FAM19A4、PAX1及miRNA124-2基因启动子区甲基化在宫颈病变早期诊断中的价值

李雅; 刘慧; 任静静; 李肖甫; 智艳芳

doi:10.19401/j.cnki.1007-3639.2024.08.003

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FAM19A4、PAX1及miRNA124-2基因启动子区甲基化在宫颈病变早期诊断中的价值

论著 | 更新时间：2025-12-31

- FAM19A4、PAX1及miRNA124-2基因启动子区甲基化在宫颈病变早期诊断中的价值
- Early diagnostic value of methylation in promoter region of FAM19A4, PAX1 and miRNA124-2 in cervical lesions
- 中国癌症杂志 2024年34卷第8期页码：734-744
- 作者机构：
  
  郑州大学第三附属医院输血科，河南郑州 450052
- 作者简介：
  
  [ "李雅（ORID：0009-0007-0917-0291），硕士研究生，主管检验师。" ]
  智艳芳（ORID：0000-0003-1578-8358），主任技师/副教授，主任。
- 基金信息：
  
  河南省医学科技攻关计划省部共建重大项目(SBGJ202101020);河南省医学科技攻关计划（联合共建）项目(LHGJ20190392)
- DOI：10.19401/j.cnki.1007-3639.2024.08.003
  中图分类号： R737.33
- 收稿：2024-01-16，
  
  修回：2024-04-16，
  
  纸质出版：2024-08-30
- 稿件说明：
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李雅, 刘慧, 任静静, 等. FAM19A4、PAX1及miRNA124-2基因启动子区甲基化在宫颈病变早期诊断中的价值[J]. 中国癌症杂志, 2024,34(8):734-744.

Ya LI, Hui LIU, Jingjing REN, et al. Early diagnostic value of methylation in promoter region of FAM19A4, PAX1 and miRNA124-2 in cervical lesions[J]. China Oncology, 2024, 34(8): 734-744.
李雅, 刘慧, 任静静, 等. FAM19A4、PAX1及miRNA124-2基因启动子区甲基化在宫颈病变早期诊断中的价值[J]. 中国癌症杂志, 2024,34(8):734-744. DOI： 10.19401/j.cnki.1007-3639.2024.08.003.

Ya LI, Hui LIU, Jingjing REN, et al. Early diagnostic value of methylation in promoter region of FAM19A4, PAX1 and miRNA124-2 in cervical lesions[J]. China Oncology, 2024, 34(8): 734-744. DOI： 10.19401/j.cnki.1007-3639.2024.08.003.

摘要

背景与目的：

目前有关宫颈病变的DNA甲基化研究较多，但DNA甲基化作为宫颈病变的诊断及分流指标在临床实践中的报道较少。本研究拟探讨

FAM

4、

PAX

1及miRNA124-2基因启动子区甲基化在宫颈病变进展中早期诊断的价值。

方法：

收集2020年3月—2022年3月在郑州大学第三附属医院同时行宫颈液基细胞学（thinprep cytologic test，TCT）和HPV检测的患者的宫颈细胞学标本共129例，采用甲基化特异性PCR（methylation-speci

fic PCR，MSP）检测不同宫颈病变中

FAM

4、

PAX

1及miRNA124-2基因启动子区甲基化改变情况，采用受试者工作特征（receiver operating characteristic，ROC）曲线评估3个基因甲基化改变对宫颈病变的诊断价值。本研究经郑州大学第三附属医院伦理委员会批准（伦理审批编号：2023-135-01）。

结果：

根据病理学检查结果分为4组：未见上皮内病变或恶性细胞（no intraepithelial lesions or malignant lesions，NILM）组（42例）、低度鳞状上皮内病变（low grade squamous intraepithelial lesion，LSIL）组（28例）、高度鳞状上皮内病变（high grade squamous intraepithelial lesion，HSIL）组（36例）和鳞癌（squamous cervical cancer，SCC）组（23例）。随宫颈病变级别的增加，

FAM

4、

PAX

1及miRNA124-2基因甲基化检出率逐步增高，差异有统计学意义（

均

0.05）。在HSIL组

FAM

4、

PAX

1、miRNA124-2甲基化检出率分别为81.2%、80.5%和71.8%，在SCC组3种基因甲基化检出率均高达100.0%；细胞学诊断宫颈癌的ROC曲线下面积（area under curve，AUC）为0.731，诊断灵敏度和特异度分别为65.9%和80.4%；

FAM

4、

PAX

1及miRNA124-2基因单独诊断HSIL+（HSIL和SCC）时，

PAX

1甲基化诊断HSIL+的效能最高，AUC为0.925，灵敏度为92.8%，特异度为87.3%；两两联合诊断时，

FAM

4与

PAX

1联合诊断HSIL+的AUC为0.930，灵敏度为95.7%，特异度为87.1%；

FAM

4与miRNA124-2联合诊断HSIL+，AUC为0.895，灵敏度为97.6%，特异度为85.7%；

PAX

1联合miRNA124-2诊断HSIL+，AUC为0.928，灵敏度为95.7%，特异度为89.1%；

PAX

1、

FAM

4及miRNA124-2基因甲基化联合诊断HSIL+，AUC为0.928，灵敏度为100.0%，特异度为81.8%。

结论：

FAM

4、

PAX

1及miRNA124-2基因启动子区甲基化诊断宫颈病变具有较高的灵敏度和特异度，有潜力成为宫颈病变早期诊断的新指标。

Abstract

Background and purpose:

At present

there have been many reports on the study of methylation in cervical lesions

however it is still not clinically practical as a diagnostic and shunting index of cervical lesions. In this study

we intended to investigate the early diagnostic value of

FAM

PAX

1 and miRNA124-2 methylation in promoter region in the progression

of cervical lesions.

Methods:

A total of 129 liquid-based cytology specimens of different grades of cervical lesions diagnosed in the Third Affiliated Hospital of Zhengzhou University from Mar. 2020 to Mar. 2022. Methylation specific PCR (MSP) was used to detect the methylation changes of

FAM

PAX

1 and miRNA124-2 genes in different cervical lesions. Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of methylation changes of the three genes in cervical lesions. This study was approved by the Ethics Committee of the Third Affiliated Hospital of Zhengzhou University (No. 2023-135-01).

Results:

All the specimens were collected and divided into 4 groups according to the histological results: 42 cases of no intraepithelial lesions or malignant lesions (NILM)

28 cases of low grade squamous intraepithelial lesion (LSIL)

36 cases of high grade squamous intraepithelial lesion (HSIL)

23 cases of squamous cervical cancer (SCC). With the increase in the level of cervical lesions

FAM

PAX

1 and miRNA124-2 gene methylation detection rates increased gradually

and the differences were statistically significant (

0.05). The methylation detection rates of

FAM

PAX

1 and miRNA124-2 in HSIL group were 81.2%

80.5% and 71.8%

respectively

and the methylation detection rates of three genes in SCC group were up to 100.0%. Cytological diagnosis of cervical cancer showed the area under curve (AUC) was 0.731

with a sensitivity and a specificity of 65.9% and 80.4%

respectively. When

FAM

PAX

1 and miRNA124-2 were used alone to diagnose HSIL+ (HSIL and SCC)

PAX

1 methylation had the highest diagnostic efficiency

and the AUC was 0.925

with a sensitivity and a specificity of 92.8% and 87.3%. When the diagnosis was made i

n pairs

the AUC of

FAM

4 combined with

PAX

1 in the diagnosis of HSIL+ was 0.930

with a sensitivity and a specificity of 95.7% and 87.1%

respectively. The AUC of

FAM

4 combined with miRNA124-2 in the diagnosis of HSIL+ was 0.895

with a sensitivity and a specificity of 97.6% and 85.7%

respectively. The AUC of

PAX

1 combined with miRNA124-2 in the diagnosis of HSIL+ was 0.928

with a sensitivity and a specificity of 95.7% and 89.1%

respectively. When the

PAX

1 and

FAM

4 combined with miRNA124-2 in the diagnosis of HSIL+

the AUC was 0.928

with a sensitivity and a specificity of 100.0% and 81.8%

respectively.

Conclusion:

The methylation of the promoter regions of the

FAM

PAX

1 and miRNA124-2 genes demonstrates high sensitivity and specificity in diagnosing cervical lesions

indicating the potential for becoming novel indicators for early diagnosis of cervical lesions.

关键词

Keywords

references

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