Reduction in the copy number and expression level of the recurrent human papillomavirus integration gene fragile histidine triad (FHIT) predicts the transition of cervical lesions.
Reduction in the copy number and expression level of the recurrent human papillomavirus integration gene fragile histidine triad (FHIT) predicts the transition of cervical lesions.
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复发性人乳头瘤病毒整合基因脆性组氨酸三联体（FHIT）拷贝数和表达水平的降低预示着宫颈病变的转变
DOI：
10.1371/journal.pone.0175520
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Wang H
中科院分区：
文献类型：
--
作者：
Wang L;Shen H;Feng B;Zhu D;Yu L;Tian X;Ren C;Gao C;Li X;Ma D;Hu Z;Wang H
宫颈癌是全球女性中第二常见的癌症，也是癌症死亡的第三大原因，在发展中国家尤为如此。高危型人乳头瘤病毒（HR - HPV）感染导致宫颈癌以及宫颈癌前宫颈上皮内瘤变（CIN）。HR - HPV基因组整合到宿主染色质是宫颈癌发生的一个重要步骤。整合型乳头瘤病毒序列 - 聚合酶链反应（DIPS - PCR）检测使我们能够探究人乳头瘤病毒在人类基因组中的整合情况，并确定这种整合的模式。我们对4种细胞系（包括3种宫颈癌细胞系）以及40个组织样本进行了DIPS - PCR。总体而言，在临床样本以及HeLa和SiHa细胞系中检测到32个HR - HPV整合位点。在所有整合位点中，我们确定了三个反复出现的整合位点：3p14.2（3个样本）、13q22.1（2个样本和SiHa细胞系）以及8q24（1个样本和HeLa细胞系）。为了进一步探究HR - HPV在3p14.2位点整合的影响，我们使用荧光原位杂交（FISH）来确定3p14.2位点的拷贝数，并使用免疫组织化学（IHC）来确定临床样本中相关FHIT基因的蛋白质表达水平。当CIN发展为宫颈癌时，3p14.2位点拷贝数和FHIT蛋白表达水平均显著下降。我们还对这些临床样本中的HPV拷贝数进行了评估，HPV拷贝数在CIN和宫颈癌样本之间显著增加。最后，我们采用受试者工作特征曲线（ROC曲线）分析来评估所有这些指标在区分CIN和宫颈癌方面的潜力，HPV拷贝数、FHIT拷贝数以及FHIT蛋白表达水平都具有良好的诊断效能。
Cervical cancer is the second most common cancer and the third leading cause of cancer death in females worldwide, especially in developing countries. High risk human papillomavirus (HR-HPV) infection causes cervical cancer and precancerous cervical intraepithelial neoplasia (CIN). Integration of the HR-HPV genome into the host chromatin is an important step in cervical carcinogenesis. The detection of integrated papillomavirus sequences-PCR (DIPS-PCR) allowed us to explore HPV integration in the human genome and to determine the pattern of this integration. We performed DIPS-PCR for 4 cell lines including 3 cervical cancer cell lines and 40 tissue samples. Overall, 32 HR-HPV integration loci were detected in the clinical samples and the HeLa and SiHa cell lines. Among all the integration loci, we identified three recurrent integration loci: 3p14.2 (3 samples), 13q22.1 (2 samples and a SiHa cell line) and 8q24 (1 sample and a HeLa cell line). To further explore the effect of HR-HPV integration in the 3p14.2 locus, we used fluorescence in situ hybridization (FISH) to determine the copy number of the 3p14.2 locus and immunohistochemistry (IHC) to determine the protein expression levels of the related FHIT gene in the clinical samples. Both the 3p14.2 locus copy number and FHIT protein expression levels showed significant decreases when CIN transitioned to cervical cancer. HPV copy number was also evaluated in these clinical samples, and the copy number of HPV increased significantly between CIN and cervical cancer samples. Finally, we employed receiver operating characteristic curve (ROC curve) analysis to evaluate the potential of all these indexes in distinguishing CIN and cervical cancer, and the HPV copy number, FHIT copy number and FHIT protein expression levels have good diagnostic efficiencies.
影响因子：
8.8
作者：
Terry, G;Ho, L;Londesborough, P;Cross, P;Lopes, A;Monaghan, J;Cuzick, J
通讯作者：
Cuzick, J