子宫内膜癌的表观遗传学研究进展

doi:10.3760/cma.j.cn371439-20200703-00037

摘要/Abstract

摘要：

子宫内膜癌是女性生殖系统恶性肿瘤之一,晚期子宫内膜癌预后欠佳,如何提高中晚期子宫内膜癌患者的总生存率、改善预后仍然是临床难题之一。近年来,针对肿瘤基因改变的研究逐渐增多,表观遗传学机制已成为妇科肿瘤进展的重要因素之一。表观遗传学包含很多现象,已知的如DNA甲基化、微小RNA的表达和基因沉默、染色质重塑等,这些改变可能是肿瘤发生、发展的重要因素,有望成为肿瘤新的治疗靶点。随着未来对子宫内膜癌表观遗传学研究的深入,可能会找到新的靶向治疗位点并为子宫内膜癌的靶向治疗提供新的思路。

关键词: 子宫内膜肿瘤, DNA甲基化, 微RNAs

Abstract:

Endometrial cancer is one of the malignant tumors of female reproductive system. The prognosis of advanced endometrial cancer is poor. How to improve the overall survival rate and improve the prognosis of patients with advanced endometrial cancer is still one of the clinical problems. In recent years, the research on tumor gene changes is increasing gradually. Epigenetics is the study of genetic changes in gene expression without changing the nucleotide sequence of genes. Epigenetics includes many phenomena, such as DNA methylation, microRNA expression and gene silencing, chromatin remodeling. These changes may be important factors in the occurrence and development of tumors, and may become new therapeutic targets for tumors. With the study on epigenetics of endometrial cancer in the future, new therapeutic targets may be found. Meanwhile, those study may provide new ideas for targeted therapy of endometrial cancer.

Key words: Endometrial neoplasms, DNA methylation, MicroRNAs

邓波儿, 孔为民. 子宫内膜癌的表观遗传学研究进展[J]. 国际肿瘤学杂志, 2021, 48(3): 184-188.

Deng Bo'er, Kong Weimin. Epigenetic research progress of endometrial cancer[J]. Journal of International Oncology, 2021, 48(3): 184-188.

参考文献 33

[1]	Stampoliou A, Arapantoni-Dadioti P, Pavlakis K. Epigenetic mechanisms in endometrial cancer[J]. J BUON, 2016,21(2):301-306. pmid: 27273937
[2]	Morice P, Leary A, Creutzberg C, et al. Endometrial cancer[J]. Lancet, 2016,387(10023):1094-1108. DOI: 10.1016/S0140-6736(15)00130-0. pmid: 26354523
[3]	杨凤泊, 赵丽君, 徐游贵, 等. 子宫内膜癌组织错配修复基因MMR表达及其临床意义[J]. 现代妇产科进展, 2020,29(2):120-124, 129. DOI: 10.13283/j.cnki.xdfckjz.2020.02.009.
[4]	Schultz MD, He Y, Whitaker JW, et al. Human body epigenome maps reveal noncanonical DNA methylation variation[J]. Nature, 2015,523(7559):212-216. DOI: 10.1038/nature14465. pmid: 26030523
[5]	Huo X, Sun H, Cao D, et al. Identification of prognosis markers for endometrial cancer by integrated analysis of DNA methylation and RNA-Seq data[J]. Sci Rep, 2019,9(1):9924. DOI: 10.1038/s41598-019-46195-8. pmid: 31289358
[6]	范宇, 王南, 高原, 等. 基于DNA甲基化的散发性子宫内膜癌生物学标志物的荟萃分析[J]. 海南医学, 2020,31(3):379-388. DOI: 10.3969/j.issn.1003-6350.2020.03.031.
[7]	Trimarchi MP, Yan P, Groden J, et al. Identification of endometrial cancer methylation features using combined methylation analysis methods[J]. PLoS One, 2017,12(3):e0173242. DOI: 10.1371/journal.pone.0173242.
[8]	Kahn RM, Gordhandas S, Maddy BP, et al. Universal endometrial cancer tumor typing: how much has immunohistochemistry, microsa-tellite instability, and MLH1 methylation improved the diagnosis of Lynch syndrome across the population?[J]. Cancer, 2019,125(18):3172-3183. DOI: 10.1002/cncr.32203. pmid: 31150123
[9]	晋薇, 王利群, 刘有, 等. 子宫内膜组织中MMR蛋白表达及MLH1基因甲基化的临床意义[J]. 中华妇产科杂志, 2018,53(12):823-830. DOI: 10.3760/cma.j.issn.0529-567x.2018.12.005.
[10]	Kim J, Kong JK, Yang W, et al. DNA mismatch repair protein immunohistochemistry and MLH1 promotor methylation testing for practical molecular classification and the prediction of prognosis in endometrial cancer[J]. Cancers (Basel), 2018,10(9):279. DOI: 10.3390/cancers10090279.
[11]	Kim SR, Pina A, Albert A, et al. Does MMR status in endometrial cancer influence response to adjuvant therapy?[J]. Gynecol Oncol, 2018,151(1):76-81. DOI: 10.1016/j.ygyno.2018.08.020. pmid: 30172479
[12]	Green AK, Feinberg J, Makker V. A review of immune checkpoint blockade therapy in endometrial cancer[J]. Am Soc Clin Oncol Educ Book, 2020,40:1-7. DOI: 10.1200/EDBK_280503.
[13]	Le DT, Uram JN, Wang H, et al. PD-1 blockade in tumors with mismatch-repair deficiency[J]. N Engl J Med, 2015,372(26):2509-2520. DOI: 10.1056/NEJMoa1500596. doi: 10.1056/NEJMoa1500596 pmid: 26028255
[14]	Caplakova V, Babusikova E, Blahovcova E, et al. DNA methylation machinery in the endometrium and endometrial cancer[J]. Anticancer Res, 2016,36(9):4407-4420. DOI: 10.21873/anticanres.10984. pmid: 27630276
[15]	Fialkova V, Vidomanova E, Balharek T, et al. DNA methylation as mechanism of apoptotic resistance development in endometrial cancer patients[J]. Gen Physiol Biophys, 2017,36(5):521-529. DOI: 10.4149/gpb_2017032.
[16]	Wang H, Cui M, Zhang S, et al. Relationship between RAS association domain family protein 1A promoter methylation and the clinicopathological characteristics in patients with ovarian cancer: a syste-matic meta-analysis[J]. Gynecol Obstet Invest, 2018,83(4):349-357. DOI: 10.1159/000484245. pmid: 29130987
[17]	Pabalan N, Kunjantarachot A, Ruangpratheep C, et al. Potential of RASSF1A promoter methylation as biomarker for endometrial cancer: a systematic review and meta-analysis[J]. Gynecol Oncol, 2017,146(3):603-608. DOI: 10.1016/j.ygyno.2017.06.017.
[18]	黄丽萍, 陈晨, 王雪萍, 等. 5-Aza-CdR对子宫内膜癌中RASSF1A基因甲基化的作用[J]. 四川大学学报(医学版), 2015,46(3):380-383.
[19]	van der Putten LJM, van Hoof R, Tops BBJ, et al. Molecular profiles of benign and (pre)malignant endometrial lesions[J]. Carcinogenesis, 2017,38(3):329-335. DOI: 10.1093/carcin/bgx008. doi: 10.1093/carcin/bgx008 pmid: 28203752
[20]	Ghazanfari T, Asaadi Tehrani G, Maziri P. The relationship between the methylation of promoter regions of tumor suppressor genes PTEN and APC with endometrial cancer[J]. Asian Pac J Cancer Prev, 2019,20(8):2259-2265. DOI: 10.31557/APJCP.2019.20.8.2259.
[21]	Cornel KMC, Wouters K, Van de Vijver KK, et al. Gene promoter methylation in endometrial carcinogenesis[J]. Pathol Oncol Res, 2019,25(2):659-667. DOI: 10.1007/s12253-018-0489-2. doi: 10.1007/s12253-018-0489-2 pmid: 30430425
[22]	Deng X, Hou C, Wang H, et al. Hypermethylation of WIF1 and its inhibitory role in the tumor growth of endometrial adenocarcinoma[J]. Mol Med Rep, 2017,16(5):7497-7503. DOI: 10.3892/mmr.2017.7564. doi: 10.3892/mmr.2017.7564 pmid: 28944908
[23]	Onstad MA, Schmandt RE, Lu KH. Addressing the role of obesity in endometrial cancer risk, prevention, and treatment[J]. J Clin Oncol, 2016,34(35):4225-4230. DOI: 10.1200/JCO.2016.69.4638. doi: 10.1200/JCO.2016.69.4638 pmid: 27903150
[24]	Nagashima M, Miwa N, Hirasawa H, et al. Genome-wide DNA methylation analysis in obese women predicts an epigenetic signature for future endometrial cancer[J]. Sci Rep, 2019,9(1):6469. DOI: 10.1038/s41598-019-42840-4.
[25]	Tu C, Wang F, Wan J. MicroRNA-381 inhibits cell proliferation and invasion in endometrial carcinoma by targeting the IGF-1R[J]. Mol Med Rep, 2018,17(3):4090-4098. DOI: 10.3892/mmr.2017.8288. doi: 10.3892/mmr.2017.8288 pmid: 29257334
[26]	Yan H, Sun BM, Zhang YY, et al. Upregulation of miR-183-5p is responsible for the promotion of apoptosis and inhibition of the epithelial-mesenchymal transition, proliferation, invasion and migration of human endometrial cancer cells by downregulating Ezrin[J]. Int J Mol Med, 2018,42(5):2469-2480. DOI: 10.3892/ijmm.2018.3853. doi: 10.3892/ijmm.2018.3853 pmid: 30226564
[27]	Liu Y, Li H, Zhao C, et al. MicroRNA-101 inhibits angiogenesis via COX-2 in endometrial carcinoma[J]. Mol Cell Biochem, 2018,448(1-2):61-69. DOI: 10.1007/s11010-018-3313-0. pmid: 29404887
[28]	Sun X, Dongol S, Qiu C, et al. miR-652 promotes tumor proliferation and metastasis by targeting RORA in endometrial cancer[J]. Mol Cancer Res, 2018,16(12):1927-1939. DOI: 10.1158/1541-7786.MCR-18-0267. pmid: 30093563
[29]	Zhang W, Chen JH, Shan T, et al. miR-137 is a tumor suppressor in endometrial cancer and is repressed by DNA hypermethylation[J]. Lab Invest, 2018,98(11):1397-1407. DOI: 10.1038/s41374-018-0092-x. pmid: 29955087
[30]	Torres A, Kozak J, Korolczuk A, et al. Locked nucleic acid-inhibitor of miR-205 decreases endometrial cancer cells proliferation in vitro and in vivo[J]. Oncotarget, 2016,7(45):73651-73663. DOI: 10.18632/oncotarget.12043. pmid: 27655663
[31]	Takeda T, Banno K, Okawa R, et al. ARID1A gene mutation in ovarian and endometrial cancers (Review)[J]. Oncol Rep, 2016,35(2):607-613. DOI: 10.3892/or.2015.4421. doi: 10.3892/or.2015.4421 pmid: 26572704
[32]	Toumpeki C, Liberis A, Tsirkas I, et al. The role of ARID1A in endometrial cancer and the molecular pathways associated with pathogenesis and cancer progression[J]. In Vivo, 2019,33(3):659-667. DOI: 10.21873/invivo.11524. pmid: 31028182
[33]	Kim KH, Roberts CW. Targeting EZH2 in cancer[J]. Nat Med, 2016,22(2):128-134. DOI: 10.1038/nm.4036. doi: 10.1038/nm.4036 pmid: 26845405