儿童急性淋巴细胞白血病中E-钙黏蛋白甲基化对预后的影响

齐凤旗, 韩伟, 颜静, 辛聪, 李艳, 郭雷, 王文鹏, 高吉照

中国当代儿科杂志 ›› 2023, Vol. 25 ›› Issue (1) : 46-50.

PDF(676 KB)
HTML
PDF(676 KB)
HTML
中国当代儿科杂志 ›› 2023, Vol. 25 ›› Issue (1) : 46-50. DOI: 10.7499/j.issn.1008-8830.2208018
论著·临床研究

儿童急性淋巴细胞白血病中E-钙黏蛋白甲基化对预后的影响

  • 齐凤旗, 韩伟, 颜静, 辛聪, 李艳, 郭雷, 王文鹏, 高吉照
作者信息 +

Influence of E-cadherin methylation on prognosis in children with acute lymphoblastic leukemia

  • QI Feng-Qi, HAN Wei, YAN Jing, XIN Cong, LI Yan, GUO Lei, WANG Wen-Peng, GAO Ji-Zhao
Author information +
文章历史 +

摘要

目的 检测儿童急性淋巴细胞白血病(acute lymphoblastic leukemia,ALL)患儿骨髓单个核细胞中E-钙黏蛋白(E-cadherin)mRNA及蛋白水平表达和基因甲基化状态,探讨E-cadherin在儿童ALL的意义及甲基化状态与预后的关系。 方法 采集42例初次确诊的ALL患儿确诊时(治疗前组)及诱导化疗第33天(治疗后组)的骨髓血5 mL,应用RT-qPCR、Westerm blot及甲基化特异性PCR法检测骨髓单个核细胞中E-cadherin mRNA及蛋白表达和E-cadherin基因甲基化水平,并比较治疗前后各指标的变化。 结果 治疗后组E-cadherin mRNA及蛋白的表达水平均高于治疗前组(P<0.05);治疗后组E-cadherin基因甲基化阳性率较治疗前组下降(P<0.05);至试验终点时,甲基化阴性者总生存率和无事件生存率均高于甲基化阳性者(P<0.05)。 结论 E-cadherin表达与儿童ALL发展相关,表达降低及甲基化水平增高可能提示预后不良。

Abstract

Objective To study the significance of E-cadherin and the association between E-cadherin methylation status and prognosis in children with acute lymphoblastic leukemia (ALL) by examining the mRNA and protein expression of E-cadherin and its gene methylation status in bone marrow mononuclear cells of children with ALL. Methods The samples of 5 mL bone marrow blood were collected from 42 children with ALL who were diagnosed for the first time at diagnosis (pre-treatment group) and on day 33 of induction chemotherapy (post-treatment group). RT-qPCR, Western blot, and methylation-specific PCR were used to measure the mRNA and protein expression of E-cadherin and the methylation level of the E-cadherin gene. The changes in each index after induction chemotherapy were compared. Results The mRNA and protein expression levels of E-cadherin in the post-treatment group were significantly higher than those in the pre-treatment group (P<0.05), while the positive rate of E-cadherin gene methylation in the post-treatment group was significantly lower than that in the pre-treatment group (P<0.05). At the end of the test, the children with negative methylation had significantly higher overall survival rate and event-free survival rate than those with positive methylation (P<0.05). Conclusions E-cadherin expression is associated with the development of ALL in children, and its decreased expression and increased methylation level may indicate a poor prognosis.

关键词

急性淋巴细胞白血病 / E-钙黏蛋白 / 甲基化 / 预后 / 儿童

Key words

Acute lymphoblastic leukemia / E-cadherin / Methylation / Prognosis / Child

引用本文

导出引用
齐凤旗, 韩伟, 颜静, 辛聪, 李艳, 郭雷, 王文鹏, 高吉照. 儿童急性淋巴细胞白血病中E-钙黏蛋白甲基化对预后的影响[J]. 中国当代儿科杂志. 2023, 25(1): 46-50 https://doi.org/10.7499/j.issn.1008-8830.2208018
QI Feng-Qi, HAN Wei, YAN Jing, XIN Cong, LI Yan, GUO Lei, WANG Wen-Peng, GAO Ji-Zhao. Influence of E-cadherin methylation on prognosis in children with acute lymphoblastic leukemia[J]. Chinese Journal of Contemporary Pediatrics. 2023, 25(1): 46-50 https://doi.org/10.7499/j.issn.1008-8830.2208018

参考文献

1 Chang JH, Poppe MM, Hua CH, et al. Acute lymphoblastic leukemia[J]. Pediatr Blood Cancer, 2021, 68Suppl 2:e28371. PMID: 33818880. DOI: 10.1002/pbc.28371.
2 Kontomanolis EN, Koutras A, Syllaios A, et al. Role of oncogenes and tumor-suppressor genes in carcinogenesis: a review[J]. Anticancer Res, 2020, 40(11): 6009-6015. PMID: 33109539. DOI: 10.21873/anticanres.14622.
3 Loh CY, Chai JY, Tang TF, et al. The E-cadherin and N-cadherin switch in epithelial-to-mesenchymal transition: signaling, therapeutic implications, and challenges[J]. Cells, 2019, 8(10): 1118. PMID: 31547193. PMCID: PMC6830116. DOI: 10.3390/cells8101118.
4 Corso G, Figueiredo J, De Angelis SP, et al. E-cadherin deregulation in breast cancer[J]. J Cell Mol Med, 2020, 24(11): 5930-5936. PMID: 32301282. PMCID: PMC7294130. DOI: 10.1111/jcmm.15140.
5 Zhou C, Yang C, Chong D. E-cadherin expression is associated with susceptibility and clinicopathological characteristics of thyroid cancer: a PRISMA-compliant meta-analysis[J]. Medicine (Baltimore), 2019, 98(30): e16187. PMID: 31348230. PMCID: PMC6709073. DOI: 10.1097/MD.0000000000016187.
6 Ye CC, Wang J. E-cadherin (CDH1) gene -160C/A polymorphism and the risk of colorectal cancer: a meta-analysis involving 17,291 subjects[J]. J Gene Med, 2021, 23(10): e3370. PMID: 34097324. DOI: 10.1002/jgm.3370.
7 Abdullah M, Choo CW, Alias H, et al. ADAMTSL5 and CDH11: putative epigenetic markers for therapeutic resistance in acute lymphoblastic leukemia[J]. Hematology, 2017, 22(7): 386-391. PMID: 28292214. DOI: 10.1080/10245332.2017.1299417.
8 中华医学会儿科学分会血液学组, 《中华儿科杂志》编辑委员会. 儿童急性淋巴细胞白血病诊疗建议(第四次修订)[J]. 中华儿科杂志, 2014, 52(9): 641-644. DOI: 10.3760/cma.j.issn.0578-1310.2014.09.001.
9 Bure IV, Nemtsova MV, Zaletaev DV. Roles of E-cadherin and noncoding RNAs in the epithelial-mesenchymal transition and progression in gastric cancer[J]. Int J Mol Sci, 2019, 20(12): 2870. PMID: 31212809. PMCID: PMC6627057. DOI: 10.3390/ijms20122870.
10 Zhu X, Wang X, Gong Y, et al. E-cadherin on epithelial-mesenchymal transition in thyroid cancer[J]. Cancer Cell Int, 2021, 21(1): 695. PMID: 34930256. PMCID: PMC8690896. DOI: 10.1186/s12935-021-02344-6.
11 Zhao H, Hu H, Chen B, et al. Overview on the role of E-cadherin in gastric cancer: dysregulation and clinical implications[J]. Front Mol Biosci, 2021, 8: 689139. PMID: 34422902. PMCID: PMC8371966. DOI: 10.3389/fmolb.2021.689139.
12 高吉照, 谭英, 赵继鸥, 等. 儿童急性淋巴细胞白血病E-cadherin表达及与临床指标相关性分析[J]. 中国小儿血液与肿瘤杂志, 2018, 23(2): 74-78. DOI: 10.3969/j.issn.1673-5323.2018.02.004.
13 Katoh M. Multi?layered prevention and treatment of chronic inflammation, organ fibrosis and cancer associated with canonical WNT/β?catenin signaling activation (review)[J]. Int J Mol Med, 2018, 42(2): 713-725. PMID: 29786110. PMCID: PMC6034925. DOI: 10.3892/ijmm.2018.3689.
14 Nguyen VHL, Hough R, Bernaudo S, et al. Wnt/β-catenin signalling in ovarian cancer: insights into its hyperactivation and function in tumorigenesis[J]. J Ovarian Res, 2019, 12(1): 122. PMID: 31829231. PMCID: PMC6905042. DOI: 10.1186/s13048-019-0596-z.
15 Wong KK. DNMT1 as a therapeutic target in pancreatic cancer: mechanisms and clinical implications[J]. Cell Oncol (Dordr), 2020, 43(5): 779-792. PMID: 32504382. DOI: 10.1007/s13402-020-00526-4.
16 McCormick TM, Canedo NH, Furtado YL, et al. Association between human papillomavirus and Epstein-Barr virus DNA and gene promoter methylation of RB1 and CDH1 in the cervical lesions: a transversal study[J]. Diagn Pathol, 2015, 10: 59. PMID: 26032781. PMCID: PMC4450846. DOI: 10.1186/s13000-015-0283-3.
17 Skvortsova K, Stirzaker C, Taberlay P. The DNA methylation landscape in cancer[J]. Essays Biochem, 2019, 63(6): 797-811. PMID: 31845735. PMCID: PMC6923322. DOI: 10.1042/EBC20190037.
18 罗静, 马梁明, 侯翠芳, 等. 地西他滨联合柔红霉素对HL-60细胞增殖及PTEN基因表达的影响[J]. 中华血液学杂志, 2012, 33(6): 486-488. DOI: 10.3760/cma.j.issn.0253-2727.2012.06.015.
19 Wong SHM, Fang CM, Chuah LH, et al. E-cadherin: its dysregulation in carcinogenesis and clinical implications[J]. Crit Rev Oncol Hematol, 2018, 121: 11-22. PMID: 29279096. DOI: 10.1016/j.critrevonc.2017.11.010.

PDF(676 KB)
HTML

Accesses

Citation

Detail

段落导航
相关文章

/