切换至 "中华医学电子期刊资源库"

中华乳腺病杂志(电子版) ›› 2025, Vol. 19 ›› Issue (01) : 49 -53. doi: 10.3877/cma.j.issn.1674-0807.2025.01.009

综述

特异性DNA 甲基化位点在乳腺癌中的研究进展
郭健冉1,2, 解磐磐3, 王松2, 谭明真2, 付波2,()   
  1. 1.250000 济南大学生物科学与技术学院
    2.252000 聊城市人民医院山东省医药卫生衰老干预与主动健康精准医学重点实验室/精准生物医学重点实验室
    3.252000 聊城市人民医院乳腺甲状腺外科
  • 收稿日期:2024-08-19 出版日期:2025-02-01
  • 通信作者: 付波
  • 基金资助:
    山东省自然科学基金资助项目(ZR2022MH272)山东省中医药科技资助项目(M-2022122)聊城市重点研发资助项目(2022YDSF24)

Research progress of specific DNA methylation sites in breast cancer

Jianran Guo, Panpan Xie, Song Wang, Mingzhen Tan, Bo Fu()   

  • Received:2024-08-19 Published:2025-02-01
  • Corresponding author: Bo Fu
引用本文:

郭健冉, 解磐磐, 王松, 谭明真, 付波. 特异性DNA 甲基化位点在乳腺癌中的研究进展[J/OL]. 中华乳腺病杂志(电子版), 2025, 19(01): 49-53.

Jianran Guo, Panpan Xie, Song Wang, Mingzhen Tan, Bo Fu. Research progress of specific DNA methylation sites in breast cancer[J/OL]. Chinese Journal of Breast Disease(Electronic Edition), 2025, 19(01): 49-53.

DNA 甲基化作为一种常见的表观遗传修饰,可以在不改变DNA 序列的情况下调节基因的表达水平。 在乳腺癌中,DNA 甲基化模式异常主要表现为全基因组范围的低甲基化与特异性位点的高甲基化,且与乳腺癌的发生、发展和诊疗密切相关。 特定位点的DNA 甲基化水平可以反映乳腺癌的进展,为乳腺癌精准检测提供潜在的分子靶点。 外周血中的循环肿瘤DNA(ctDNA)保留了原发肿瘤的表观遗传信息,在此基础上联合多种特异性甲基化位点检测,可进一步降低采样风险、提高乳腺癌检测效率。 本文综述了DNA 甲基化在乳腺癌发生、发展、转移中的作用,以及在乳腺癌早期诊断、治疗监测及预后评估中的研究进展,重点探讨其在非侵入性检测中的临床应用潜力,为优化乳腺癌诊疗策略及提高患者生存率提供参考。

表1 乳腺癌特异性DNA 甲基化位点
[1]
Siegel RL,Miller KD, Wagle NS, et al. Cancer statistics, 2023[J].CA Cancer J Clin, 2023, 73(1):17-48.
[2]
Fakhri N,Chad MA, Lahkim M, et al. Risk factors for breast cancer in women: an update review[J]. Med Oncol, 2022, 39(12): 197.
[3]
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.
[4]
Burstein HJ,Curigliano G, Thürlimann B, et al. Customizing local and systemic therapies for women with early breast cancer: the St. Gallen International Consensus Guidelines for treatment of early breast cancer 2021[J]. Ann Oncol, 2021, 32(10): 1216-1235.
[5]
Li J,Sun D, Pu W, et al. Circular RNAs in cancer: biogenesis,function, and clinical significance[J]. Trends Cancer, 2020, 6(4):319-336.
[6]
Kok VC,Yu CC. Cancer-derived exosomes: their role in cancer biology and biomarker development[J]. Int J Nanomedicine, 2020, 15: 8019-8036.
[7]
Pessoa LS,Heringer M, Ferrer VP. ctDNA as a cancer biomarker: a broad overview[J]. Crit Rev Oncol Hematol, 2020, 155: 103109.
[8]
Manoochehri M,Borhani N, Gerha··user C, et al. DNA methylation biomarkers for noninvasive detection of triple-negative breast cancer using liquid biopsy[J]. Int J Cancer, 2023, 152(5): 1025-1035.
[9]
Fiorito G,Caini S, Palli D, et al. DNA methylation-based biomarkers of aging were slowed down in a two-year diet and physical activity intervention trial: the DAMA study[J]. Aging Cell, 2021, 20(10):e13439.
[10]
Cao YN,Li QZ, Liu YX. Discovered key CpG sites by analyzing DNA methylation and gene expression in breast cancer samples[J]. Front Cell Dev Biol, 2022, 10: 815843.
[11]
Nishiyama A,Nakanishi M. Navigating the DNA methylation landscape of cancer[J]. Trends Genet, 2021, 37(11): 1012-1027.
[12]
Skvortsova K,Stirzaker C, Taberlay P. The DNA methylation landscape in cancer[J]. Essays Biochem, 2019, 63(6): 797-811.
[13]
Dor Y,Cedar H. Principles of DNA methylation and their implications for biology and medicine[J]. Lancet, 2018, 392(10149): 777-786.
[14]
Dao J,Conway PJ, Subramani B, et al. Using cfDNA and ctDNA as oncologic markers: a path to clinical validation[J]. Int J Mol Sci,2023, 24(17): 13219.
[15]
Song P,Wu LR, Yan YH, et al. Limitations and opportunities of technologies for the analysis of cell-free DNA in cancer diagnostics[J].Nat Biomed Eng, 2022, 6(3): 232-245.
[16]
Koch A,Joosten SC, Feng Z, et al. Analysis of DNA methylation in cancer: location revisited[J]. Nat Rev Clin Oncol, 2018, 15(7):459-466.
[17]
Nishimura R, Osako T, Okumura Y, et al. An evaluation of lymphovascular invasion in relation to biology and prognosis according to subtypes in invasive breast cancer[J]. Oncol Lett,2022,24(2):245.
[18]
刘子天.磁共振成像在乳腺癌诊断中的应用进展[J]. 影像研究与医学应用, 2020, 4(11): 76-77.
[19]
Hing JX,Mok CW, Tan PT, et al. Clinical utility of tumour marker velocity of cancer antigen 15-3(CA15-3) and carcinoembryonic antigen(CEA) in breast cancer surveillance[J]. Breast, 2020, 52: 95-101.
[20]
Martisova A,Holcakova J, Izadi N, et al. DNA methylation in solid tumors: functions and methods of detection[J]. Int J Mol Sci, 2021,22(8): 4247.
[21]
Chen Z,Zhang Y. Role of mammalian DNA methyltransferases in development[J]. Annu Rev Biochem, 2020, 89(1): 135-158.
[22]
Guil S,Esteller M. PRC2 loss and DNMT inhibition boost viral mimicry in cancer[J]. Cancer Discov, 2022, 12(9): 2020-2022.
[23]
Janostiak R, Vyas M, Cicek AF, et al. Loss of c-KIT expression in breast cancer correlates with malignant transformation of breast epithelium and is mediated by KIT gene promoter DNA hypermethylation[J]. Exp Mol Pathol, 2018, 105(1): 41-49.
[24]
Angeloni A,Bogdanovic O. Enhancer DNA methylation: implications for gene regulation[J]. Essays Biochem, 2019, 63(6): 707-715.
[25]
Tourancheau A,Mead EA, Zhang XS, et al. Discovering multiple types of DNA methylation from bacteria and microbiome using nanopore sequencing[J]. Nat Methods, 2021, 18(5): 491-498.
[26]
Law PP,Holland ML. DNA methylation at the crossroads of gene and environment interactions[J]. Essays Biochem, 2019, 63(6): 10-15.
[27]
Mattei AL,Bailly NB, Meissner A. DNA methylation: a historical perspective[J]. Trends Genet, 2022, 38(7): 3-14.
[28]
Liu H,Song Y, Qiu H, et al. Downregulation of FOXO3a by DNMT1 promotes breast cancer stem cell properties and tumorigenesis[J]. Cell Death Differ, 2020, 27(3): 966-983.
[29]
Liu BW,Sun N, Lin H, et al. The p53/ZEB1-PLD3 feedback loop regulates cell proliferation in breast cancer[J]. Cell Death Dis, 2023,14(11): 751.
[30]
Wu G,Fan Z, Li X. CENPA knockdown restrains cell progression and tumor growth in breast cancer by reducing PLA2R1 promoter methylation and modulating PLA2R1/HHEX axis[J]. Cell Mol Life Sci, 2024, 81(1): 27.
[31]
Britt KL,Cuzick J, Phillips KA. Key steps for effective breast cancer prevention[J]. Nat Rev Cancer, 2020, 20(8): 417-436.
[32]
Wong KK.DNMT1: a key drug target in triple-negative breast cancer[J]. Semin Cancer Biol, 2021, 72: 198-213.
[33]
Mendaza S, Ulazia-Garmendia A, Monreal-Santesteban I, et al.ADAM12 is a potential therapeutic target regulated by hypomethylation in triple-negative breast cancer[J]. Int J Mol Sci, 2020, 21(3): 903.
[34]
Wang C,Zhao N, Yuan L, et al. Computational detection of breast cancer invasiveness with DNA methylation biomarkers [J]. Cells,2020, 9(2): 326.
[35]
Guo Y,Pakneshan P, Gladu J,et al. Regulation of DNA methylation in human breast cancer. Effect on the urokinase-type plasminogen activator gene production and tumor invasion[J]. J Biol Chem,2002,277(44):41571-41579.
[36]
Liu Y, Jin X, Li Y,et al. DNA methylation of claudin-6 promotes breast cancer cell migration and invasion by recruiting MeCP2 and deacetylating H3Ac and H4Ac[J]. J Exp Clin Cancer Res, 2016, 35:120.
[37]
Ma L,Li C,Yin H, et al. The mechanism of DNA methylation and miRNA in breast cancer[J]. Int J Mol Sci, 2023, 24(11): 9360.
[38]
Wang T,Li P, Qi Q, et al. A multiplex blood-based assay targeting DNA methylation in PBMCs enables early detection of breast cancer[J]. Nat Commun, 2023, 14(1): 4724.
[39]
Griess B,Klinkebiel D, Kueh A, et al. Association ofSOD3 promoter DNA methylation with its down-regulation in breast carcinomas[J].Epigenetics, 2020, 15(12): 1325-1335.
[40]
Kresovich JK,Gann PH, Erdal S, et al. Candidate gene DNA methylation associations with breast cancer characteristics and tumor progression[J]. Epigenomics, 2018, 10(4):3-15.
[41]
Lin RK,Su CM,Lin SY,et al. Hypermethylation of TMEM240 predicts poor hormone therapy response and disease progression in breast cancer[J]. Mol Med, 2022, 28(1): 67.
[42]
Fu D,Ren C, Tan H, et al. Sox17 promoter methylation in plasma DNA is associated with poor survival and can be used as a prognostic factor in breast cancer[J]. Medicine (Baltimore), 2015, 94(11):e637.
[43]
Li D,Zhao W, Zhang X, et al. NEFM DNA methylation correlates with immune infiltration and survival in breast cancer[J]. Clin Epigenetics,2021, 13(1): 112.
[44]
Pedersen CA,Cao MD,Fleischer T,et al. DNA methylation changes in response to neoadjuvant chemotherapy are associated with breast cancer survival[J]. Breast Cancer Res, 2022, 24: 43.
[45]
Antonios PS,Kenneth A. DNA methylation profiling: an emerging paradigm for cancer diagnosis[J]. Annu Rev Pathol, 2022, 17: 295-321.
[46]
Chen XQ,Zhang F, Su QC, et al. Methylome and transcriptome analyses reveal insights into the epigenetic basis for the good survival of hypomethylated ER-positive breast cancer subtype [ J ]. Clin Epigenetics, 2020, 12(1): 16.
[47]
Croes L,Beyens M, Fransen E, et al. Large-scale analysis of DFNA5 methylation reveals its potential as biomarker for breast cancer[J]. Clin Epigenetics, 2018, 10: 51.
[48]
Moss J,Zick A, Grinshpun A, et al. Circulating breast-derived DNA allows universal detection and monitoring of localized breast cancer[J].Ann Oncol, 2020, 31(3): 395-403.
[49]
Müller D,Gyorffy B. DNA methylation-based diagnostic, prognostic,and predictive biomarkers in colorectal cancer[J]. Biochim Biophys Acta Rev Cancer, 2022, 1877(3): 188722.
[50]
Stadler JC,Belloum Y, Deitert B, et al. Current and future clinical applications of ctDNA in immuno-oncology[J]. Cancer Res, 2022,82(3): 349-358.
[51]
Feng H,Jin P, Wu H. Disease prediction by cell-free DNA methylation[J]. Brief Bioinform, 2019, 20(2): 585-597.
[52]
Malla M,Loree JM, Kasi PM, et al. Using circulating tumor DNA in colorectal cancer: current and evolving practices[J]. J Clin Oncol,2022, 40(24): 2846-2857.
[53]
Wang B,Wang M, Lin Y, et al. Circulating tumor DNA methylation: a promising clinical tool for cancer diagnosis and management[J]. Clin Chem Lab Med, 2024, 62(11): 2111-2127.
[54]
Xu ZL,Sandler D, Taylor JA. Blood DNA methylation and breast cancer: a prospective case-cohort analysis in the sister study[J]. J Natl Cancer Inst, 2020, 112(1): 11-16.
[55]
Shan M,Yin H, Li J, et al. Detection of aberrant methylation of a sixgene panel in serum DNA for diagnosis of breast cancer [J].Oncotarget, 2016, 7(14): 18485-18494.
[56]
Hai L,Li L, Liu Z, et al. Whole-genome circulating tumor DNA methylation landscape reveals sensitive biomarkers of breast cancer[J].Med Comm, 2022, 3(3): e134.
[1] 李洋, 蔡金玉, 党晓智, 常婉英, 巨艳, 高毅, 宋宏萍. 基于深度学习的乳腺超声应变弹性图像生成模型的应用研究[J/OL]. 中华医学超声杂志(电子版), 2024, 21(06): 563-570.
[2] 王昭雨, 姜军. 乳腺癌外科治疗理论和技术的发展与挑战[J/OL]. 中华乳腺病杂志(电子版), 2025, 19(01): 1-5.
[3] 张群, 李俊杰. 乳腺癌外科十大热点[J/OL]. 中华乳腺病杂志(电子版), 2025, 19(01): 6-11.
[4] 徐航程, 王佳玉. PI3K/AKT/mTOR 信号通路及其靶向治疗在乳腺癌中的应用[J/OL]. 中华乳腺病杂志(电子版), 2025, 19(01): 12-19.
[5] 方婉婷, 商家炜, 孟英爽, 闫婷, 明健. 一步核酸扩增在乳腺癌前哨淋巴结转移检测中的应用[J/OL]. 中华乳腺病杂志(电子版), 2025, 19(01): 20-26.
[6] 王峰, 曲更宝, 王文彦, 代艳亭. 罗汉果醇对人乳腺癌细胞自噬和凋亡的影响[J/OL]. 中华乳腺病杂志(电子版), 2025, 19(01): 27-32.
[7] 李琳琳, 白雪, 赵海东, 梁曦, 李学璐. 21 基因复发风险评分在早期乳腺癌中的应用[J/OL]. 中华乳腺病杂志(电子版), 2025, 19(01): 33-38.
[8] 辛岗, 刘佳妮, 胡崇珠, 杨颖. HER-2 表达与HER-2 阳性乳腺癌临床病理特征及靶向治疗疗效的关系[J/OL]. 中华乳腺病杂志(电子版), 2025, 19(01): 45-48.
[9] 徐莹莹. 乳房手术的降阶处理[J/OL]. 中华乳腺病杂志(电子版), 2025, 19(01): 63-63.
[10] 杨汐, 李婷婷, 黄旭. 带蒂背阔肌皮瓣一期乳房重建术中腋窝区手术技巧[J/OL]. 中华乳腺病杂志(电子版), 2025, 19(01): 64-64.
[11] 苏明, 唐丹萍, 王萍, 何谦. 乳腺癌改良根治术后即刻乳房重建的方法选择研究进展[J/OL]. 中华普外科手术学杂志(电子版), 2025, 19(02): 231-234.
[12] 高杰红, 黎平平, 齐婧, 代引海. ETFA和CD34在乳腺癌中的表达及与临床病理参数和预后的关系研究[J/OL]. 中华普外科手术学杂志(电子版), 2025, 19(01): 64-67.
[13] 韩萌萌, 冯雪园, 马宁. 乳腺癌改良根治术后桡神经损伤1例[J/OL]. 中华普外科手术学杂志(电子版), 2025, 19(01): 117-118.
[14] 张志兆, 王睿, 郜苹苹, 王成方, 王成, 齐晓伟. DNMT3B与乳腺癌预后的关系及其生物学机制[J/OL]. 中华普外科手术学杂志(电子版), 2024, 18(06): 624-629.
[15] 孙晗, 于冰, 武侠, 周熙朗. 基于循环肿瘤DNA 甲基化的结直肠癌筛查预测模型的构建与验证[J/OL]. 中华消化病与影像杂志(电子版), 2024, 14(06): 500-506.
阅读次数
全文


摘要