您的位置：山东大学 -> 科技期刊社 -> 《山东大学学报（医学版）》

山东大学学报 (医学版) ›› 2021, Vol. 59 ›› Issue (11): 48-52.doi: 10.6040/j.issn.1671-7554.0.2021.0795

• 临床医学 • 上一篇    下一篇

PAX1基因甲基化与宫颈高级别上皮内病变及高危型HPV分型的关联性

梁婷婷,杨勇霞,侯丛哲,黄太胜,王华丽,朱琳   

  1. 山东大学第二医院妇科, 山东 济南 250033
  • 发布日期:2021-11-11
  • 通讯作者: 朱琳. E-mail:zl-emtf@163.com
  • 基金资助:
    山东省重点研发计划(公益类专项)项目(2019GSF108119);济南市科学技术发展计划第七批项目(医疗卫生)(201907008)

Correlation among PAX1 methylation, high-grade cervical intraepithelial lesions and HR-HPV classification

LIANG Tingting, YANG Yongxia, HOU Congzhe, HUANG Taisheng, WANG Huali, ZHU Lin   

  1. Department of Gynecology, The Second Hospital of Shandong University, Jinan 250033, Shandong, China
  • Published:2021-11-11

PDF (PC)

279

摘要： 目的 分析397例患者中PAX1基因甲基化与宫颈高级别上皮内病变及高危型人乳头瘤病毒(HR-HPV)分型的关联性。 方法 2019年8月至2020年10月于山东大学第二医院行宫颈薄层液基细胞学检查(TCT)和HR-HPV DNA检查的女性中,选取TCT结果异常:≥意义不明的非典型鳞状细胞(ASCUS)和/或HR-HPV阳性的患者397例;根据2020年阴道镜应用的中国专家共识,转诊阴道镜,阴道镜检查结果异常者行定点活检病理检查;RT-qPCR检测患者的PAX1甲基化程度。 结果 病理分级为宫颈上皮内瘤变3级和宫颈癌(CIN3+)(55例)与正常/宫颈炎(72例)、CIN1(36例)、CIN2(72例)患者比较,PAX1甲基化水平分别为18.64(4.01, 20.83)和20.22(19.24, 20.84)、20.33(19.65, 21.00)、20.43(15.31, 21.08),CIN3+患者PAX1甲基化程度高于正常/CIN1/CIN2的患者,差异有统计学意义(Z值分别为3.03、2.65、3.06;P值分别为0.002、0.008、0.002);HPV16阳性患者(89例)与12型高危型HPV(12HR-HPV)阳性的患者(174例)比较,PAX1甲基化水平分别为19.72(10.00, 20.91)和21.00(18.97, 21.02),前者PAX1甲基化程度高于后者,差异有统计学意义(Z=2.736,P=0.006);TCT诊断为ASCUS的患者, 病理分级CIN2+(23例)与正常/CIN1(19例)比较,PAX1甲基化水平分别为20.47(19.33, 21.18)和18.03(11.2, 20.82),前者PAX1甲基化程度高于后者,差异有统计学意义(Z=2.45, P=0.014)。 结论 PAX1甲基化程度与宫颈高级别上皮内病变及感染的HPV型别有关联,PAX1甲基化检测有助于早期识别CIN3+及ASCUS中的宫颈高级别病变,帮助ASCUS的分流、减少阴道镜的转诊率。

关键词: PAX1甲基化, 宫颈癌, 宫颈上皮内病变, 意义不明的非典型鳞状细胞, 高危型HPV

Abstract: Objective To analyze the correlation among PAX1 methylation, cervical high-grade intraepithelial neoplasia and the type of high-risk HPV. Methods From Aug. 2019 to Oct. 2020, women who underwent thinprep cytologic test(TCT)and high-risk human papillomavirus(HR-HPV)DNA examinations in The Second Hospital of Shandong University were screened, and 397 patients with abnormal TCT results: ≥atypical squamous cells of undetermined significance(ASCUS), and/or HR-HPV positive were selected. According to the consensus of Chinese experts on the application of colposcopy in 2020, those with abnormal colposcopy results should also undergo biopsy and RT-qPCR to detect PAX1 methylation. Results Pathological grade of 397 patients were CIN3+(55 cases), normal/cervicitis(72 cases), CIN1(36 cases), and CIN2(72 cases); their PAX1 methylation levels were 18.64(4.01, 20.83), 20.22(19.24, 20.84), 20.33(19.65, 21.00), and 20.43(15.31, 21.08). The PAX1 methylation level of CIN3+ patients was higher than that of normal/CIN1/CIN2 patients(Z=3.03, 2.65, 3.06; P=0.002, 0.008, 0.002). The PAX1 methylation levels of HPV16-positive patients(89 cases)and type 12 high-risk HPV(12HR-HPV)-positive patients(174 cases)were 19.72(10.00, 20.91)and 21.00(18.97, 21.02)(Z=2.736, P=0.006). Among ASCUS patients, the methylation levels of CIN2+(23 cases)and normal/CIN1(19 cases)were 20.47(19.33, 21.18)and 18.03(11.2, 20.82)(Z=2.45, P=0.014). Conclusion The degree of PAX1 methylation is related to high-grade cervical intraepithelial lesions and HPV types. PAX1 methylation detection would benefit the early identification of CIN3+ and high-grade cervical lesions in ASCUS, help the diversion of ASCUS, and reduce the referral rate of colposcopy.

Key words: PAX1 methylation, Cervical cancer, Cervical intraepithelial lesions, Atypical squamous cells of undetermined significance, High-risk HPV

中图分类号: 

  • R737.33
[1] Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries [J]. CA Cancer J Clin, 2018, 68(6): 394-424.
[2] zur Hausen H. Papillomaviruses and cancer: from basic studies to clinical application [J]. Nat Rev Cancer, 2002, 2(5): 342-350.
[3] MacLaughlin KL, Jacobson RM, Radecki BC, et al. Trends over time in pap and pap-HPV cotesting for cervical cancer screening[J]. J Womens Health(Larchmt). 2019,28(2):244-249.
[4] Nkwabong E, Laure Bessi Badjan I, Sando Z.Pap smear accuracy for the diagnosis of cervical precancerous lesions [J]. Trop Doct, 2019, 49(1): 34-39.
[5] Narkcham S, Mody DR, Jones A, et al. Rescreening of high-risk HPV positive Papanicolaou tests initially screened as negative is a low yield procedure in the era of HPV genotyping [J]. J Am Soc Cytopathol, 2021, 19: S2213-2945. doi: 10.1016/j.jasc.2021.05.002.
[6] Er Güneri S, ?瘙塁en S. Womens experiences after abnormal Pap smear results: a qualitative study [J]. J Psychosom Obstet Gynaecol, 2020, 41(1): 22-29.
[7] Hoda RS, Finer EB, Arpin RN, et al. Risk of malignancy in the categories of the Papanicolaou Society of Cytopathology system for reporting pancreaticobiliary cytology [J]. J Am Soc Cytopathol, 2019, 8(3): 120-127.
[8] Bhatla N, Singhal S. Primary HPV screening for cervical cancer [J]. Best Pract Res Clin Obstet Gynaecol, 2020, 65: 98-108. doi: 10.1016/j.bpobgyn.2020.02.008.
[9] Pista A, Costa C, Saldanha C, et al. Budget impact analysis of cervical cancer screening in Portugal: comparison of cytology and primary HPV screening strategies [J]. BMC Public Health, 2019, 19(1): 235. doi: 10.1186/s12889-019-6536-4.
[10] Zhang Y, Wang J, Zhang R, et al. Application value of detection of high-risk HPV infection in early cervical cancer patients in disease diagnosis and prognosis evaluation [J]. Clin Lab, 2020, 66(12). doi: 10.7754/Clin.Lab.2020.200245.
[11] Pruski D, Millert-Kalinska S, Lewek A, et al. Sensitivity and specificity of HR HPV E6/E7 mRNA test in detecting cervical squamous intraepithelial lesion and cervical cancer [J]. BMC Cancer, 2019, 90(2):66-71.
[12] 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.
[13] El Aliani A, El-Abid H, El 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.
[14] Kelly H, Benavente Y, Pavon MA, et al. Performance of DNA methylation assays for detection of high-grade cervical intraepithelial neoplasia(CIN2+): a systematic review and meta-analysis [J]. Bri J Cancer, 2019, 121(11): 954-965.
[15] Fang C, Wang SY, Liou YL, et al. The promising role of PAX1(aliases: HUP48, OFC2)gene methylation in cancer screening [J]. Mol Genet Genomic Med, 2019, 7(3): e506. doi: 10.1002/mgg3.506.
[16] 李明珠, 魏丽惠. 甲基化检测在宫颈癌诊治中的意义[J].现代妇产科进展,2019, 28(9): 704-705. LI Mingzhu, WEI Lihui. Significance of methylation detection in the diagnosis and treatment of cervical cancer [J]. Progress in Obstetrics and Gynecology, 2019, 28(9): 704-705.
[17] Li B, Guo R, Lai T, et al. The application of PAX1 methylation detection and HPV E6/E7 mRNA detection in cervical cancer screening [J]. J Obstet Gynaecol Res, 2021, 47(8): 2720-2728.
[18] Dvorská D, Brany D, Nagy B, et al. Aberrant methylation status of tumour suppressor genes in ovarian cancer tissue and paired plasma samples [J]. Int J Mol Sci, 2019, 20(17): 4119. doi: 10.3390/ijms20174119.
[19] 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.
[20] Wang M, Hou B, Wang X, et al. Diagnostic value of high-risk human papillomavirus viral load on cervical lesion assessment and ASCUS triage [J]. Cancer Med, 2021, 10(7): 2482-2488.
[21] Oranratanaphan S, Kobwitaya K, Termrungruanglert W, et al. Value of CCNA1 promoter methylation in triaging ASC-US cytology [J]. Asian Pac J Cancer Prev, 2020, 21(2): 473-477.
[22] Curry SJ, Krist AH, Owens DK, et al. Screening for cervical cancer: us preventive services task force recommendation statement [J]. JAMA, 2018, 320(7): 674-686.
[23] Sammarco ML, Tamburro M, Pulliero A, et al. Human papillomavirus infections, cervical cancer and microRNAs: an overview and implications for public health [J]. Microrna, 2020, 9(3): 174-186.
[24] Gutnik H, Kastelic P, Oštrbenk Valen cak A, et al. Histomorphologic assessment and distribution of high-risk human papillomavirus(HPV)types in cervical high-grade squamous intraepithelial lesions with unusual histomorphologic features [J]. Virchows Arch, 2020, 476(2): 251-260.
[25] Torres-Poveda K, Ruiz-Fraga I, Madrid-Marina V, et al. High risk HPV infection prevalence and associated cofactors: a population-based study in female ISSSTE beneficiaries attending the HPV screening and early detection of cervical cancer program [J]. BMC Cancer, 2019, 19(1): 1205. doi: 10.1186/s12885-019-6388-4.
[26] 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. WANG Wenjie, YU Minhong, FAN Shizhen, et al. A correlation between human papillomavirus(HPV)type and methylation of SOX1 and PAX1 genes [J]. Chinese Journal Laboratory Diagnosis, 2020, 4(8): 1353-1356.
[1] 修德健,高正文,宋婷婷,崔楠,崔静,孙健平. 生物信息学方法分析与宫颈癌有关联的基因[J]. 山东大学学报 (医学版), 2022, 60(10): 99-109.
[2] 陈泉材,韩赛,刘露,孙雨,尤学武,张俊华,张友忠. CDC7、MCM4在105例宫颈病变组织中的表达及意义[J]. 山东大学学报 (医学版), 2022, 60(1): 34-39.
[3] 王璐,赵新蕊,朱琳. 25例早期宫颈癌无瘤化免举宫腹腔镜子宫切除术临床效果[J]. 山东大学学报 (医学版), 2021, 59(6): 76-80.
[4] 杨佳欣,沈铿,王遥. 妇科恶性肿瘤保留生育功能治疗的现状与展望[J]. 山东大学学报 (医学版), 2018, 56(5): 1-7.
[5] 陈颖,周小青,齐眉,张魏芳,刘娟,赵蔚明. 干扰PRPS2基因表达对宫颈癌细胞生物学特性的影响[J]. 山东大学学报 (医学版), 2018, 56(2): 9-13.
[6] 王永,姜晨,周士英,杨晓玫. IQ结构域GTP酶激活蛋白3表达对宫颈癌细胞增殖和转移的影响[J]. 山东大学学报 (医学版), 2018, 56(10): 103-109.
[7] 丁长宽,陈健行. 蛋白酶体抑制剂硼替佐米联合顺铂对宫颈癌细胞增殖的影响[J]. 山东大学学报 (医学版), 2018, 56(1): 70-75.
[8] 刘京康,杨建勇,孟丽华,姜洁. 血清miR-17-92簇在HPV阳性宫颈癌中的早期诊断价值[J]. 山东大学学报（医学版）, 2017, 55(5): 86-90.
[9] 孙泽雨,陈颖,林家香,刘娟,赵蔚明. 磷脂酰肌醇-4-磷酸酶II型对宫颈癌细胞增殖及凋亡的影响[J]. 山东大学学报（医学版）, 2017, 55(11): 1-6.
[10] 王雅芬,杨勇霞,刘娅,马德美,朱琳. 宫颈细胞学阴性且高危型人乳头瘤病毒阳性人群的分流方法[J]. 山东大学学报（医学版）, 2016, 54(8): 69-71.
[11] 彭慧,何君梅,苏雪莲. 血清循环miR-375检测对宫颈癌早期诊断及术后监测的意义[J]. 山东大学学报（医学版）, 2016, 54(3): 68-71.
[12] 杜义江, 肖长义, 叶红, 汤桂成, 黎家华. CaSki细胞内HPVL1蛋白的表达[J]. 山东大学学报（医学版）, 2015, 53(3): 17-21.
[13] 冯建丽, 董淑云. 宫颈癌根治术后淋巴囊肿的护理[J]. 山东大学学报（医学版）, 2014, 52(S2): 141-141.
[14] 李贺群, 聂春兰. 宫颈癌合并肺肾转移1例[J]. 山东大学学报（医学版）, 2014, 52(S1): 119-119.
[15] 袁首道, 王凤琴, 张娇, 赵蔚明, 陈健行. 宫颈腺癌细胞与宫颈鳞癌细胞蛋白表达差异的质谱分析[J]. 山东大学学报（医学版）, 2014, 52(8): 14-21.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
[1] 郑敏,郝跃伟,刘雪平,赵婷婷. 血小板膜糖蛋白Ibα基因HPA-2、Kozak序列多态性与脑梗死的相关性研究[J]. 山东大学学报(医学版), 2008, 46(3): 292 -295 .
[2] 张杰,李振华,孙晋浩,暴丽华,刘岳鹏. 恒定磁场对Schwann细胞氧化损伤的保护作用[J]. 山东大学学报(医学版), 2007, 45(3): 229 -232 .
[3] 王术芹,齐 峰,吴剑波,孙宝柱. 罗哌卡因对大鼠离体主动脉收缩作用的钙离子调节机制[J]. 山东大学学报(医学版), 2008, 46(8): 773 -776 .
[4] 滕学仁,赵永生,胡光亮,周伦,李建民 . 两种方法保存同种异体髌腱移植重建膝关节交叉韧带的光镜电镜观察[J]. 山东大学学报(医学版), 2008, 46(10): 945 -950 .
[5] 袁吴敏,赵志伦,王洁贞 . 吸烟和饮酒与颅内肿瘤关系的Meta分析[J]. 山东大学学报(医学版), 2006, 44(11): 1146 -1149 .
[6] 焦芳芳,刘世青,李飞,李长生,王琴,孙青,鹿伟 . 化瘀理肺方对大鼠肺间质纤维化时Smad7和TGF-β表达的影响[J]. 山东大学学报(医学版), 2007, 45(10): 1054 -1058 .
[7] 赵瑛，颜磊，张辉，于鹏，李明江，赵兴波. 精子相关抗原9在卵巢浆液性上皮肿瘤中的表达[J]. 山东大学学报(医学版), 2012, 50(2): 98 .
[8] 方英立,马玉燕,刘锡梅,周文 . 急诊剖宫产患者围手术期替硝唑合理应用[J]. 山东大学学报(医学版), 2007, 45(10): 995 .
[9] 姜红菊,李润智,王营,徐冬梅,张梅,张运,李继福 . 冠状动脉粥样硬化斑块形态及介入治疗与MMP-9的关系[J]. 山东大学学报(医学版), 2008, 46(10): 966 -970 .
[10] 李明霞,王学禹 . 儿童急性播散性脑脊髓炎31例临床与MRI特点[J]. 山东大学学报(医学版), 2008, 46(8): 828 -830 .
版权所有 © 2018 《山东大学学报(医学版)》编辑部　
地址:山东大学科技期刊社（济南市历城区山大南路27号山东大学中心校区明德楼B座721室） 电话: 0531-88366918 E-mail: xbyxb@sdu.edu.cn
本系统由北京玛格泰克科技发展有限公司设计开发