title: JAM3 methylation status as a biomarker for diagnosis of preneoplastic and neoplastic lesions of the cervix.
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%.
authors.affiliation: Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan, P.R. China.
authors.forename: Aijun
authors.initials: A
authors.lastname: Yin
authors.affiliation: Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan, P.R. China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Laboratory Medicine Center, Qilu Hospital of Shandong University, Qingdao, P.R. China.
authors.forename: Xiangnan
authors.initials: X
authors.lastname: Kong
authors.affiliation: Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan, P.R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Jia
authors.affiliation: Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan, P.R. China.
authors.forename: Ziyan
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan, P.R. China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Meng
authors.affiliation: Institute of Pathology and Pathophysiology, Shandong University School of Medicine, Jinan, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: Institute of Pathology and Pathophysiology, Shandong University School of Medicine, Jinan, P.R. China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan, P.R. China.
authors.forename: Yunbo
authors.initials: Y
authors.lastname: Qiao
authors.affiliation: Institute of Diagnostics, Shandong University School of Medicine, Jinan, P.R. China.
authors.forename: Nan
authors.initials: N
authors.lastname: Lu
authors.affiliation: Department of Breast Surgery, Qilu Hospital, Shandong University, Jinan, P.R. China.|Pathology Tissue Bank, Qilu Hospital, Shandong University, Jinan, P.R. China.
authors.forename: Qifeng
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P.R. China.
authors.forename: Keng
authors.initials: K
authors.lastname: Shen
authors.affiliation: Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan, P.R. China.
authors.forename: Beihua
authors.initials: B
authors.lastname: Kong
mesh_terms: D000328:Adult; D019540:Area Under Curve; D065309:Atypical Squamous Cells of the Cervix / Q000737:chemistry / Q000473:pathology / Q000821:virology; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D015815:Cell Adhesion Molecules / Q000235:genetics*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis; D019175:DNA Methylation; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D027383:Papillomaviridae / Q000302:isolation & purification; D030361:Papillomavirus Infections / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000821:virology; D016133:Polymerase Chain Reaction; D011230:Precancerous Conditions / Q000737:chemistry / Q000235:genetics* / Q000473:pathology / Q000821:virology; D011237:Predictive Value of Tests; D012372:ROC Curve; D015203:Reproducibility of Results; D065310:Squamous Intraepithelial Lesions of the Cervix / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000821:virology; D002583:Uterine Cervical Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology / Q000821:virology; D014626:Vaginal Smears; D002578:Uterine Cervical Dysplasia / Q000737:chemistry / Q000235:genetics* / Q000473:pathology / Q000821:virology
chemical_list: D014408:Biomarkers, Tumor; D015815:Cell Adhesion Molecules; D019941:Cyclin-Dependent Kinase Inhibitor p16; C448000:JAM3 protein, human
keywords: JAM3; cervical neoplasia; complementary; methylation; triage