国际肿瘤学杂志

国际肿瘤学杂志 ›› 2019, Vol. 46 ›› Issue (9): 519-525.doi: 10.3760/cma.j.issn.1673-422X.2019.09.002

• 论著 • 上一篇    下一篇

LSD1、MGMT和Ki-67在高级别胶质瘤中的表达及对预后的影响

张千慧,张洋,宿伟鹏,张宋安,刘攀,赵化荣   

  1. 新疆医科大学第一附属医院肿瘤中心，乌鲁木齐830000
  • 收稿日期:2018-12-06 出版日期:2019-09-08 发布日期:2019-09-08
  • 通讯作者: 赵化荣 E-mail:xydyfyzhr@163.com
  • 基金资助:
    新疆维吾尔自治区自然科学基金（2016D01C263）

Expressions of LSD1, MGMT and Ki-67 in high-grade glioma and their influences on prognosis

Zhang Qianhui, Zhang Yang, Su Weipeng, Zhang Song′an, Liu Pan, Zhao Huarong   

  1. Cancer Center, First Affiliated Hospital of Xinjiang Medical University, Urumqi 830000, China
  • Received:2018-12-06 Online:2019-09-08 Published:2019-09-08
  • Contact: Zhao Huarong E-mail:xydyfyzhr@163.com
  • Supported by:
    Natural Science Foundation of Xinjiang Uygur Autonomous Region (2016D01C263)

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摘要： 目的 探讨组蛋白赖氨酸特异性去甲基化酶1（LSD1）、O6-甲基鸟嘌呤DNA甲基转移酶（MGMT）、细胞增殖相关抗原Ki-67在高级别胶质瘤中的表达及其对预后的影响。方法选取新疆医科大学第一附属医院2011年1月至2017年6月经病理证实的Ⅲ、Ⅳ级胶质瘤标本65例，采用免疫组织化学（SP法）检测病理标本中LSD1、MGMT和Ki-67蛋白的表达情况，通过长期随访评价治疗效果，分析3种标志物与患者病理分级、无进展生存期（PFS）、总生存期（OS）的关系。结果 65例高级别胶质瘤标本中，LSD1、MGMT、Ki-67总体阳性表达率分别为70.8%（46/65）、60.0%（39/65）、100%（65/65）。LSD1和MGMT在Ⅲ、Ⅳ级胶质瘤中的表达差异无统计学意义（χ2=1.588，P=0.208；χ2=0.013，P=0.908）。Ⅳ级胶质瘤中Ki67表达（+）、（++）、（+++）分别为18、19、11例，Ⅲ级胶质瘤中Ki67表达（+）、（++）、（+++）分别为11、5、1例，两者表达强度差异有统计学意义（Z=-2.083，P=0.037）。logrank检验表明，LSD1、MGMT的阳性表达及Ki67不同程度的阳性表达均与高级别胶质瘤患者PFS呈负相关（χ2=12.217，P=0.007；χ2=4.446，P=0.035；χ2=12.536，P=0.002），也与OS呈负相关（χ2=11.708，P=0.008；χ2=6.637，P=0.010；χ2=11.807，P=0.003）。病理分级为Ⅳ级的患者较Ⅲ级患者更容易出现疾病局部进展（χ2=6.573，P=0.010），且OS短（χ2=3.974，P=0.046）。Cox比例风险模型分析结果提示，LSD1表达（HR=1.361，95%CI为1.094～1.694，P=0.006；HR=1.406，95%CI为1.117～1.771，P=0.004）和Ki67表达（HR=1.703，95%CI为1.175～2.468，P=0.005；HR=1.778，95%CI为1.209～2.616，P=0.003）是高级别胶质瘤患者PFS和OS的独立预后风险因子。相关分析结果显示，MGMT与LSD1的表达呈正相关（r=0.406，P=0.001）。结论LSD1、MGMT、Ki67在高级别胶质瘤中总体阳性表达率较高，MGMT为高级别胶质瘤预后相关因素，LSD1、Ki67可作为高级别胶质瘤预后的独立预测指标。

关键词: 神经胶质瘤, O(6)-甲基鸟嘌呤DNA甲基转移酶, Ki-67抗原, 预后, 赖氨酸特异性去甲基化酶1

Abstract: Objective To investigate the expressions of histone lysine-specific demethylase 1 (LSD1), O6-methylguanine DNA methyltransferase (MGMT) and cell proliferationassociated antigen Ki-67 in high-grade glioma and their influences on prognosis. Methods Sixty-five cases of grade Ⅲ and Ⅳ glioma confirmed by pathology from January 2011 to June 2017 in the First Affiliated Hospital of Xinjiang Medical University were selected. Immunohistochemistry (SP method) was used to detect the expressions of LSD1, MGMT and Ki-67 in pathological specimens. The therapeutic effect was evaluated by long-term follow-up. The relationships between the three markers and pathological grade, progression-free survival (PFS) and overall survival (OS) were analyzed. Results The overall positive rates of LSD1, MGMT and Ki-67 in the 65 highgrade glioma specimens were 70.8% (46/65), 60.0% (39/65) and 100.0% (65/65), respectively. There were no significant differences in the expressions of LSD1 and MGMT in grade Ⅲ and Ⅳ glioma (χ2=1.588, P=0.208, χ2=0.013, P=0.908). Ki-67 expression (+), (++), (+++) in grade Ⅳ glioma were observed in 18, 19 and 11 cases, respectively. Ki67 expression (+), (++) in grade Ⅲ glioma were observed in 11, 5 cases, and 1 case was (+++), and the difference in expression intensity between the two groups was statistically significant (Z=-2.083, P=0.037). Log-rank test showed that the positive expressions of LSD1, MGMT and Ki67 were negatively correlated with the PFS of patients with highgrade glioma (χ2=12.217, P=0.007; χ2=4.446, P=0.035; χ2=12.536, P=0.002), also were negatively correlated with OS (χ2=11.708, P=0.008; χ2=6.637, P=0.010; χ2=11.807, P=0.003). Grade Ⅳ patients were more likely to have relapse progression than grade Ⅲ patients (χ2=6.573, P=0.010), and OS was shorter (χ2=3.974, P=0.046). Cox proportional hazards model analysis showed that the expressions of LSD1 (HR=1.361, 95%CI: 1.094-1.694, P=0.006; HR=1.406, 95%CI: 1.117-1.771, P=0.004) and Ki-67 (HR=1.703, 95%CI: 1.175-2.468, P=0.005; HR=1.778, 95%CI: 1.209-2.616, P=0.003) were the independent prognostic risk factors for PFS and OS of patients with high-grade glioma. Correlation analysis results showed that the expression of MGMT was positively correlated with the expression of LSD1 (r=0.406, P=0.001). Conclusion LSD1, MGMT and Ki-67 have higher positive expression rates in high-grade glioma. MGMT is a prognostic factor for highgrade glioma, and LSD1 and Ki-67 can be used as independent predictors of prognosis for high-grade gliomas.

Key words: Glioma, O(6) -methylguanine DNA methyltransferase, Ki-67 antigen, Prognosis, Lysine specific demethylase 1