JAM3methylation status as a biomarker for diagnosis of preneoplastic and neoplastic lesions of the cervix

// Aijun Yin 1 , Qing Zhang 1 , Xiangnan Kong 2 , Lin Jia 1 , Ziyan Yang 1 , Lihua Meng 1 , Li Li 3 , Xiao Wang 3 , Yunbo Qiao 1 , Nan Lu 4 , Qifeng Yang 5, 6 , Keng Shen 7 , Beihua Kong 1 1 Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan, P.R. China 2 Laboratory Medicine Center, Qilu Hospital of Shandong University, Qingdao, P.R. China 3 Institute of Pathology and Pathophysiology, Shandong University School of Medicine, Jinan, P.R. China 4 Institute of Diagnostics, Shandong University School of Medicine, Jinan, P.R. China 5 Department of Breast Surgery, Qilu Hospital, Shandong University, Jinan, P.R. China 6 Pathology Tissue Bank, Qilu Hospital, Shandong University, Jinan, P.R. China 7 Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P.R. China Correspondence to: Beihua Kong, e-mail: kongbeihua@sdu.edu.cn Keywords: JAM3, cervical neoplasia, methylation, triage, complementary Received: August 16, 2015      Accepted: October 14, 2015      Published: October 27, 2015 ABSTRACT 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%.