切换至 "中华医学电子期刊资源库"
高级检索
中华妇幼临床医学杂志(电子版)

中华妇幼临床医学杂志(电子版) ›› 2021, Vol. 17 ›› Issue (01) : 23 -29. doi: 10.3877/cma.j.issn.1673-5250.2021.01.004

所属专题： 文献；

专题论坛

FAM19A4基因启动子甲基化检测在宫颈癌及其癌前病变筛查的研究
何路路, 布俏雯, 罗家祺, 辜佳婷, 罗喜平†()   
  • 收稿日期:2020-09-30 修回日期:2021-01-03 出版日期:2021-02-01
  • 通信作者: 罗喜平

Current research status of methylation quantification of FAM19A4 gene promoter in cervical cancer and its precancerous lesion screening

Lulu He, Qiaowen Bu, Jiaqi Luo, Jiating Gu, Xiping Luo†()   

  • Received:2020-09-30 Revised:2021-01-03 Published:2021-02-01
  • Corresponding author: Xiping Luo
  • Supported by:
    Project of Science and Technology Department of Guangdong Province(2017ZC0317); Science and Technology Plan of Guangzhou(202002030174)
全文 ( ) 下载PDF ( ) 导出引用
引用本文：

何路路, 布俏雯, 罗家祺, 辜佳婷, 罗喜平. FAM19A4基因启动子甲基化检测在宫颈癌及其癌前病变筛查的研究[J]. 中华妇幼临床医学杂志(电子版), 2021, 17(01): 23-29.

Lulu He, Qiaowen Bu, Jiaqi Luo, Jiating Gu, Xiping Luo. Current research status of methylation quantification of FAM19A4 gene promoter in cervical cancer and its precancerous lesion screening[J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2021, 17(01): 23-29.

宫颈癌是最常见的妇科恶性肿瘤之一。目前人乳头瘤病毒(HPV)检测及细胞学检查是宫颈癌及其癌前病变(CCPL)的主要筛查手段。由于上述传统筛查方法，仍然存在对CCPL漏诊的风险，因此寻找有效识别CCPL的特异性分子标志物，具有重要临床意义。对具有序列相似性家族19成员A4(FAM19A4)基因启动子甲基化定量检测，可有效检出CCPL组织，较传统筛查方法有较高特异度，有望成为CCPL筛查的特异性分子标志物。笔者拟就FAM19A4基因启动子甲基化定量检测，在CCPL筛查中应用的最新研究现状进行阐述，旨在为进一步推进CCPL筛查方法的开发，提供思路。

关键词: 宫颈肿瘤, 癌前状态, 分子靶向治疗, 分子标志物, DNA甲基化, FAM19A4, 启动区, 遗传, 女(雌)性

Cervical cancer is one of the most common gynecologic malignancies. At present, human papillomavirus (HPV) and cytological test are the main screening methods for cervical cancer and its precancerous lesions (CCPL). As the above traditional screening methods have the risk of missed diagnosis of CCPL, it is of great significance to find specific molecular markers that can effectively identify CCPL. Methylation quantification of family with sequence similarity 19 member A4 (FAM19A4) gene promoter can effectively detect CCPL tissues, with higher specificity than traditional screening methods, and is expected to be a specific molecular marker for screening CCPL. The authors intend to describe methylation quantification of FAM19A4 gene promoter in CCPL screening in order to provide ideas for further promoting the development of CCPL screening methods.

Key words: Uterine cervical neoplasms, Precancerous conditions, Molecular targeted therapy, Molecular markers, DNA methylation, FAM19A4, Promoter regions, genetic, Female
[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. DOI: 10.3322/caac.21492.
[2]
王临虹，赵更力. 中国子宫颈癌综合防控指南[J]. 中国妇幼健康研究，2018, 29(1): 1-3. DOI: 10.3969/j.issn.1673-5293.2018.01.001.
[3]
Vink FJ, Lissenberg-Witte BI, Meijer CJLM, et al. FAM19A4/miR124-2 methylation analysis as a triage test for HPV-positive women: cross-sectional and longitudinal data from a Dutch screening cohort[J]. Clinc Microbiol Infect, 2020: S1198-743X(20)30163-4. DOI: 10.1016/j.cmi.2020.03.018.
[4]
Koliopoulos G, Nyaga VN, Santesso N, et al. Cytology versus HPV testing for cervical cancer screening in the general population[J]. Cochrane Database Syst Rev, 2017, 8(8): CD008587. DOI: 10.1002/14651858.CD008587.pub2.
[5]
Bowden SJ, Lathouras K, Kyrgiou M. Can DNA methylation tests improve the accuracy of cervical screening？[J]. BJOG, 2021, 128(3): 515. DOI: 10.1111/1471-0528.16448.
[6]
布俏雯，张亮，王三锋，等. FAM19A4基因启动子甲基化检测在宫颈癌组织中的临床意义[J]. 实用医学杂志，2018, 34(9): 1541-1544, 1553. DOI: 10.3969/j.issn.1006-5725.2018.09.033.
[7]
De Strooper L, Berkhof J, Steenbergen R, et al. Cervical cancer risk in HPV-positive women after a negative FAM19A4/ mir124-2 methylation test: a post hoc analysis in the POBASCAM trial with 14 year follow-up[J]. Int J Cancer, 2018, 143(6): 1541-1548. DOI: 10.1002/ijc.31539.
[8]
De Strooper LMA, Meijer CJ, Berkhof J, et al. Methylation analysis of the FAM19A4 gene in cervical scrapes is highly efficient in detecting cervical carcinomas and advanced CIN2/3 lesions[J]. Cancer Prev Res (Phila), 2014, 7(12): 1251-1257. DOI: 10.1158/1940-6207.CAPR-14-0237.
[9]
Bao H, Zhang L, Wang L, et al. Significant variations in the cervical cancer screening rate in China by individual-level and geographical measures of socioeconomic status: a multilevel model analysis of a nationally representative survey dataset[J]. Cancer Med, 2018, 7(5): 2089-2100. DOI: 10.1002/cam4.1321.
[10]
Cuschieri K, Ronco G, Lorincz A, et al. Eurogin roadmap 2017: triage strategies for the management of HPV-positive women in cervical screening programs[J]. Int J Cancer, 2018, 143(4): 735-745. DOI: 10.1002/ijc.31261.
[11]
霍文婧，梁茂盛，韩存芝. 人乳头瘤病毒联合薄层液基细胞检查在子宫颈疾病筛查中的应用[J]. 肿瘤研究与临床，2016, 28(2): 103-106. DOI: 10.3760/cma.j.issn.1006-9801.2016.02.008.
[12]
赵君，赵媛. 液基细胞学与HPV分型联合检测对早期宫颈癌的筛查意义[J]. 实用癌症杂志，2018, 33(1): 143-146. DOI: 10.3969/j.issn.1001-5930.2018.01.044.
[13]
Lorincz AT. Virtues and weaknesses of DNA methylation as a test for cervical cancer prevention[J]. Acta Cytol, 2016, 60(6): 501-512. DOI: 10.1159/000450595.
[14]
Luttmer R, De Strooper LM, Berkhof J, et al. Comparing the performance of FAM19A4 methylation analysis, cytology and HPV16/18 genotyping for the detection of cervical (pre)cancer in high-risk HPV-positive women of a gynecologic outpatient population (COMETH study)[J]. Int J Cancer, 2016, 138(4): 992-1002. DOI: 10.1002/ijc.29824.
[15]
Vink FJ, Meijer C, Clifford GM, et al. FAM19A4/ miR124-2 methylation in invasive cervical cancer: a retrospective cross-sectional worldwide study[J]. Int J Cancer, 2019, 147(4): 1215-1221. DOI: 10.1002/ijc.32614.
[16]
Mac M, Moody CA. Epigenetic regulation of the human papillomavirus life cycle[J]. Pathogens, 2020, 9(6): 483. DOI: 10.3390/pathogens9060483.
[17]
Feng C, Dong J, Chang W, et al. The progress of methylation regulation in gene expression of cervical cancer[J]. Int J Genomics, 2018, 2018: 8260652. DOI: 10.1155/2018/8260652.
[18]
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]. Br J Cancer, 2019, 121(11): 954-965. DOI: 10.1038/s41416-019-0593-4.
[19]
Au Yeung CL, Tsang WP, Tsang TY, et al. HPV-16 E6 upregulation of DNMT1 through repression of tumor suppressor p53[J]. Oncol Rep, 2010, 24(6): 1599-1604. DOI: 10.3892/or_00001023.
[20]
Zhang J, Yang C, Wu C, et al. DNA methyltransferases in cancer: biology, paradox, aberrations, and targeted therapy[J]. Cancers (Basel), 2020，12(8): 2123. DOI: 10.3390/cancers12082123.
[21]
Steenbergen RD, Ongenaert M, Snellenberg S, et al. Methylation-specific digital karyotyping of HPV16E6E7-expressing human keratinocytes identifies novel methylation events in cervical carcinogenesis[J]. J Pathol, 2013, 231(1): 53-62. DOI: 10.1002/path.4210.
[22]
Bu Q, Wang S, Ma J, et al. The clinical significance of FAM19A4 methylation in high-risk HPV-positive cervical samples for the detection of cervical (pre)cancer in Chinese women[J]. BMC Cancer, 2018, 18(1): 1182. DOI: 10.1186/s12885-018-4877-5.
[23]
Jee B, Yadav R, Pankaj S, et al. Immunology of HPV-mediated cervical cancer: current understanding[J]. Int Rev Immunol, 2020: 1-20. DOI: 10.1080/08830185.2020.1811859.
[24]
Luttmer R, De Strooper LM, Steenbergen RD, et al. Management of high-risk HPV-positive women for detection of cervical (pre)cancer[J]. Expert Rev Mol Diagn, 2016, 16(9): 961-974. DOI: 10.1080/14737159.2016.1217157.
[25]
Tom TY, Emtage P, Funk WD, et al. TAFA: a novel secreted family with conserved cysteine residues and restricted expression in the brain[J]. Genomics, 2004, 83(4): 727-734. DOI: 10.1016/j.ygeno.2003.10.006.
[26]
Delfini M, Mantilleri A, Gaillard S, et al. TAFA4, a chemokine-like protein, modulates injury-induced mechanical and chemical pain hypersensitivity in mice[J]. Cell Rep, 2013, 5(2): 378-388. DOI: 10.1016/j.celrep.2013.09.013.
[27]
Wang W, Li T, Wang X, et al. FAM19A4 is a novel cytokine ligand of formyl peptide receptor 1 (FPR1) and is able to promote the migration and phagocytosis of macrophages[J]. Cell Mol Immunol, 2015, 12(5): 615-624. DOI: 10.1038/cmi.2014.61.
[28]
Shi X, Doycheva DM, Xu L, et al. Sestrin2 induced by hypoxia inducible factor1 alpha protects the blood-brain barrier via inhibiting VEGF after severe hypoxic-ischemic injury in neonatal rats[J]. Neurobiol Dis, 2016, 95: 111-121. DOI: 10.1016/j.nbd.2016.07.016.
[29]
Vink MA, Bogaards JA, van Kemenade FJ, et al. Clinical progression of high-grade cervical intraepithelial neoplasia: estimating the time to preclinical cervical cancer from doubly censored national registry data[J]. Am J Epidemiol, 2013, 178(7): 1161-1169. DOI: 10.1093/aje/kwt077.
[30]
Polman NJ, Snijders P, Kenter GG, et al. HPV-based cervical screening: rationale, expectations and future perspectives of the new Dutch screening programme[J]. Prev Med, 2019, 119: 108-117. DOI: 10.1016/j.ypmed.2018.12.021.
[31]
Katki HA, Schiffman M, Castle PE, et al. Five-year risks of CIN 3+ and cervical cancer among women who test Pap-negative but are HPV-positive[J]. J Low Genit Tract Dis, 2013, 17(5 Suppl 1): S56-S63. DOI: 10.1097/LGT.0b013e318285437b.
[32]
Bruinsma FJ, Quinn MA. The risk of preterm birth following treatment for precancerous changes in the cervix: a systematic review and Meta-analysis[J]. BJOG, 2011, 118(9): 1031-1041. DOI: 10.1111/j.1471-0528.2011.02944.x.
[33]
Kremer WW, Berkhof J, Bleeker MC, et al. Role of FAM19A4/miR124-2 methylation analysis in predicting regression or nonregression of CIN2/3 lesions: a protocol of an observational longitudinal cohort study[J]. BMJ Open, 2019, 9(7): e29017. DOI: 10.1136/bmjopen-2019-029017.
[34]
De Strooper LMA, Verhoef VMJ, Berkhof J, et al. Validation of the FAM19A4/mir124-2 DNA methylation test for both lavage-and brush-based self-samples to detect cervical (pre)cancer in HPV-positive women[J]. Gynecol Oncol, 2016, 141(2): 341-347. DOI: 10.1016/j.ygyno.2016.02.012.
[35]
Hesselink AT, Heideman DAM, Steenbergen RDM, et al. Methylation marker analysis of self-sampled cervico-vaginal lavage specimens to triage high-risk HPV-positive women for colposcopy[J]. Int J Cancer, 2014, 135(4): 880-886. DOI: 10.1002/ijc.28723.
[36]
Steenbergen RDM, Snijders PJF, Heideman DAM, et al. Clinical implications of (epi)genetic changes in HPV-induced cervical precancerous lesions[J]. Nat Rev Cancer, 2014, 14(6): 395-405. DOI: 10.1038/nrc3728.
[37]
Tainio K, Athanasiou A, Tikkinen K, et al. Clinical course of untreated cervical intraepithelial neoplasia grade 2 under active surveillance: systematic review and Meta-analysis[J]. BMJ, 2018, 360: k499. DOI: 10.1136/bmj.k499.
[38]
伍恒英，彭苏珺，布俏雯，等. FAM19A4基因启动子甲基化在高危型HPV阴性宫颈癌诊断中的作用[J]. 实用医学杂志，2019, 35(5): 683-687. DOI: 10.3969/j.issn.1006-5725.2019.05.002.
[39]
Kurokawa T, Yoshida Y, Iwanari O, et al. Implementation of primary HPV testing in Japan[J]. Mol Clin Oncol, 2020, 13(4): 22. DOI: 10.3892/mco.2020.2092.
[1] 马敏榕, 李聪, 周勤. 宫颈癌治疗研究现状[J]. 中华妇幼临床医学杂志(电子版), 2023, 19(05): 497-504.
[2] 林昌盛, 战军, 肖雪. 上皮性卵巢癌患者诊疗中基因检测及分子靶向药物治疗[J]. 中华妇幼临床医学杂志(电子版), 2023, 19(05): 505-510.
[3] 王璐, 樊杨. 子宫内膜癌相关生物标志物研究现状[J]. 中华妇幼临床医学杂志(电子版), 2023, 19(05): 511-516.
[4] 顾娟, 孙擎擎, 胡方方, 曹义娟, 祁玉娟. 子宫内膜容受性检测改善胚胎反复种植失败患者妊娠结局的临床应用[J]. 中华妇幼临床医学杂志(电子版), 2023, 19(05): 582-587.
[5] 周东杰, 蒋敏, 范海瑞, 高玲玲, 孔祥, 卢丹, 王丽萍. 非编码RNA在卵泡发育成熟中作用及其机制的研究现状[J]. 中华妇幼临床医学杂志(电子版), 2023, 19(04): 387-393.
[6] 陈荟竹, 郭应坤, 汪昕蓉, 宁刚, 陈锡建. 上皮性卵巢癌"二元论模型"的分子生物学研究现状[J]. 中华妇幼临床医学杂志(电子版), 2023, 19(04): 394-402.
[7] 韩春颖, 王婷婷, 李艳艳, 朴金霞. 子宫内膜癌患者淋巴管间隙浸润预测因素研究现状[J]. 中华妇幼临床医学杂志(电子版), 2023, 19(04): 403-409.
[8] 娄丽丽, 刘瀚旻. 儿童哮喘易感基因及表观遗传学研究现状[J]. 中华妇幼临床医学杂志(电子版), 2023, 19(03): 249-255.
[9] 林凌, 李佩, 赵玮. 牛牙样牙发病机制的研究进展[J]. 中华口腔医学研究杂志(电子版), 2023, 17(02): 75-80.
[10] 徐瑜杰, 赵国栋. 晚期胃癌治疗方法的研究进展和挑战[J]. 中华普外科手术学杂志(电子版), 2023, 17(04): 451-455.
[11] 陆闻青, 陈昕怡, 任雪飞. 遗传代谢病儿童肝移植受者术后生活质量调查研究[J]. 中华移植杂志(电子版), 2023, 17(05): 287-292.
[12] 张小康, 张伟, 赵彦宗, 李卫平, 常鹏程, 史志龙. 先天性肾上腺皮质增生症合并肾上腺肿瘤手术治疗一例报告[J]. 中华腔镜泌尿外科杂志(电子版), 2023, 17(03): 288-290.
[13] 张瑞琪, 张丽娟, 孙斌. 甲状腺相关性眼病表观遗传学的研究进展[J]. 中华眼科医学杂志(电子版), 2023, 13(04): 226-230.
[14] 刘迎, 尹嫚, 杨林青, 王云飞. 子宫颈浸润性复层产黏液的癌的诊断学特征并文献复习[J]. 中华诊断学电子杂志, 2023, 11(03): 173-177.
[15] 杨海华, 袁景林, 周晓梅, 牛军伟. RNF213基因突变所致烟雾病一家系病例临床分析并文献复习[J]. 中华脑血管病杂志(电子版), 2023, 17(05): 495-498.
阅读次数
全文


摘要

版权所有 中华医学会 中华医学电子音像出版社有限责任公司  京ICP备14006079号-1  网络出版服务许可证：(署)网出证(京)字第075号