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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。
Objective To investigate the relationship between the down-regulation of gene expression and the infection of human papillomavirus (HPV) in cervical cancer and precancerous lesions, and to provide basis for establishing the diagnostic index of cervical cancer for early warning of HPV screening. Methods A total of 100 specimens of fresh cervical epithelial tissue from Uighur women with cervical squamous cell carcinoma (CSCC), cervical intraepithelial neoplasia (CIN) Ⅱ ~ Ⅲ and cervicitis were collected and tissue DNA was extracted (RNAi) were selected to detect HPV positive and type. The RNA of HPV positive CSCC and CIN Ⅱ ~ Ⅲ and HPV negative cervicitis were selected and the expression of early growth response gene-1 (EGR1), DNA binding inhibitor 4 ID4), FBJ murine osteosarcoma proto-oncogene (FOS) and early emergency protein 2 (IER2) gene transcriptional expression levels. Results HPV positive identification and typing identified HPV16,18,45,31 and other eight types of HPV infection, cervical cancer, CIN and cervicitis tissue HPV positive rates were 94.4%, 75.0% and 31.3%, respectively, of which The positive rates of HPV16 were 66.6%, 68.7% and 31.3% respectively. The mRNA expression of EGR1, ID4, FOS and IER2 in HPV-positive CSCC tissues was lower than that of HPV-positive CIN and HPV-negative cervicitis. (P <0.05). However, the expression levels of four genes in HPV-positive CIN tissues were lower than those in HPV-negative cervicitis tissues (P <0.05), and there was significant difference in the expressions of EGR1 and ID4 <0.05). From the perspective of HPV16 infection, the expression of EGR1 and ID4 in CSCC or CIN was significantly different from that in cervicitis (P <0.05), but only the expression level of EGR1 in CSCC was significantly different from CIN (P <0.05), while there was no significant difference in ID4 gene (P> 0.05). Conclusion Cervical cancer and precancerous lesions are related to the down-regulation of EGR1 and ID4 gene expression depending on HPV infection. The change of EGR1 gene expression may be more closely related to the precancerous lesion and HPV16 infection, which may be the cervical cancer of early warning for HPV screening Auxiliary diagnostic indicators, and to reveal the pathogenesis of HPV infection and carcinogenesis provides an important basis for molecular mechanisms.