Clinical Study · 临床研究

JAM3 Gene DNA Methylation in Predicting Cervical High-Grade Lesions & Postoperative Recurrence

JAM3 基因 DNA 甲基化在宫颈高级别上皮内瘤变及术后复发预测的临床研究
200 biopsy cases (normal/CIN I/II/III × 50) · methylation gradient 4%→54% · recurrence prediction
娄琰琰、刘元涛、赵淑婷、陈青、曹佃霞、公维涛、郝长宏 · 临沂市中心医院妇科/疼痛科/病理科
Advances in Clinical Medicine 2024;14(7):1293-1299 · DOI 10.12677/acm.2024.1472146
200
biopsy cases
4%→54%
JAM3+ gradient
AUC
recurrence prediction
50×4
balanced groups

1Background & Objective

HSIL
key precursor
HPV
low specificity
TCT
subjective
  • Precursor burden: high-grade CIN untreated → substantial progression risk to invasive cancer.
  • Conventional limits: HPV low specificity; TCT low sensitivity & operator-dependent — imperfect grading.
  • Methylation rationale: JAM3 (tight-junction molecule) promoter methylation is a key epigenetic event in carcinogenesis.
  • Aim: JAM3 methylation for HSIL detection, CIN grading and postoperative recurrence prediction.

2Study Design

50×4
normal/CIN I/II/III
2020–2023
enrollment
Linyi
central hospital
  • Cases: 200 cervical biopsy cases requiring biopsy; single fixed sampler; histology-confirmed groups of 50 each.
  • Workup: HPV testing + liquid-based cytology (TCT) + JAM3 DNA methylation assay on pathological specimens.
  • Method: bisulfite-based methylation detection; agarose gel (2.0%, 1×TAE) + UV imaging; BiQAnalyzer analysis.
  • Statistics: ANOVA across groups; ROC & AUC for recurrence; cutoff (Ct) by ROC; P<0.01 significant.
HPV
genotyping
TCT
cytology
JAM3
methylation
  • Follow-up: recurrence tracked after treatment; recurrent vs cured comparison for prediction modeling.
  • Specimen: pathological-section DNA used for methylation; bisulfite conversion before PCR.
  • Endpoint: JAM3 methylation compared across grades and between recurrence vs cured patients.
LOU Y et al. · Adv Clin Med 2024 · 200 cases, four groups × 50 · pathological specimens.
设计要点：四组各 50 例、病理金标准确认；每位患者行 HPV、TCT 与 JAM3 甲基化三种检测，治疗后追踪复发。
核心结果：JAM3 甲基化阳性率随 CIN 分级显著升高（正常 4%→CIN III 54%，两两比较 P<0.01），并支持术后复发预测。
联合价值：JAM3 甲基化与 HPV、TCT 互补，提升高级别 CIN 检出，为个体化术后随访提供客观依据。
随访意义：ROC 确定 Ct 阈值后，JAM3 甲基化可辅助判断复发风险，指导随访频率与干预时机。

3JAM3 Methylation Rises with Lesion Grade

Normal
4%
4%
CIN I
10%
10%
CIN II
38%
38%
CIN III
54%
54%
  • Progressive gradient: JAM3+ rises 4% → 10% → 38% → 54% across severity.
  • All pairwise significant: normal vs CIN I vs CIN II vs CIN III differences P<0.01.
  • Grading support: methylation mirrors histologic grade — aids CIN II/III discrimination.

4Postoperative Recurrence Prediction

ROC
cutoff by Ct
AUC
recurrence
P<0.01
significant
  • Recurrence vs cured: JAM3 methylation compared between recurrent and cured patients after treatment.
  • ROC-based cutoff: Ct threshold derived to discriminate recurrence with high accuracy.
  • Clinical track: methylation adds an objective signal for post-treatment surveillance.

5Complement to HPV & TCT

  • HPV shortfall: high sensitivity but low specificity — JAM3 methylation compensates false-positive burden.
  • TCT shortfall: low sensitivity & subjective — methylation adds objective molecular signal for high-grade lesions.
  • Combined use: joint detection raises detection rate of high-grade CIN beyond single conventional tests.
  • Surveillance role: postoperative recurrence prediction supports personalized follow-up intensity.
54%
JAM3+ in CIN III
38%
JAM3+ in CIN II
4%
normal
  • Objective marker: molecular readout independent of cytologist interpretation.
  • Cost-effective: same biopsy specimen — no additional invasive sampling.
Pathological-specimen DNA analyzed; results support JAM3 as an adjunct methylation marker in CIN management.
Clinical Significance