首页> 中文期刊> 《新疆医科大学学报》 >维吾尔族妇女宫颈癌及癌前病变组织中 EGR1和 ID4基因表达下调与 HPV 感染的关系

维吾尔族妇女宫颈癌及癌前病变组织中 EGR1和 ID4基因表达下调与 HPV 感染的关系

         

摘要

Objective To study the relationship between HPV infection and down-regulated genes of cervical cancer and precancerous lesions and to provide evidence for the establishment of auxiliary diagnostic markers of cervical cancer on the basis of the HPV screening.Methods 100 cases of fresh tissue specimens of Cervical squamous cell carcinoma (CSCC),cervical intraepithelial neoplasia (CIN),and cer-vicitis from Uyghur women patients were collected.Total RNA and DNA were extracted from fresh tissue,HPV positivity and genotypes were detected.Then we selected the HPV positive CSCC,CINⅡ-Ⅲ and HPV negative cervicitis tissue samples in the analysis of transcription levels of EGR1,ID4,FOS and IER2 by real-time RT-PCR.Results 8 HPV genotypes including HPV16,18,45,31 etc.have been detected in this study.The HPV positive ratio of Cervical,CINⅡ-Ⅲ and Cervicitis were 94.4%,75.0%and 31.3%,and the HPV16 ratio were 66.6%,68.7% and 31.3% respectively.The mRNA expression of EGR1,ID4,FOS and IER2 genes in HPV positive CSCC were significantly decreased (P < 0.05 ) compared with HPV positive CINⅡ-Ⅲ and HPV negative Cervicitis,and significant difference was found in EGR1 and ID4 expression between CINⅡ-Ⅲ and Cervicitis (P <0.05).In terms of HPV16 infection, EGR1 and ID4 gene expression level decreased significantly between CSCC or CINⅡ-Ⅲ and Cervicitis, but statistical difference between CSCC and CINⅡ-Ⅲ was only found for EGR1 (P <0.05).Conclusion The HPV-dependent down-regulation of EGR1 and ID4 gene expression at the transcriptional level is close-ly associated with the cervical cancer and precancerous lesion,and the change of EGR1 gene expression level is strongly related to precancerous lesion and HPV16 infection,which may serve as a HPV screening-based diagnostic marker of cervical cancer and provide the basis of revealing the pathogenic and carcinogenic molecular mechanisms of HPV infection in Uyghur women patients.%目的:探讨宫颈癌及癌前病变组织中基因下调表达调控与人乳头状瘤病毒(human papillomavirus, HPV)感染的依存关系,为建立 HPV 筛查预警的宫颈癌辅助诊断指标提供依据。方法收集维吾尔族妇女官颈鳞癌(cervical squamous cell carcinoma,CSCC)、宫颈上皮内瘤变(cervical intraepithelial neoplasia,CIN)Ⅱ~Ⅲ及宫颈炎患者的新鲜宫颈上皮组织标本共100例,提取组织 DNA 和 RNA,鉴定 HPV 阳性和型别,选择 HPV 阳性CSCC 和 CINⅡ~Ⅲ及 HPV 阴性宫颈炎组织 RNA,利用荧光定量 RT-PCR 方法鉴定早期生长反应基因-1(EGR1)、DNA 结合抑制因子4(ID4)、FBJ 鼠科骨肉瘤病毒原癌基因(FOS)和早期应急蛋白2(IER2)基因的转录表达水平。结果通过 HPV 阳性鉴定和分型,鉴别出 HPV16、18、45、31等8种 HPV 感染型别,宫颈癌、CIN 和宫颈炎组织的 HPV 阳性率分别为94.4%、75.0%和31.3%,其中 HPV16阳性率为66.6%、68.7%和31.3%;HPV 阳性的 CSCC 组织中 EGR1、ID4、FOS 和 IER2基因的 mRNA 表达水平低于 HPV 阳性的 CIN 和 HPV 阴性宫颈炎,且 CSCC 与 CIN 或 NC 比较差异均有统计学意义(P <0.05),而 HPV 阳性的 CIN 组织中4种基因的表达水平均低于 HPV 阴性的宫颈炎组织,两者 EGR1和 ID4基因表达水平差异有统计学意义(P <0.05);从 HPV16感染的角度分析,CSCC 或 CIN 与宫颈炎 EGR1和 ID4表达水平差异有统计学意义(P <0.05),但是 CSCC 与 CIN 相比较,只有 EGR1基因表达水平差异有统计学意义(P <0.05),而 ID4基因差异无统计学意义(P >0.05)。结论宫颈癌及癌前病变与依赖于 HPV 感染的 EGR1和 ID4基因表达下调有关,其中 EGR1基因表达水平变化可能与癌前病变和 HPV16感染的关系更为密切,可能成为 HPV 筛查预警的宫颈癌辅助诊断指标,并为揭示 HPV感染的致病和致癌分子机制提供了重要依据。

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