宫颈癌前病变PAX1基因DNA甲基化检测与HPV-DNA分型检测的效果比较

摘要
图/表
参考文献
相关文章 (12)

全文: PDF (1005 KB)
输出: BibTeX | EndNote (RIS)

摘要目的分析PAX1基因甲基化与HPV-DNA分型检测在宫颈癌前病变诊疗中的特征及潜在关联。方法选择2021-06至2022-03在解放军总医院第三医学中心妇产科行液基薄层细胞检测(TCT)和人乳头瘤病毒-DNA(HPV-DNA)分型检测的患者。纳入研究TCT结果异常,意义不明的非典型鳞状细胞(ASCUS)和(或)HR-HPV阳性患者194例,宫颈组织病变筛查结果异常并转诊阴道镜下取病理活检的患者共130例。所有患者进行TCT、HPV-DNA分型检测、定量PAX1基因甲基化检测。结果 CIN3+(CIN3和宫颈癌)患者的PAX1基因甲基化数值显著高于正常、CIN1、CIN2患者,按照活检病理级别从高到低PAX1基因甲基化数值依次分别为18.21(17.56,18.66)和20.5(20.07,20.80),20.41(20.19,20.72),20.21(19.77,20.42);TCT结果提示ASCUS的患者共45例,CIN2+(CIN2、CIN3和宫颈癌)PAX1基因甲基化数值显著高于正常/CIN1,按照活检病理级别从高到低PAX1基因甲基化数值依次分别为 18.87(17.80,20.26)和 20.51(20.19,20.73);HPV16、18阳性患者的PAX1基因甲基化数值均显著高于非HPV16/18阳性患者,HPV16阳性和高危型非HPV16/18阳性患者PAX1基因甲基化数值分别为19.10(17.97,19.88)和20.33(20.00,20.50),HPV18阳性和非HPV16/18阳性患者PAX1基因甲基化水平分别为19.49(18.65,20.31)和20.33(20.00,20.50)。但单一HPV16阳性与单一HPV18阳性患者的PAX1基因甲基化数值相比,二者间的数值则无统计学差异。结论 PAX1基因甲基化检测有助于早期识别CIN3+和ASCUS宫颈高级别病变,也有助于降低ASCUS患者的阴道镜转诊率。

	服务

	把本文推荐给朋友
	加入我的书架
	加入引用管理器
	E-mail Alert
	RSS
	作者相关文章
	李佳璐
	董媛
	王宇
	张晓莉

关键词 ： PAX1基因甲基化检测, 人类乳头状病毒, DNA分型, 宫颈病变

Abstract：Objective To analyze the characteristics and potential correlation between PAX1 gene methylation and HPV-DNA typing in the diagnosis and treatment of cervical precancerous lesions. Methods Patients who underwent liquid-based thin-layer cell testing (TCT) and human papillomavirus DNA (HPV-DNA) typing in the Department of Obstetrics and Gynecology of the Third Medical Center of PLA General Hospital from June 2021 to March 2022 were selected. A total of 194 patients with abnormal TCT results≥ atypical squamous cells of unknown significance (ASCUS) and/or HR-HPV positive and 130 patients with abnormal cervical tissue screening results who were referred for colposcopic biopsy were included in this study. TCT, HPV-DNA typing and quantitative PAX1 gene methylation were performed in all patients. Results Compared with CIN3+ (CIN3 and cervical cancer) and normal/cervicitis, CIN1 and CIN2, the methylation value of PAX1 gene in CIN3+ patients was significantly higher than that in normal, CIN1 and CIN2 patients. The methylation values of PAX1 gene from high to low were 18.21 (17.56, 18.66), 20.5 (20.07, 20.80), 20.41 (20.19, 20.72), 20.21 (19.77, 20,42), respectively. The TCT results showed that there were 45 patients with ASCUS, CIN2+ (CIN2, CIN3 and cervical cancer) compared with normal/CIN1, and the methylation value of PAX1 gene CIN2+ was significantly higher than that of normal/CIN1. The methylation values of PAX1 gene from high to low were 18.87 (17.80, 20.26) and 20.51 (20.19, 20.73), respectively. The methylation values of PAX1 gene in HPV16 and 18 positive patients were significantly higher than those in non-HPV16/18 positive patients. The methylation values of PAX1 gene in HPV16 positive and high-risk non-HPV16/18 positive patients were 19.10 (17.97, 19.88) and 20.33 (20.00, 20.50), respectively. The methylation levels of PAX1 gene in HPV18-positive and non-HPV16/18 positive patients were 19.49 (18.65, 20.31) and 20.33 (20.00, 20.50), respectively. However, there was no significant difference in the methylation value of PAX1 gene between single HPV16 positive patients and single HPV18 positive patients). Conclusions The methylation of PAX1 gene is related with the progression of cervical lesions and the type of HPV infection. The methylation values of PAX1 gene in patients with single HPV16 positive and single HPV18 positive are significantly higher than those in patients without HPV16/18 positive. In ASCUS patients, the methylation value of PAX1 gene in CIN2+ is significantly higher than that in normal /CIN1. It is suggested that PAX1 gene methylation detection is helpful for early identification of CIN3+ and ASCUS cervical high-grade lesions, and also helps to reduce the colposcopy referral rate of ASCUS patients.

Key words： PAX1 methylation detection human papillomavirus DNA cervical lesions

收稿日期: 2022-07-11

ZTFLH:

R711.74

基金资助:首都科研发展专项项目(2020-1-5112)

通讯作者: 张晓莉,E-mail:wjzhangxiaoli@sina.cn

作者简介: 李佳璐,硕士研究生,医师。

引用本文:

李佳璐, 董媛, 王宇, 张晓莉. 宫颈癌前病变PAX1基因DNA甲基化检测与HPV-DNA分型检测的效果比较[J]. 武警医学, 2023, 34(1): 18-21. LI Jialu, DONG Yuan, WANG Yu, ZHNAG Xiaoli. Comparison of PAX1 gene DNA methylation detection and HPV-DNA typing in diagnosis and treatment of cervical precancerous lesions. Med. J. Chin. Peop. Armed Poli. Forc., 2023, 34(1): 18-21.

链接本文:

http://journal08.magtechjournal.com/Jwk_wjyx/CN/ 或 http://journal08.magtechjournal.com/Jwk_wjyx/CN/Y2023/V34/I1/18

[1]	王文文,邱丽华.DNA甲基化在卵巢癌中的研究进展[J].国际生殖健康/计划生育杂志, 2012, 31(4):312-315.
[2]	Kristensen L S, Hansen L L. PCR-based methods for detecting single-locus DNA methylation biomarkers in cancer diagnostics, prognostics, and response to treatment[J]. Clin Chem, 2009,55(8):1471-1483.
[3]	Doorbar J, Quint W, Banks L, et al. The biology and life-cycle of human papillomaviruses[J]. Vaccine, 2012, 30(5):F55-70.
[4]	Xu G, Liu Y, Zhang C, et al. Temporal and spatial expression of Sox9, Pax1, TGF-β1 and type I and II collagen in human intervertebral disc development[J]. Neurochirurgie, 2020, 66(3):168-173.
[5]	Aliani A, Abid H, Mallali Y, et al. Association between gene promoter methylation and cervical cancer development: global distribution and a meta-analysis[J]. Cancer Epidemiol Biomarkers Prev, 2021,30(3):450-459.
[6]	Lai H C, Ou Y C, Chen T C, et al. PAX1/SOX1 DNA methylation and cervical neoplasia detection: a taiwanese gynecologic oncology group(TGOG) study[J]. Cancer Med, 2014, 3(4): 1062-1074.
[7]	Kong L Y, Du W, Wang L, et al. PAX1 methylation hallmarks promising accuracy for cervical cancer screening in asians: results from a meta-analysis[J]. Clin Lab, 2015, 61(10):1471-1479.
[8]	Su P H, Lai H C, Huang R L, et al. Paired Box-1(PAX1) activates multiple phosphatases and inhibits kinase cascades in cervical cancer[J]. Sci Rep, 2019, 24, 9(1):9195.
[9]	陈飞, 尤志学,隋龙,等.阴道镜应用的中国专家共识[J].中华妇产科杂志, 2020,55(7): 443-449.
[10]	Cox J T, Schiffman M, Solomon D. Prospective follow-up suggests similar risk of subsequent cervical intraepithelial neoplasia grade 2 or 3 among women with cervical intraepithelial neoplasia grade 1 or negative colposcopy and directed biopsy[J]. Am J Obstet Gynecol, 2003, 188(6):1406-1412.
[11]	Basu P, Ponti A, Anttila A, et al. Status of implementation and organization of cancer screening in The European Union Member States-Summary results from the second European screening report[J]. Int J Cancer, 2018, 142(1):44-56.
[12]	Jaisamrarn U, Castellsagué X, Garland S M, et al. Natural history of progression of HPV infection to cervical lesion or clearance: analysis of the control arm of the large, randomised PATRICIA study[J]. PLoS One, 2013, 8(11):e79260.
[13]	Wentzensen N, Schiffman M, Palmer T, et al.Triage of HPV positive women in cervical cancer screening[J]. J Clin Virol, 2016, 76(Suppl 1):S49-55.
[14]	Kelly H, Benavente Y, Pavon M A, et al. Performance of DNA methylation assays for detection of high-grade cervical intraepithelial neoplasia(CIN2+): a systematic review and meta-analysis[J]. Br J Cancer, 2019, 121(11):954-965.
[15]	Fang C, Wang S Y, Liou Y L, et al. The promising role of PAX1(aliases: HUP48, OFC2) gene methylation in cancer screening[J]. Mol Genet Genomic Med, 2019, 7(3):e506.
[16]	Liu H, Meng X, Wang J. Real time quantitative methylation detection of PAX1 gene in cervical cancer screening[J]. Int J Gynecol Cancer, 2020, 30(10):1488-1492.
[17]	Curry S J, Krist A H, Owens D K, et al. Screening for cervical cancer: US preventive services task force recommendation statement[J]. JAMA, 2018, 320(7):674-686.
[18]	王文杰,余敏红,范世珍,等.人乳头瘤病毒(HPV)型别与SOX1和PAX1基因甲基化的相关性研究[J].中国实验诊断学,2020,24(8),1353-1356.
[19]	Güzel C, Sten H J, Kok I M, et al. Molecular markers for cervical cancer screening[J]. Expert Rev Proteomics, 2021,18(8):675-691.
[20]	Schmitz M, Wunsch K, Hoyer H, et al. Performance of a methylation specific real-time PCR assay as a triage test for HPV-positive women[J]. Clin Epigenet, 2017, 9:118.