ZMYND8在成人胶质瘤患者中的表达及其预后价值

doi:10.3969/j.issn.1004-616x.2025.01.009

摘要/Abstract

摘要： 目的：探讨锌指含髓样神经变性表皮生长因子结构域第8亚型(ZMYND8)在成人胶质瘤患者中的表达及其诊断和预后价值。方法：采用免疫组织化学法检测104例成人胶质瘤患者的胶质瘤组织中ZMYND8蛋白的表达水平，分析ZMYND8蛋白表达与胶质瘤患者临床病理特征之间的关系，用受试者工作特征(ROC)曲线预测效能，评估ZMYND8蛋白表达与胶质瘤预后的关系，采用Kaplan-Meier生存分析比较ZMYND8蛋白表达与成人脑胶质瘤患者总生存时间(OS)的关系。采用Cox回归多因素分析影响胶质瘤患者术后生存的因素。结果：免疫组织化学检测结果显示ZMYND8蛋白在胶质瘤组织中的表达高于正常脑组织(P<0.05)，高级别脑胶质瘤中的表达率明显高于低级别胶质瘤(P<0.05)。ZMYND8蛋白表达与病理分型、WHO分级相关(P<0.01)，与性别、年龄、肿瘤部位、肿瘤直径、Karnofsky(KPS)评分无明显相关关系(P>0.05)。Kaplan-Meier生存分析显示ZMYND8蛋白高表达组胶质瘤患者的OS显著短于低表达组(P<0.01)。多因素Cox回归分析显示年龄、WHO分级是胶质瘤OS的独立危险因素。结论： ZMYND8蛋白在成人胶质瘤患者中表达升高，与恶性程度及预后相关，可作为一种新的胶质瘤诊断和预后判断的潜在标志物。

关键词: 胶质瘤, WHO分级, 免疫组织化学, 锌指含髓样神经变性表皮生长因子结构域第8亚型, 预后

Abstract: OBJECTIVE： To investigate the expression and prognostic value of subtype 8 of the zinc finger domain containing myeloid neurodegenerative epidermal growth factor (ZMYND8) in adult glioma. METHODS： Immunohistochemistry was used to detect the expression level of ZMYND8 in 104 adult glioma tissues， and the relationship between ZMYND8 expression and prognosis of glioma patients was evaluated by receiver operating characteristic (ROC) curve prediction efficiency. Kaplan-Meier survival was used to analyze the relationship between ZMYND8 expression and overall survival (OS) of adult human glioma patients. Cox regression was used to analyze factors affecting the survival of patients with glioma after surgery. RESULTS： The immunohistochemical results showed that the expression of ZMYND8 protein in glioma was higher than that in normal brain tissue (P<0.05)，and the high expression rate in high-grade glioma was significantly higher than that in low-grade glioma (P<0.05). The expression of ZMYND8 was correlated with pathological classification and WHO grade (P<0.01)，but not with sex，age，tumor site，tumor diameter，and Karnofsky (KPS) score. Kaplan-Meier survival analysis showed that the OS of glioma patients with high expression of ZMYND8 was significantly lower than that of glioma patients with low expression (Log-rank P<0.01). Multivariate Cox regression analysis showed that age and WHO grade were independent factors of glioma OS. CONCLUSION： The expression of ZMYND8 was increased in adult glioma patients and the increase was related to the degree of malignancy and prognosis. Thus，ZMYND8 can be used as a potential marker for the diagnosis and prognosis of glioma.

Key words: adult glioma, WHO, immunohistochemistry, zinc finger MYND-type containing 8, prognosis

中图分类号:

R739.4

肖焕钦, 谢寿城, 钟莹, 罗文娟, 黄艳芳, 罗海燕, 余秋祝, 朱文标. ZMYND8在成人胶质瘤患者中的表达及其预后价值[J]. 癌变·畸变·突变, 2025, 37(1): 52-55,62.

XIAO Huanqin, XIE Shoucheng, ZHONG Ying, LUO Wenjuan, HUANG Yanfang, LUO Haiyan, YU Qiuzhu, ZHU Wenbiao. ZMYND8 as a novel diagnostic and prognostic biomarker for glioma[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2025, 37(1): 52-55,62.

参考文献

[1] HORBINSKI C, BERGER T, PACKER R J, et al. Clinical implications of the 2021 edition of the WHO classification of central nervous system tumours[J]. Nat Rev Neurol, 2022, 18(9): 515-529.
[2] LAPOINTE S, PERRY A, BUTOWSKI N A. Primary brain tumours in adults[J]. Lancet, 2018, 392(10145): 432-446.
[3] STURM D, PFISTER S M, JONES D T W. Pediatric gliomas: current concepts on diagnosis, biology, and clinical management[J]. J Clin Oncol, 2017, 35(21): 2370-2377.
[4] CHEN Y, TSAI Y H, TSENG S H. Regulation of ZMYND8 to treat cancer[J]. Molecules, 2021, 26(4): 1083.
[5] GONG F D, CHIU L Y, COX B, et al. Screen identifies bromodomain protein ZMYND8 in chromatin recognition of transcription-associated DNA damage that promotes homologous recombination[J]. Genes Dev, 2015, 29(2): 197-211.
[6] CHEN J W, HE Q M, WU P S, et al. ZMYND8 expression combined with pN and pM classification as a novel prognostic prediction model for colorectal cancer: based on TCGA and GEO database analysis[J]. Cancer Biomark, 2020, 28(2): 201-211.
[7] PAN Q, ZHONG S S, WANG H L, et al. The ZMYND8-regulated mevalonate pathway endows YAP-high intestinal cancer with metabolic vulnerability[J]. Mol Cell, 2021, 81(13): 2736-2751.e8.
[8] CHEN J W, LIU J, CHEN X T, et al. Low expression of ZMYND8 correlates with aggressive features and poor prognosis in nasopharyngeal carcinoma[J]. Cancer Manag Res, 2019, 11: 7835-7843.
[9] 李博伟, 王胜, 卓扬佳, 等. 锌指含髓样神经变形表皮生长因子结构域第8亚型作为糖皮质激素受体下游基因在前列腺癌组织的表达及临床意义[J]. 中华实验外科杂志, 2017, 34(8): 1405-1407.
[10] LOUIS D N, PERRY A, WESSELING P, et al. The 2021 WHO Classification of Tumors of the Central Nervous System: a summary[J]. Neuro Oncol, 2021, 23(8): 1231-1251.
[11] KANU O O, MEHTA A, DI C H, et al. Glioblastoma multiforme: a review of therapeutic targets[J]. Expert Opin Ther Targets, 2009, 13(6): 701-718.
[12] LARA-VELAZQUEZ M, AL-KHARBOOSH R, JEANNERET S, et al. Advances in brain tumor surgery for glioblastoma in adults[J]. Brain Sci, 2017, 7(12): 166.
[13] LUDWIG K, KORNBLUM H I. Molecular markers in glioma[J]. J Neurooncol, 2017, 134(3): 505-512.
[14] KUROYANAGI J, SHIMADA Y, ZHANG B B, et al. Zinc finger MYND-type containing 8 promotes tumour angiogenesis via induction of vascular endothelial growth factor-a expression[J]. FEBS Lett, 2014, 588(18): 3409-3416.
[15] LAI A Y, WADE P A. Cancer biology and NuRD: a multifaceted chromatin remodelling complex[J]. Nat Rev Cancer, 2011, 11: 588-596.
[16] 刘长兵, 姚丰, 牛多山, 等. 胃癌组织中ZMYND8蛋白的表达及临床病理学意义[J]. 承德医学院学报, 2020, 37(4): 271-275.
[17] SACHDEV S, DMELLO C, SONABEND A M. Radiosensitization of IDH-mutated gliomas through ZMYND8-a pathway to improved outcomes[J]. Clin Cancer Res, 2023, 29(9): 1648-1650.
[18] CARNEY S V, BANERJEE K, MUJEEB A, et al. Zinc finger MYND-type containing 8(ZMYND8) is epigenetically regulated in mutant isocitrate dehydrogenase 1(IDH1) glioma to promote radioresistance[J]. Clin Cancer Res, 2023, 29(9): 1763-1782.
[19] 朱文标, 卢善明, 李海南, 等. 联合IDH1、1p/19q和ATRX对胶质瘤分子分型的临床意义[J]. 南昌大学学报: 医学版, 2020, 60(4): 41-45.