JAM3 methylation status as a biomarker for diagnosis of preneoplastic and neoplastic lesions of the cervix
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Aijun Yin1, Qing Zhang1, Xiangnan Kong2, Lin Jia1, Ziyan Yang1, Lihua Meng1, Li Li3, Xiao Wang3, Yunbo Qiao1, Nan Lu4, Qifeng Yang5,6, Keng Shen7, Beihua Kong1
1Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan, P.R. China
2Laboratory Medicine Center, Qilu Hospital of Shandong University, Qingdao, P.R. China
3Institute of Pathology and Pathophysiology, Shandong University School of Medicine, Jinan, P.R. China
4Institute of Diagnostics, Shandong University School of Medicine, Jinan, P.R. China
5Department of Breast Surgery, Qilu Hospital, Shandong University, Jinan, P.R. China
6Pathology Tissue Bank, Qilu Hospital, Shandong University, Jinan, P.R. China
7Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P.R. China
Beihua Kong, e-mail: [email protected]
Keywords: JAM3, cervical neoplasia, methylation, triage, complementary
Received: August 16, 2015 Accepted: October 14, 2015 Published: October 27, 2015
DNA methylation is clinically relevant to important tumorigenic mechanisms. This study evaluated the methylation status of candidate genes in cervical neoplasia and determined their diagnostic performance in clinical practice. Cervical cancer and normal cervix tissue was used to select the top 5 discriminating loci among 27 loci in 4 genes (CCNA1, CADM1, DAPK1, JAM3), and one locus of JAM3 (region M4) was identified and confirmed with 267 and 224 cervical scrapings from 2 independent colposcopy referral studies. For patients with atypical squamous cells of unknown significance and those with low-grade squamous intraepithelial lesion, with JAM3-M4 compared to a triage marker of hrHPV testing, the specificity for cervical intraepithelial neoplasia 3 CIN3 and cancer cases (CIN3+) / no neoplasia and CIN1 (CIN1−) was significantly increased, from 21.88 to 81.82 and 15.38 to 85.18, respectively. The corresponding positive predictive value (PPV) was increased from 26.47 to 57.14 and 18.52 to 63.64, respectively. For hrHPV-positive patients, compared to a triage marker of cytology testing, JAM3-M4 showed increased specificity and PPV, from 30.67 to 87.65 and 38.82 to 82.14, respectively. We assessed whether JAM3-M4 could distinguish productive from transforming CIN2; the coincidence rate of JAM3-M4 and P16 was as high as 60.5%.
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