这表明DNA修复能力不足，导致DNA损伤和基因组不稳定的积累。受损的DNA修复基因表达是导致CaCx预后不良和存活的原因。因此,这些基因表达可以被认为是潜在的预后因素，CaCx的诊断和治疗生物标志物。
