Association of elevated E6 oncoprotein with grade of cervical neoplasia using PDZ interaction-mediated precipitation of E6.

Association of elevated E6 oncoprotein with grade of cervical neoplasia using PDZ interaction-mediated precipitation of E6.
复制标题

使用 PDZ 相互作用介导的 E6 沉淀研究升高的 E6 癌蛋白与宫颈肿瘤分级的关联。

DOI:
10.1097/lgt.0b013e3181f6c84d
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发表时间:
2011
影响因子:
3.7
通讯作者:
Labiad,YassineA
Labiad,YassineA
中科院分区:
医学4区
文献类型:
--
作者:
Sellors,JohnW;Schweizer,JohannesG;Lu,PeterS;Liu,Bin;Weigl,BernhardH;Cui,JianFeng;Peck,RogerB;Lewis,Kristen;Lim,Jeanette;Howard,Michelle;Mahoney,CharlesW;McAllister,Linda;Berard-Bergery,Marthe;Bry,Claire;Labiad,YassineA

文献摘要

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目标。目的测定宫颈上皮内瘤变(CIN)妇女宫颈标本中人乳头瘤病毒(HPV) 16型E6癌蛋白的表达。材料与方法。来自中国山西的2530名年龄在30至54岁之间的未筛查妇女的宫颈标本。所有女性均通过液体细胞学检查、高危HPV DNA检测、阴道镜检查(必要时进行定向活检和宫颈内膜刮除)进行评估。细胞学结果异常或HPV DNA结果阳性的妇女被召回进行阴道镜检查、四象限宫颈活检和宫颈内膜刮除。通过HPV-16 E6 dna特异性聚合酶链反应检测经活检证实的CIN和癌症妇女以及hc2阳性、疾病阴性妇女的方便样本是否存在HPV-16感染。采用PDZ相互作用介导的E6癌蛋白沉淀法对HPV-16感染女性标本进行E6特异性Western blot检测。E6癌蛋白表达升高与CIN 2和CIN 3之间的关系通过logistic回归和CIN 1和疾病阴性的参考分类来确定。在证实HPV-16感染的妇女标本中检测HPV-16 E6癌蛋白的显著趋势是:阴性结果为CIN 1、2和3的妇女中分别为0%(0/12)、12.5%(1/8)、36.4%(4/11)和42.9%(3/7)(p=。01)。与阴性结果与CIN 1相结合的分类相比,E6癌蛋白检测与CIN 2相关(优势比= 10.9,p=。0.05)和CIN 3(优势比= 14.3,p= 0.05)。.Conclusions 04)。E6癌蛋白表达升高与CIN的分级有显著相关性。这一发现似乎与E6癌蛋白在癌变过程中所起的作用一致。
Objective.To determine the expression of human papillomavirus (HPV) type 16 E6 oncoprotein in cervical specimens of women with and without cervical intraepithelial neoplasia (CIN).Materials and Methods.Cervical specimens from 2,530 unscreened women aged 30 to 54 years from Shanxi, China, were obtained. All women were assessed by liquid-based cytology, high-risk HPV DNA tests, and colposcopy with directed biopsy and endocervical curettage as necessary. Women with abnormal cytologic results or positive HPV DNA results were recalled for colposcopy, 4-quadrant cervical biopsies, and endocervical curettage. Women with biopsy-proven CIN and cancer and a convenience sample of HC2-positive, disease-negative women were tested for the presence of HPV-16 infection via HPV-16 E6 DNA-specific polymerase chain reaction. A PDZ interaction-mediated E6 oncoprotein precipitation method followed by E6-specific Western blot was performed on specimens from women with HPV-16 infections. Associations between elevated expression of E6 oncoprotein and CIN 2 and 3 were determined using logistic regression and a reference category of CIN 1 and disease-negative.Results.A significant trend for the detection of HPV-16 E6 oncoprotein in specimen of women with proven HPV-16 infection was determined: 0%(0/12), 12.5%(1/8), 36.4%(4/11), and 42.9%(3/7) of those with negative findings, CIN 1, 2, and 3, respectively (p=. 01). Compared with the category combining negative findings and CIN 1, detection of E6 oncoprotein was associated with CIN 2 (odds ratio= 10.9, p=. 05) and CIN 3 (odds ratio= 14.3, p=. 04).Conclusions.There is a significant association between elevated expression of E6 oncoprotein and grade of CIN. This finding seems consistent with the role played by E6 oncoprotein in carcinogenesis.