PMID- 28414756 OWN - NLM STAT- MEDLINE DCOM- 20170425 LR - 20221207 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 12 IP - 4 DP - 2017 TI - 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. PG - e0175520 LID - 10.1371/journal.pone.0175520 [doi] LID - e0175520 AB - 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. FAU - Wang, Liming AU - Wang L AUID- ORCID: 0000-0003-3354-2079 AD - Key Laboratory of Cancer Invasion and Metastasis of the Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. FAU - Shen, Hui AU - Shen H AD - Key Laboratory of Cancer Invasion and Metastasis of the Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. FAU - Feng, Bei AU - Feng B AD - Key Laboratory of Cancer Invasion and Metastasis of the Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. FAU - Zhu, Da AU - Zhu D AD - Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. FAU - Yu, Lan AU - Yu L AD - Key Laboratory of Cancer Invasion and Metastasis of the Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. FAU - Tian, Xun AU - Tian X AD - Key Laboratory of Cancer Invasion and Metastasis of the Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. FAU - Ren, Ci AU - Ren C AD - Key Laboratory of Cancer Invasion and Metastasis of the Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. FAU - Gao, Chun AU - Gao C AD - Key Laboratory of Cancer Invasion and Metastasis of the Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. FAU - Li, Xiaomin AU - Li X AD - Key Laboratory of Cancer Invasion and Metastasis of the Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. FAU - Ma, Ding AU - Ma D AD - Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. FAU - Hu, Zheng AU - Hu Z AD - Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. AD - Department of Obstetrics and Gynecology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China. FAU - Wang, Hui AU - Wang H AUID- ORCID: 0000-0001-6789-5185 AD - Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. LA - eng PT - Journal Article DEP - 20170417 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (DNA, Viral) RN - 0 (Neoplasm Proteins) RN - 0 (fragile histidine triad protein) RN - EC 3.6.- (Acid Anhydride Hydrolases) SB - IM MH - Acid Anhydride Hydrolases/*genetics MH - Adult MH - Cell Line, Tumor MH - DNA, Viral/genetics MH - Female MH - Gene Dosage/*genetics MH - HeLa Cells MH - Humans MH - Immunohistochemistry/methods MH - In Situ Hybridization, Fluorescence/methods MH - Middle Aged MH - Neoplasm Proteins/*genetics MH - Papillomaviridae/*genetics MH - Papillomavirus Infections/*genetics/virology MH - Uterine Cervical Neoplasms/*genetics/virology MH - Uterine Cervical Dysplasia/genetics/virology PMC - PMC5393568 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2017/04/18 06:00 MHDA- 2017/04/26 06:00 PMCR- 2017/04/17 CRDT- 2017/04/18 06:00 PHST- 2016/12/30 00:00 [received] PHST- 2017/03/27 00:00 [accepted] PHST- 2017/04/18 06:00 [entrez] PHST- 2017/04/18 06:00 [pubmed] PHST- 2017/04/26 06:00 [medline] PHST- 2017/04/17 00:00 [pmc-release] AID - PONE-D-16-51529 [pii] AID - 10.1371/journal.pone.0175520 [doi] PST - epublish SO - PLoS One. 2017 Apr 17;12(4):e0175520. doi: 10.1371/journal.pone.0175520. eCollection 2017.